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Background: Current treatment recommendations for patients with heart failure and secondary mitral regurgitation include transcatheter edge-to-edge repair and mitral-valve surgery. Data from randomized trials comparing these therapies are lacking in this patient population., Methods: In this noninferiority trial conducted in Germany, patients with heart failure and secondary mitral regurgitation who continued to have symptoms despite guideline-directed medical therapy were randomly assigned, in a 1:1 ratio, to undergo either transcatheter edge-to-edge repair (intervention group) or surgical mitral-valve repair or replacement (surgery group). The primary efficacy end point was a composite of death, hospitalization for heart failure, mitral-valve reintervention, implantation of an assist device, or stroke within 1 year after the procedure. The primary safety end point was a composite of major adverse events within 30 days after the procedure., Results: A total of 210 patients underwent randomization. The mean (±SD) age of the patients was 70.5±7.9 years, 39.9% were women, and the mean left ventricular ejection fraction was 43.0±11.7%. Within 1 year, at least one of the components of the primary efficacy end point occurred in 16 of the 96 patients with available data (16.7%) in the intervention group and in 20 of the 89 with available data (22.5%) in the surgery group (estimated mean difference, -6 percentage points; 95% confidence interval [CI], -17 to 6; P<0.001 for noninferiority). A primary safety end-point event occurred in 15 of the 101 patients with available data (14.9%) in the intervention group and in 51 of the 93 patients with available data (54.8%) in the surgery group (estimated mean difference, -40 percentage points; 95% CI, -51 to -27; P<0.001)., Conclusions: Among patients with heart failure and secondary mitral regurgitation, transcatheter edge-to-edge repair was noninferior to mitral-valve surgery with respect to a composite of death, rehospitalization for heart failure, stroke, reintervention, or implantation of an assist device in the left ventricle at 1 year. (Funded by Abbott Vascular; MATTERHORN ClinicalTrials.gov number, NCT02371512.)., (Copyright © 2024 Massachusetts Medical Society.)

Aims: Non-ischaemic cardiomyopathy (NICMP), an incurable disease terminating in systolic heart failure (heart failure with reduced ejection fraction [HFrEF]), causes immune activation, however anti-inflammatory treatment strategies so far have failed to alter the course of this disease. Myeloperoxidase (MPO), the principal enzyme in neutrophils, has cytotoxic, pro-fibrotic and nitric oxide oxidizing effects. Whether MPO inhibition ameliorates the phenotype in NICMP remains elusive., Methods and Results: Prognostic information from MPO was derived from proteomic data of a large human cardiovascular health cohort (n = 3289). In a murine model of NICMP, we studied the mechanisms of MPO in this disease. In a case series, the MPO inhibitor was also evaluated in NICMP patients. Individuals with increased MPO revealed higher long-term mortality and worsening of heart failure, with impaired prognosis when MPO increased during follow-up. MPO infusion attenuated left ventricular ejection fraction (LVEF) in mice with NICMP, whereas genetic ablation or inhibition of MPO decreased systemic vascular resistance (SVR, 9.4 ± 0.7 mmHg*min/ml in NICMP vs. 6.7 ± 0.8 mmHg*min/ml in NICMP/Mpo -/- mice, n = 8, p = 0.006, data expressed as mean ± standard error of the mean) and improved left ventricular function (LVEF 30.3 ± 2.2% in NICMP vs. 40.7 ± 1.1% in NICMP/Mpo -/- mice, n = 16, p < 0.0001). Four patients diagnosed with NICMP and treated with an MPO inhibitor over 12 weeks showed increase in LVEF, decline in natriuretic peptides and improved 6-min walking distance. MPO inhibitor-related changes in the proteome of NICMP patients predicted reduced mortality when related to the changes in the proteome of the above referenced cardiovascular health cohort., Conclusions: Myeloperoxidase predicts long-term outcome in HFrEF and its inhibition elicits systemic anti-inflammatory and vasodilating effects which translate into improved left ventricular function. MPO inhibition deserves further evaluation as a novel, complementary treatment strategy for HFrEF., (© 2024 The Author(s). European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Competing Interests: Funding Support and Author Disclosures Dr von Stein has received speaker honoraria and travel expenses by Edwards Lifesciences. Dr Iliadis has received travel support by Abbott and Edwards Lifesciences and consultant honoraria by Abbott and Edwards Lifesciences. Dr Baldus has received honorarium for consultation by Abbott and Edwards Lifesciences. Dr Pfister has received speaker fees by Edwards Lifesciences and Abbott.

Background: We assessed the efficacy and safety of tadalafil, a phosphodiesterase type 5 inhibitor, in patients with heart failure with preserved ejection fraction and combined postcapillary and precapillary pulmonary hypertension., Methods: In the double-blind PASSION study (Phosphodiesterase-5 Inhibition in Patients With Heart Failure With Preserved Ejection Fraction and Combined Post- and Pre-Capillary Pulmonary Hypertension), patients with heart failure with preserved ejection fraction and combined postcapillary and precapillary pulmonary hypertension were randomized 1:1 to receive tadalafil at a target dose of 40 mg or placebo. The primary end point was the time to the first composite event of adjudicated heart failure hospitalization or all-cause death. Secondary end points included all-cause mortality and improvements in New York Heart Association functional class or ≥10% improvement in 6-minute walking distance from baseline., Results: Initially targeting 372 patients, the study was terminated early because of disruption in study medication supply. At that point, 125 patients had been randomized (placebo: 63; tadalafil: 62,). Combined primary end-point events occurred in 20 patients (32%) assigned to placebo and 17 patients (27%) assigned to tadalafil (hazard ratio, 1.02 [95% CI, 0.52-2.01]; P =0.95). There was a possible signal of higher all-cause mortality in the tadalafil group (hazard ratio, 5.10 [95% CI, 1.10-23.69]; P =0.04). No significant between-group differences were observed in other secondary end points. Serious adverse events occurred in 29 participants (48%) in the tadalafil group and 35 (56%) in the placebo group., Conclusions: The PASSION trial, terminated prematurely due to study medication supply disruption, does not support tadalafil use in patients with heart failure with preserved ejection fraction and combined postcapillary and precapillary pulmonary hypertension, with potential safety concerns and no observed benefits in primary and secondary end points., Registration: URL: https://www.clinicaltrialsregister.eu/; Unique identifier: 2017-003688-37. URL: https://drks.de; Unique identifier: DRKS -DRKS00014595., Competing Interests: Dr Hoeper has received fees for lectures and/or consultations from Acceleron, Actelion, AOP Health, Bayer, Ferrer, GossamerBio, Janssen, Keros, and MSD. Max Wissmüller has received lecture fees from Janssen. Hanno Leuchte has received fees for consultations and/or lectures from Acceleron, Jansse-Cilag, Bayer, Boehringer-Ingelheim, Ferrer, MSD, and Pfizer. Michael Halank has received fees for lectures and/or consultations from AstraZeneca, Janssen-Cilag, and MSD. In addition, he has received support for attending meetings and/or travel from AOP Health and Janssen-Cilag. Hans-Jürgen Seyfarth has received fees for lectures and/or consultations from Janssen-Cilag and MSD. Stephan Baldus has received fees for lectures and/or consultations from Abbott, Edwards, Jenavalve, AstraZeneca, Bayer, Daiicho Sankyo, and Amgen, as well as research grants from Abbott, AstraZeneca, and Daiichi Sankyo. Johann Bauersachs has received fees for lectures and/or consultations from Amgen, AstraZeneca, Bayer, BMS, Boehringer Ingelheim, Cardior, Corvia, CVRx, Edwards, Norgine, Novartis, Pfizer, Roche and Vifor. In addition, institutional grants have been provided by Abiomed, CVRx, Norgine, Roche, and Zoll. He holds patents for microRNA and downstream targets for diagnostics and therapeutic purposes (PCT/EP2007/008772 and PCT/EP2009/051986). Michael Böhm is supported by the Deutsche Forschungsgemeinschaft (German Research Foundation; TTR 219, project No. 322900939) and reports personal fees from Abbott, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Cytokinetics, Medtronic, Novartis, ReCor, Servier and Vifor. Hossein-Ardeschir Ghofrani has received honoraria for consultations and/or speaking at conferences from Bayer HealthCare AG, Actelion, Encysive, Pfizer, Ergonex, Lilly, and Novartis. He is member of the Advisory Board for Acceleron, Bayer HealthCare AG, Pfizer, GSK, Actelion, Lilly, Merck, Encysive, and Ergonex. He has also received governmental grants from the German Research Foundation, Excellence Cluster Cardiopulmonary Research, State Government of Hessen, and the German Ministry for Education and Research. Stavros Konstantinides reports personal lecture/advisory fees and research grants to his institution from Bayer AG, Boston Scientific, Daiichi-Sankyo, LumiraDx, and Penumbra, as well as personal lecture/advisory fees from MSD and Pfizer–Bristol-Myers Squibb. Karen M. Olsson has received fees for lectures and/or consultations from Acceleron, Actelion, Bayer, Ferrer, GSK, Janssen, MSD, Pfizer, and United Therapeutics. Rolf Wachter has received fees for lectures and/or consultation from AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi Sankyo, Medtronic, Novartis, Pfizer, Pharmacosmo, Sciarc, Servier, and Vifor. His institution has received research grants from Deutsche Forschungsgemeinschaft, Bundesministerium für Bildung und Forschung, European Union, and Medtronic. Carolyn S.P. Lam is supported by a Clinician Scientist Award from the National Medical Research Council of Singapore; has received research support from NovoNordisk and Roche Diagnostics; has served as consultant or on the Advisory Board/ Steering Committee/ Executive Committee for Alleviant Medical, Allysta Pharma, AnaCardio AB, Applied Therapeutics, AstraZeneca, Bayer, Biopeutics, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb, CardioRenal, Cytokinetics, Darma Inc, EchoNous Inc, Eli Lilly, Impulse Dynamics, Intellia Therapeutics, Ionis Pharmaceutical, Janssen Research & Development LLC, Medscape/WebMD Global LLC, Merck, Novartis, Novo Nordisk, Prosciento Inc, Quidel Corp, Radcliffe Group Ltd, Recardio Inc, ReCor Medical, Roche Diagnostics, Sanofi, Siemens Healthcare Diagnostics, and Us2.ai; and serves as cofounder and non–executive director of Us2.ai. Stephan Rosenkranz has received fees for lectures and/or consultations from Abbott, Acceleron, Actelion, Aerovate, AOP, AstraZeneca, Bayer, Boehringer-Ingelheim, Edwards, Ferrer, Gossamer, Janssen, MSD, and United Therapeutics. His institution has received research grants from Actelion, AstraZeneca, Bayer, Janssen, and Lempo. The other authors report no conflicts.

Background: Two subtypes of atrial functional mitral regurgitation (AFMR) have been described, one is characterized by Carpentier type I and the other by Carpentier type IIIb leaflet motion., Objectives: The authors sought to analyze echocardiographic characteristics and outcomes of AFMR subtypes undergoing mitral valve transcatheter edge-to-edge repair (M-TEER)., Methods: Of 1,047 consecutive patients who underwent M-TEER, the authors identified those with isolated mitral annulus dilation (Carpentier I), termed AFMR-IAD, and those with atriogenic hamstringing characterized by restricted posterior mitral leaflet motion (Carpentier IIIb), termed AFMR-AH. Echocardiographic baseline characteristics and outcomes up to 1-year were analyzed., Results: A total of 128 patients (12.2%) met AFMR criteria; 75 (58.6%) were identified as AFMR-IAD and 53 (41.4%) as AFMR-AH. AFMR-AH displayed greater left atrial and left ventricular volumes, greater mitral annulus, shorter and steeper posterior mitral leaflet, and more pronounced MR (all P < 0.05). Technical success was achieved in 98.7% (AFMR-IAD) and 86.8% (AFMR-AH) of patients (P = 0.009). At discharge, device detachments were exclusively observed in AFMR-AH (10.0%). MR ≤II was achieved in 95.6% and 78.6% at 30 days (P = 0.009) and in 93.0% and 74.1% at 1 year (P = 0.038) in patients with AFMR-IAD and AFMR-AH, respectively. AFMR-AH was associated with procedural failure (OR: 1.17 [95% CI: 1.00-1.38]; P = 0.045) at 30 days (43.4% vs 24.0%; P = 0.023) and all-cause mortality (HR: 2.54 [95% CI: 1.09-5.91]; P = 0.031) at 1 year (77% vs 92%, Kaplan-Meier estimated 1-year survival; P = 0.017)., Conclusions: AFMR-AH shows worse procedural and clinical outcomes following M-TEER than AFMR-IAD. Thus, vigilance regarding this pathology is warranted and alternative mitral valve therapies might need to be considered., Competing Interests: Funding Support and Author Disclosures Dr J von Stein has received lecture fees from Edwards Lifesciences. Dr Körber has received travel support from JenaValve; and lecture fees from Edwards Lifesciences and Abbott. Dr Baldus has received consulting fees from Edwards Lifesciences. Dr Pfister has received speaker fees from Edwards Lifesciences and Abbott. Dr Hahn has received speaker fees from Abbott Structural, Baylis Medical, Edwards Lifesciences, Medtronic, Philips Healthcare, and Siemens Healthineers; holds institutional consulting contracts, for which she receives no direct compensation, with Abbott Structural, Anteris, Edwards Lifesciences, Medtronic, and Novartis; and is Chief Scientific Officer for the Echocardiography Core Laboratory at the Cardiovascular Research Foundation for multiple industry-sponsored valve trials, for which she receives no direct industry compensation. Dr Iliadis has received travel support and consulting fees from Abbott and Edwards Lifesciences. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Fibromas are rare primary benign cardiac tumours that can become symptomatic due to expansive growth, ventricular rhythm disturbances, and sudden cardiac death. Distinguishing fibromas from other (malign) cardiac masses is essential for accurate diagnosis and treatment. While there is some experience in management of cardiac fibromas in children, management of adult patients is unknown., Case Summary: We present three cases of cardiac fibroma in adult patients diagnosed by echocardiography, cardiovascular magnetic resonance (CMR), and computed tomography (CT): (1) a 55-year-old male with a left ventricular fibroma leading to reduced left ventricular ejection fraction and mitral regurgitation. He had family history of sudden cardiac death, showed premature ventricular contractions (PVCs), and was treated with a primary preventive subcutaneous implantable cardiac defibrillator (S-ICD); (2) a 39-year-old male with right ventricular fibroma as an incidental finding. He complained of episodes of PVC. Due to a low PVC burden, decision was made against ablation and the patient was planned for follow-up; and (3) an 18-year-old female with left ventricular apex fibroma detected by CMR shortly after birth and confirmed by surgical biopsy. Being asymptomatic, conservative management was pursued and follow-up by CMR planned., Discussion: Cardiac fibromas can show various clinical presentations and hence being detected late in life. Given potential complications of surgical biopsy, diagnosis of cardiac fibromas is primarily based on echocardiography, CT, and CMR. Rhythm disturbances as PVCs are common. Due to association with ventricular arrhythmias and sudden cardiac death, preventive ICD placement might be appropriate on an individual basis., Competing Interests: Conflict of interest: D.M.: speaker’s bureau, Philips Healthcare. L.P.: speaker’s bureau, Philips Healthcare; speaker’s bureau, Guerbet GmbH. The remaining authors disclose no relevant relationships., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Coronary artery disease (CAD) and severe aortic valve stenosis (AS) frequently coexist. While pre-transcatheter aortic valve replacement (TAVR) computed tomography angiography (CTA) allows to rule out obstructive CAD, interpreting hemodynamic significance of intermediate stenoses is challenging. This study investigates the incremental value of CT-derived fractional flow reserve (CT-FFR), quantitative coronary plaque characteristics (e.g., stenosis degree, plaque volume, and composition), and peri-coronary adipose tissue (PCAT) density to detect hemodynamically significant lesions among those with AS and CAD., Materials and Methods: We included patients with severe AS and intermediate coronary lesions (20-80% diameter stenosis) who underwent pre-TAVR CTA and invasive coronary angiogram (ICA) with resting full-cycle ratio (RFR) assessment between 08/16 and 04/22. CTA image analysis included assessment of CT-FFR, quantitative coronary plaque analysis, and PCAT density. Coronary lesions with RFR ≤ 0.89 indicated hemodynamic significance as reference standard., Results: Overall, 87 patients (age 77.9 ± 7.4 years, 38% female) with 95 intermediate coronary artery lesions were included. CT-FFR showed good discriminatory capacity (area under receiver operator curve (AUC) = 0.89, 95% confidence interval (CI) 0.81-0.96, p < 0.001) to identify hemodynamically significant lesions, superior to anatomical assessment, plaque morphology, and PCAT density. Plaque composition and PCAT density did not differ between lesions with and without hemodynamic significance. Univariable and multivariable analyses revealed CT-FFR as the only predictor for functionally significant lesions (odds ratio 1.28 (95% CI 1.17-1.43), p < 0.001). Overall, CT-FFR ≤ 0.80 showed diagnostic accuracy, sensitivity, and specificity of 88.4% (95%CI 80.2-94.1), 78.5% (95%CI 63.2-89.7), and 96.2% (95%CI 87.0-99.5), respectively., Conclusion: CT-FFR was superior to CT anatomical, plaque morphology, and PCAT assessment to detect functionally significant stenoses in patients with severe AS., Clinical Relevance Statement: CT-derived fractional flow reserve in patients with severe aortic valve stenosis may be a useful tool for non-invasive hemodynamic assessment of intermediate coronary lesions, while CT anatomical, plaque morphology, and peri-coronary adipose tissue assessment have no incremental or additional benefit. These findings might help to reduce pre-transcatheter aortic valve replacement invasive coronary angiogram., Key Points: • Interpreting the hemodynamic significance of intermediate coronary stenoses is challenging in pre-transcatheter aortic valve replacement CT. • CT-derived fractional flow reserve (CT-FFR) has a good discriminatory capacity in the identification of hemodynamically significant coronary lesions. • CT-derived anatomical, plaque morphology, and peri-coronary adipose tissue assessment did not improve the diagnostic capability of CT-FFR in the hemodynamic assessment of intermediate coronary stenoses., (© 2024. The Author(s).)

Background/Objectives: Previous trials reported comparable results with PASCAL and earlier MitraClip generations. Limited comparative data exist for more contemporary MitraClip generations, particularly the large MitraClip XT(R/W). We aimed to evaluate acute and 30-day outcomes in patients undergoing mitral valve transcatheter edge-to-edge repair (M-TEER) with one of the large devices, either PASCAL P10 or MitraClip XT(R/W) (3rd/4th generation). Methods: A total of 309 PASCAL-treated patients were matched by propensity score to 253 MitraClip-treated patients, resulting in 200 adequately balanced pairs. Procedural, clinical, and echocardiographic outcomes were collected for up to 30 days, including subgroup analysis for mitral regurgitation (MR) etiologies. Results : PASCAL and MitraClip patients were comparable regarding age (80 vs. 79 years), sex (female: 45.5% vs. 50.5%), and MR etiology (degenerative MR: n = 94, functional MR [FMR]: n = 96, mixed MR: n = 10 in each group). Technical success rates were comparable (96.5% vs. 96.0%; p > 0.999). At discharge, the mean gradient was higher (3.3 mmHg vs. 3.0 mmHg; p = 0.038), and the residual mitral valve orifice area was smaller in MitraClip patients (3.0 cm 2 vs. 2.3 cm 2 ; p < 0.001). At discharge, the reduction to MR ≤ 2+ was comparable (92.4% vs. 87.8%; p = 0.132). However, reduction to MR ≤ 1+ was more frequently observed in PASCAL patients (67.7% vs. 56.6%; p = 0.029), driven by the FMR subgroup (74.0% vs. 60.0%; p = 0.046). No difference was observed in 30-day mortality ( p = 0.204) or reduction in NYHA-FC to ≤II ( p > 0.999). Conclusions : Both M-TEER devices exhibited high and comparable rates of technical success and MR reduction to ≤2+. PASCAL may be advantageous in achieving MR reduction to ≤1+ in patients with FMR.

Background and Objectives: In light of limited intensive care capacities and a lack of accurate prognostic tools to advise caregivers and family members responsibly, this study aims to determine whether automated cerebral CT (CCT) analysis allows prognostication after out-of-hospital cardiac arrest., Methods: In this monocentric, retrospective cohort study, a supervised machine learning classifier based on an elastic net regularized logistic regression model for gray matter alterations on nonenhanced CCT obtained after cardiac arrest was trained using 10-fold cross-validation and tested on a hold-out sample (random split 75%/25%) for outcome prediction. Following the literature, a favorable outcome was defined as a cerebral performance category of 1-2 and a poor outcome of 3-5. The diagnostic accuracy was compared with established and guideline-recommended prognostic measures within the sample, that is, gray matter-white matter ratio (GWR), neuron-specific enolase (NSE), and neurofilament light chain (NfL) in serum., Results: Of 279 adult patients, 132 who underwent CCT within 14 days of cardiac arrest with good imaging quality were identified. Our approach discriminated between favorable and poor outcomes with an area under the curve (AUC) of 0.73 (95% CI 0.59-0.82). Thus, the prognostic power outperformed the GWR (AUC 0.66, 95% CI 0.56-0.76). The biomarkers NfL, measured at days 1 and 2, and NSE, measured at day 2, exceeded the reliability of the imaging markers derived from CT (AUC NfL day 1: 0.87, 95% CI 0.75-0.99; AUC NfL day 2: 0.90, 95% CI 0.79-1.00; AUC NSE day: 2 0.78, 95% CI 0.62-0.94)., Discussion: Our data show that machine learning-assisted gray matter analysis of CCT images offers prognostic information after out-of-hospital cardiac arrest. Thus, CCT gray matter analysis could become a reliable and time-independent addition to the standard workup with serum biomarkers sampled at predefined time points. Prospective studies are warranted to replicate these findings.

Background: Severe pure aortic regurgitation (AR) carries a high mortality and morbidity risk, and it is often undertreated because of the inherent surgical risk. Transcatheter heart valves (THVs) have been used off-label in this setting with overall suboptimal results. The dedicated "purpose-built" Jena Valve Trilogy (JVT, JenaValve Technology) showed an encouraging performance, although it has never been compared to other THVs., Objectives: The aim of our study was to assess the performance of the latest iteration of THVs used off-label in comparison to the purpose-built JVT in inoperable patients with severe AR., Methods: We performed a multicenter, retrospective registry with 18 participating centers worldwide collecting data on inoperable patients with severe AR of the native valve. A bicuspid aortic valve was the main exclusion criterion. The primary endpoints were technical and device success, 1-year all-cause mortality, and the composite of 1-year mortality and the heart failure rehospitalization rate., Results: Overall, 256 patients were enrolled. THVs used off-label were used in 168 cases (66%), whereas JVT was used in 88 (34%). JVT had higher technical (81% vs 98%; P < 0.001) and device success rates (73% vs 95%; P < 0.001), primarily driven by significantly lower incidences of THV embolization (15% vs 1.1%; P < 0.001), the need for a second valve (11% vs 1.1%; P = 0.004), and moderate residual AR (10% vs 1.1%; P = 0.007). The permanent pacemaker implantation rate was comparable and elevated for both groups (22% vs 24%; P = 0.70). Finally, no significant difference was observed at the 1-year follow-up in terms of mortality (HR: 0.99; P = 0.980) and the composite endpoint (HR: 1.5; P = 0.355)., Conclusions: The JVT platform has a better acute performance than other THVs when used off-label for inoperable patients with severe AR. A longer follow-up is conceivably needed to detect a possible impact on prognosis., Competing Interests: Funding Support and Author Disclosures This study has been performed at IRCCS Policlinico San Donato, a clinical research hospital partially funded by the Italian Ministry of Health. Dr Adam has received grants and personal fees from Medtronic; and has received personal fees from JenaValve, Edwards Lifesciences, and Boston Scientific. Dr Wienemann has received travel grants from JenaValve. Dr Panoulas has received consultancy fees for Medtronic; and has served as a proctor for Medtronic. Dr Taramasso has received consultancy fees from Abbott, Edwards Lifescience, Medtronic, Boston Scientific, Shenqi Medical, PiCardia, CoreMedic, CoreQuest, MEDIRA, Simulands, and VentriMend; and serves on the Advisory Boards for Abbott and HiD Imaging. Dr Baldus has received lecture fees from JenaValve; and has received lecture and speaker fees from Edwards Lifesciences. Dr Baumbach has received speaker/consultant fees from Medtronic, Biotronik, Meril, Sinomed, and Microport; and is a proctor for JenaValve. Dr Rudolph has received consultancy fees/speaker honoraria from Abbott, JenaValve, Edwards Lifesciences, and Medtronic. Dr Testa is a proctor/consultant for Abbott, Medtronic, Boston Scientific, and Meril; and has received speaker honoraria from Abbott, Medtronic, Boston Scientific, and Meril., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: A novel echocardiography-based definition of atrial functional tricuspid regurgitation (A-FTR) has shown superior outcomes in patients undergoing conservative treatment or tricuspid valve transcatheter edge-to-edge repair. Its prognostic significance for transcatheter tricuspid valve annuloplasty (TTVA) outcomes is unknown., Objectives: This study sought to investigate prognostic, clinical, and technical implications of A-FTR phenotype in patients undergoing TTVA., Methods: This multicenter study investigated clinical and echocardiographic outcomes up to 1 year in 165 consecutive patients who underwent TTVA for A-FTR (characterized by the absence of tricuspid valve tenting, midventricular right ventricular [RV] dilatation, and impaired left ventricular ejection fraction) and nonatrial functional tricuspid regurgitation (NA-FTR)., Results: A total of 62 A-FTR and 103 NA-FTR patients were identified, with the latter exhibiting more pronounced RV remodeling. Compared to baseline, the tricuspid regurgitation (TR) grade at discharge was significantly reduced (P < 0.001 for both subtypes), and TR ≤II was achieved more frequently in A-FTR (85.2% vs 60.8%; P = 0.001). Baseline TR grade and A-FTR phenotype were independently associated with TR ≤II at discharge and 30 days. In multivariate analyses, A-FTR phenotype was a strong predictor (OR: 5.8; 95% CI: 2.1-16.1; P < 0.001) of TR ≤II at 30 days. At 1 year, functional class had significantly improved compared to baseline (both P < 0.001). One-year mortality was lower in A-FTR (6.5% vs 23.8%; P = 0.011) without significant differences in heart failure hospitalizations (13.3% vs 22.7%; P = 0.188)., Conclusions: Direct TTVA effectively reduces TR in both A-FTR, which is a strong and independent predictor of achieving TR ≤II, and NA-FTR. Even though NA-FTR showed more RV remodeling at baseline, both phenotypes experienced similar symptomatic improvement, emphasizing the benefit of TTVA even in advanced disease stages. Additionally, phenotyping was of prognostic relevance in patients undergoing TTVA., Competing Interests: Funding Support and Author Disclosures Dr J. von Stein has received lecture fees from Edwards Lifesciences. Dr Iliadis has received travel support from Abbott and Edwards Lifesciences; and has received consultant honoraria from Abbott and Edwards Lifesciences. Dr Kalbacher has received personal fees from Edwards Lifesciences, Abbott, and Pi-Cardio Ltd; and has received research grants and honoraria for consultation from Edwards Lifesciences. Dr Rudolph has received research grants and honoraria for consultation from Edwards Lifesciences. Dr Baldus has received honoraria for consultation from Abbott and Edwards Lifesciences. Dr Pfister has received speaker fees from Edwards Lifesciences and Abbott. Dr Körber has received travel support from JenaValve; and has received lecture fees from Edwards Lifesciences and Abbott. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Aims: Paradoxical low-flow, low-gradient aortic stenosis (pLFLG AS) may represent a diagnostic challenge, and its pathophysiology is complex. While left ventricular (LV) systolic function is preserved, right ventricular dysfunction (RVD) and consecutive LV underfilling may contribute to low-flow and reduced stroke volume index, and to adverse outcomes following transcatheter aortic valve implantation (TAVI). The aim of this study was to evaluate the potential role of RVD in pLFLG AS, and to assess the impact of pre-procedural RVD on clinical outcomes after TAVI in patients with pLFLG AS., Methods and Results: Out of 2739 native AS patients, who received TAVI at the University of Cologne Heart Center between March 2013 and June 2021, 114 patients displayed pLFLG AS and were included in this study. Right ventricular (RV) function was assessed by transthoracic echocardiography, and a fractional area change (FAC) ≤35% and/or a tricuspid annular plane systolic excursion (TAPSE) <18 mm determined RVD. In addition, the TAPSE/systolic pulmonary artery pressure ratio (TAPSE/sPAP) was monitored as a measure of RV-pulmonary arterial (PA) coupling. An impaired FAC and TAPSE was present in 21.9% and 45.6% of patients, respectively, identifying RVD in 50.0%. RVD (p = 0.016), reduced FAC (p = 0.049), reduced TAPSE (p = 0.035) and impaired RV-PA coupling (TAPSE/sPAP ratio <0.31 mm/mmHg; p = 0.009) were associated with significantly higher all-cause mortality compared to patients with normal RV function. After adjustment for sex, age, body mass index, EuroSCORE II, previous myocardial infarction and mitral regurgitation, independent predictors for all-cause mortality were FAC, sPAP, TAPSE/sPAP ratio, right atrial area, RV diameter and tricuspid regurgitation., Conclusions: Adverse RV remodelling, RVD and impaired RV-PA coupling provide an explanation for low-flow and reduced stroke volume index in a subset of patients with pLFLG AS, and are associated with excess mortality after TAVI., (© 2024 The Author(s). European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Aims: In pulmonary arterial hypertension (PAH), upfront combination therapy with ERA and PDE5i is associated with a reduction in morbidity and mortality events and improves standard haemodynamics, but data remain limited. Aims of this study were (i) to capture detailed haemodynamic effects of rapid sequential dual combination therapy in patients with newly diagnosed PAH; (ii) to monitor the impact of treatment initiation on clinical variables and patients' risk status, and (iii) to compare the treatment effect in patients with 'classical PAH' and 'PAH with co-morbidities'., Methods: Fifty patients (median age 57 [42-71] years, 66% female) with newly diagnosed PAH (76% idiopathic) were treated with a PD5i/sGC-S or ERA, followed by addition of the respective other drug class within 4 weeks. All patients underwent repeat right heart catheterization (RHC) during early follow-up., Results: At early repeat RHC (7 ± 2 months), there were substantial reductions in mean pulmonary artery pressure (mPAP: 52.2 ± 13.5 to 39.0 ± 10.6 mmHg; -25.3%), and pulmonary vascular resistance (PVR: 12.1 ± 5.7 to 5.8 ± 3.1 WU; -52.1%), and an increase in cardiac index (2.1 ± 0.4 to 2.7 ± 0.7 mL/min/m 2 ; +32.2%) (all P < 0.05). Haemodynamic improvements correlated with improved clinical parameters including 6-min walking distance (336 ± 315 to 389 ± 120 m), NTproBNP levels (1.712 ± 2.024 to 506 ± 550 ng/L, both P < 0.05) and WHO-FC at 12 months, resulting in improved risk status, and were found in patients with few (n = 37) or multiple cardiovascular co-morbidities (BMI > 30 kg/m 2 , hypertension, diabetes, coronary artery disease [≥3]; n = 13), albeit baseline PVR in PAH patients with multiple co-morbidities was lower (9.3 ± 4.4 vs. 13.1 ± 5.9 WU) and PVR reduction less pronounced compared with those with few co-morbidities (-42.7% vs. -54.7%). However, comprehensive haemodynamic assessment considering further variables of prognostic relevance such as stroke volume index and pulmonary artery compliance showed similar improvements among the two groups (SVI: +50.0% vs. +49.2%; PA C : 91.7% vs. 100.0%). Finally, the 4-strata risk assessment approach was better able to capture treatment response as compared with other approaches, particularly in patients with co-morbidities., Conclusions: Rapid sequential combination therapy with PDE5i/sGC-S and ERA substantially ameliorates cardiopulmonary haemodynamics at early follow-up in patients without, and to a lesser extent, with cardiovascular co-morbidities. This occurs in line with improvements of clinical parameters and risk status., (© 2024 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background/Objectives: Chronic total occlusion (CTO) is a prevalent finding in patients with coronary artery disease and is associated with increased mortality. Prior reports on the efficacy of percutaneous coronary intervention (PCI) compared to optimal medical therapy (OMT) were controversial. Following the emergence of recently published new evidence, a meta-analysis is warranted. The current meta-analysis assessed the effects of PCI compared to OMT in the treatment of CTO. Methods: A structured literature search was performed. Randomized controlled trials (RCTs) and non-randomized controlled studies of interventions were eligible. The primary outcome was an accumulated composite of cardiac mortality, myocardial infarction and target vessel/lesion revascularization events. Results: Thirty-two studies reporting on 11260 patients were included. Of these, 5712 (50.7%) were assigned to the PCI and 5548 (49.3%) were allocated to the OMT group. The primary outcome occurred in 14.6% of the PCI and 20.1% of the OMT group (12 trials, OR 0.66, 95% CI 0.50 to 0.88, p = 0.005, I 2 = 67%). Subgrouping demonstrated a consistent reduction in the primary outcome for the PCI group in RCTs (six trials, OR 0.58, 95% CI 0.33 to 0.99, p = 0.05). The primary outcome reduction was irrespective of the study design, and it was replicable in sensitivity and subgroup analyses. Advantages in other outcomes were rather related to statistical pooling effects and dominated by observational data. Conclusions: CTO-PCI was associated with improved patient-oriented primary outcome compared to OMT in a study-level meta-analysis. This composite outcome effect was mainly driven by target vessel treatment, but a significant reduction in mortality and myocardial infarction was observed, irrespectively. These findings have hypothesis-generating implications. Future RCTs with adequate statistical power are eagerly awaited.

Objectives: The association of pulmonary hypertension (PH) with the outcome after mitral transcatheter edge-to-edge repair (M-TEER) focusing on the new ESC/ERS guidelines definition for PH., Background: PH is frequently found in patients with mitral regurgitation and is associated with lower survival rates. Recent studies were based on echocardiographic parameters, but results based on invasive haemodynamics differentiating distinct types of PH using the new definition for PH are missing., Methods: 449 consecutive M-TEER-treated patients from December 2009 to February 2015 were included in this retrospective analysis. All patients were stratified by the distinct types of PH (no PH, precapillary PH, isolated postcapillary PH, combined post-PH and precapillary PH) according to the definitions of the ESC/ERS guidelines for the diagnosis of PH from 2015 (meanPA cut-off <25 mm Hg, pulmonary capillary wedge pressure (PCWP) cut-off ≤15 mm Hg, diastolic pulmonary gradient cut-off ≥7 mm Hg or pulmonary vascular resistance (PVR) >3 WU) and 2022 (meanPA cut-off ≤20 mm Hg, PCWP cut-off ≤15 mm Hg, PVR cut-off ≥3 WU)., Results: Patients with any type of PH (2015: meanPA cut-off 25 mm Hg; 2022: meanPA cut-off >20 mm Hg) showed a higher risk of death after M-TEER compared with patients with no PH (2015: HR 1.61 (95% CI 1.25 to 2.07); p<0.001 and 2022: HR 2.09 (95% CI 1.54 to 2.83); p<0.001). Based on the new PH definition, each PH subgroup showed a lower survival after M-TEER compared with patients with no PH. Echocardiographic estimated systolic PAP showed a correlation with invasively measured mean pulmonary artery pressure (mPAP) (r=0.29, p<0.001) and systolic pulmonary arterial pressure (r=0.34,p<0.001). Cox-regression analysis showed higher invasive diastolic, systolic and mean pulmonary pressures were associated with higher all-cause mortality (p<0.001). In addition, invasive measured higher right atrial pressure, lower pulmonary arterial compliance, higher PVR and higher wedge pressure were identified as predictors of all-cause mortality after M-TEER., Conclusions: The new PH definition discriminates PH groups and mortality better than the old definition. The lower threshold of mPAP of 20mmHg improved prognostication in this cohort of patients., Competing Interests: Competing interests: TU, BF, K-HK and SR declare the full disclosure of any relationship with industry. IE received lecture honoraria and research grants by Abbott and lecture honoraria by Edwards. HA received travel support by Abbott. T. Schmidt, S. Willems, CF received lecture honoraria and travel support from Abbott Vascular and Edwards Lifesciences. RP received lecture honoraria from Abbott Vascular and Edwards and is a consultant for Edwards. SB received lecture honoraria and research grants from Edwards and Abbott., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Whether transcatheter mitral valve replacement (TMVR) devices perform similarly with respect to the underlying mitral regurgitation (MR) etiology remains unknown. The aim of the present analysis was to assess outcomes of TMVR according to the MR underlying etiology among the CHoice of OptImal transCatheter trEatment for Mitral Insufficiency (CHOICE-MI) registry., Methods: Of 746 patients, 229 patients (30.7%) underwent TMVR. The study population was subdivided according to primary, secondary, or mixed MR. Patients with mitral annular calcification were excluded. The primary study endpoint was a composite endpoint of all-cause mortality or hospitalization for heart failure at 1 year. Secondary study endpoints were all-cause and cardiovascular mortality at 1 year, New York Heart Association functional class, and residual MR, both at discharge and 1 year., Results: The predominant MR etiology was secondary MR (58.4%), followed by primary MR (28.7%) and mixed MR (12.9%). Technical success and procedural mortality were similar according to MR etiology. Discharge echocardiography revealed residual MR 2+ in 11.3%, 3.7%, and 5.3% of patients with primary, secondary, and mixed MR, respectively (P = .1). MR elimination was similar in all groups up to the 1-year follow-up. There was no difference in terms of primary combined outcome occurrence according to MR etiology. One-year all-cause mortality was reported in 28.8%, 24.2%, and 32.1% of patients with primary, secondary, and mixed MR, respectively (P = .07)., Conclusions: In our study we did not find differences in short-term and 1-year outcomes after TMVR according to MR etiology., (Copyright © 2024 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Introduction: Myocardial infarction (MI) is a significant contributor to morbidity and mortality worldwide. Many individuals who survive the acute event continue to experience heart failure (HF), with inflammatory and healing processes post-MI playing a pivotal role. Polymorphonuclear neutrophils (PMN) and monocytes infiltrate the infarcted area, where PMN release high amounts of the heme enzyme myeloperoxidase (MPO). MPO has numerous inflammatory properties and MPO plasma levels are correlated with prognosis and severity of MI. While studies have focused on MPO inhibition and controlling PMN infiltration into the infarcted tissue, less is known on MPO's role in monocyte function., Methods and Results: Here, we combined human data with mouse and cell studies to examine the role of MPO on monocyte activation and migration. We revealed a correlation between plasma MPO levels and monocyte activation in a patient study. Using a mouse model of MI, we demonstrated that MPO deficiency led to an increase in splenic monocytes and a decrease in cardiac monocytes compared to wildtype mice (WT). In vitro studies further showed that MPO induces monocyte migration, with upregulation of the chemokine receptor CCR2 and upregulation of inflammatory pathways identified as underlying mechanisms., Conclusion: Taken together, we identify MPO as a pro-inflammatory mediator of splenic monocyte recruitment and activation post-MI and provide mechanistic insight for novel therapeutic strategies after ischemic injury., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Peters, Matheis, Erdmann, Nemade, Muders, Toubartz, Torun, Mehrkens, Geißen, Nettersheim, Picard, Guthoff, Hof, Arkenberg, Arand, Klinke, Rudolph, Hansen, Bachurski, Adam, Hoyer, Winkels, Baldus and Mollenhauer.)

Background: Surgery remains the only recommended intervention for patients with native aortic regurgitation. A transcatheter therapy to treat patients at high risk for mortality and complications with surgical aortic valve replacement represents an unmet need. Commercial transcatheter heart valves in pure aortic regurgitation are hampered by unacceptable rates of embolisation and paravalvular regurgitation. The Trilogy transcatheter heart valve (JenaValve Technology, Irvine, CA, USA) provides a treatment option for these patients. We report outcomes with transfemoral transcatheter aortic valve implantation (TAVI) in patients with pure aortic regurgitation using this dedicated transcatheter heart valve., Methods: The ALIGN-AR trial is a prospective, multicentre, single-arm study. We recruited symptomatic patients (aged ≥18 years) with moderate-to-severe or severe aortic regurgitation at high risk for mortality and complications after surgical aortic valve replacement at 20 US sites for treatment with the Trilogy transcatheter heart valve. The 30-day composite primary safety endpoint was compared for non-inferiority with a prespecified performance goal of 40·5%. The primary efficacy endpoint was 1-year all-cause mortality compared for non-inferiority with a performance goal of 25%. This trial is registered with ClinicalTrials.gov, NCT04415047, and is ongoing., Findings: Between June 8, 2018, and Aug 29, 2022, we screened 346 patients. We excluded 166 (48%) patients and enrolled 180 (52%) patients with symptomatic aortic regurgitation deemed high risk by the heart team and independent screening committee assessments. The mean age of the study population was 75·5 years (SD 10·8), and 85 (47%) were female, 95 (53%) were male, and 131 (73%) were White. Technical success was achieved in 171 (95%) patients. At 30 days, four (2%) deaths, two (1%) disabling strokes, and two (1%) non-disabling strokes occurred. Using standard Valve Academic Research Consortium-2 definitions, the primary safety endpoint was achieved, with events occurring in 48 (27% [97·5% CI 19·2-34·0]) patients (p non-inferiority <0·0001), with new pacemaker implantation in 36 (24%) patients. The primary efficacy endpoint was achieved, with mortality in 14 (7·8% [3·3-12·3]) patients at 1 year (p non-inferiority <0·0001)., Interpretation: This study shows the safety and effectiveness of treating native aortic regurgitation using a dedicated transcatheter heart valve to treat patients with symptomatic moderate-to-severe or severe aortic regurgitation who are at high risk for mortality or complications after surgical aortic valve replacement. The observed short-term clinical and haemodynamic outcomes are promising as are signs of left ventricular remodelling, but long-term follow-up is necessary., Funding: JenaValve Technology., Competing Interests: Declaration of interests TPV reports institutional funding to Columbia University Irving Medical Center from JenaValve Technology, Abbott Vascular, Boston Scientific, Edwards Lifesciences, and Medtronic; and he personally received consulting fees from 4C Medical and Philips. OKK reports that he is part of a core laboratory contracting with JenaValve Technology but he has not received any direct compensation; he further reports consulting fees from Edwards Lifesciences, VDyne, Siemens, Philips, Laralab, and Restore Medical. NH reports that she is part of a core laboratory contracting with JenaValve Technology but she has not received any direct compensation. JMM reports consulting fees and honoraria from Edwards Lifesciences, Medtronic, Abbott, Shockwave, and Equity in Excision Medical, and Conkay Medical. IG reports consulting fees from Edwards Lifesciences, Medtronic, Boston Scientific, Abbott SJM, and Atricure. SKK reports consultant fees (honoraria) from Admedus, Meril Lifesciences, JenaValve Technology, and Abbott Vascular; scientific advisory board participation (equity) with Dura Biotech, MicroInterventional Devices, Thubrikar Aortic Valve, Supira, and Admedus; and institutional funding to Columbia University and the Cardiovascular Research Foundation from Edwards Lifesciences, Medtronic, Abbott Vascular, Boston Scientific, and JenaValve Technology. NA reports medical advisory board fees and consultant and proctor fees from Nininger Medical, Edwards Lifesciences, V-wave, JenaValve Technology, Abbott, Vdyne, and Boston Scientific, and participation in industry-sponsored trials and research funding from Edwards Lifesciences, JenaValve Technology, Boston Scientific, V-wave, AccuCinch, Highlife, Tendyne, and preCardia. DSP is the Chief Medical officer of JenaValve Technology and a consultant for Abiomed, Abbott Vascular, Magenta, NuPulseCV, and Terumo. MBL reports institutional clinical research grants from Abbott, Boston Scientific, Edwards Lifesciences, Medtronic, and JenaValve Technology. HG reports consulting fees from Medtronic and Boston Scientific. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Mitral transcatheter edge-to-edge repair (M-TEER) is a guideline-recommended treatment option for patients with severe symptomatic mitral regurgitation (MR). Outcomes with the PASCAL system in a post-market setting have not been established., Objectives: The authors report 30-day and 1-year outcomes from the MiCLASP (Transcatheter Repair of Mitral Regurgitation with Edwards PASCAL Transcatheter Valve Repair System) European post-market clinical follow-up study., Methods: Patients with symptomatic, clinically significant MR were prospectively enrolled. The primary safety endpoint was clinical events committee-adjudicated 30-day composite major adverse event rate and the primary effectiveness endpoint was echocardiographic core laboratory-assessed MR severity at discharge compared with baseline. Clinical, echocardiographic, functional, and quality-of-life outcomes were assessed at 1 year., Results: A total of 544 patients were enrolled (59% functional MR, 30% degenerative MR). The 30-day composite major adverse event rate was 6.8%. MR reduction was significant from baseline to discharge and sustained at 1 year with 98% of patients achieving MR ≤2+ and 82.6% MR ≤1+ (all P < 0.001 vs baseline). One-year Kaplan-Meier estimate for survival was 87.3%, and freedom from heart failure hospitalization was 84.3%. Significant functional and quality-of-life improvements were observed at 1 year, including 71.6% in NYHA functional class I/II, 14.4-point increase in Kansas City Cardiomyopathy Questionnaire score, and 24.2-m improvement in 6-minute walk distance (all P < 0.001 vs baseline)., Conclusions: One-year outcomes of this large cohort from the MiCLASP study demonstrate continued safety and effectiveness of M-TEER with the PASCAL system in a post-market setting. Results demonstrate high survival and freedom from heart failure hospitalization, significant and sustained MR reduction, and improvements in symptoms, functional capacity, and quality of life., Competing Interests: Funding Support and Author Disclosures This work was supported by Edwards Lifesciences. Prof Lurz has received institutional fees and research grants from Abbott Vascular, Edwards Lifesciences, Medtronic, ReCor, and Occlutech. Dr Schmitz has received speaker fees and proctor honorarium from Edwards Lifesciences and Abbott. Dr Geisler has received personal fees (lecture honoraria) and institutional research grants from Edwards Lifesciences. Dr Hausleiter is a consultant and receives speaker fees and institutional research support from Edwards Lifesciences. Prof Eitel has received research grants from Abbott Vascular and speaker fees from Abbott, Edwards Lifesciences, and Boston Scientific. Dr Rudolph has received research grants from Edwards Lifesciences, Abbott, and Boston Scientific. Dr Lubos has received grants from Abbott and personal fees from Abbott, Abiomed, AstraZeneca, Bayer, Edwards Lifesciences, New Valve Technology, and Novartis. Dr von Bardeleben is a principal investigator for Abbott, DZHK, Edwards Lifesciences, JensCare, Medtronic, NeoChord, and the University of Göttingen IIT; and serves as an advisor, proctor, or speaker for Abbott, Edwards Lifesciences, JenaValve, JensCare, Medtronic, NeoChord, Philips, and Siemens. Dr Berti has received honoraria from and is a consultant for Proctor & Gamble, Abbott, and Boston Scientific. Dr De Marco has received honoraria and consultation fees from Edwards Lifesciences. Dr Linke has received grants from Novartis and Edwards Lifesciences; personal fees from Abbott, Abiomed, AstraZeneca, Bayer, Boehringer Ingelheim, Boston Scientific, Edwards Lifesciences, Medtronic, Novartis, Sanofi Genzyme, and Pfizer; and other fees from Picardia, Filterlex, and Transverse Medical outside the submitted work. Dr Hengstenberg has received institutional research grants from Edwards Lifesciences, Boston Scientific, Abbott, and Medtronic; and serves as a proctor for Edwards Lifesciences and Boston Scientific. Dr Baldus has received a research grant from Abbott; and lecture fees from Abbott and Edwards Lifesciences. Dr Spargias has received honoraria or consultation fees from Edwards Lifesciences, Abbott Vascular, and Medtronic. Dr Denti is a consultant for InnovHeart, Approxima, Picardia, and HRV; and receives speaker fees from Edwards Lifesciences and Abbott. Prof Nickenig has received research funding from the Deutsche Forschungsgemeinschaft, the German Federal Ministry of Education and Research, the EU, Abbott, AGA Medical, AstraZeneca, Bayer, Berlin Chemie, Biosensus, Biotronic, Bristol Myers Squibb, Boehringer Ingelheim, Daiichi-Sankyo, Edwards Lifesciences, Medtronic, Novartis, Pfizer, Sanofi, and St. Jude Medical; and has received honoraria for lectures or advisory boards from Abbott, AGA Medical, AstraZeneca, Bayer, Berlin, Cardiovalve, Berlin Chemie, Biosensus, Biotronic, Bristol Myers Squibb, Boehringer Ingelheim, Daiichi-Sankyo, Edwards Lifesciences, Medtronic, Novartis, Pfizer, Sanofi, and St. Jude Medical. Prof Möllmann has receives speaker/proctor fees from Abbott, Boston Scientific, Edwards Lifesciences, Medtronic, and SMT. Prof Rottbauer is a consultant for and receives speaker honoraria from Edwards Lifesciences. Dr Praz received travel expenses from Edwards Lifesciences, Abbott Vascular, Polares Medical, Medira, and Siemens Healthineers. Dr Butter has received lecture fees from Edwards Lifesciences and Abbott; and educational grants from Boston Scientific. Dr Van Mieghem has received research grants from Abbott Vascular, Boston Scientific, Medtronic, Edwards Lifesciences, Daiichi-Sankyo, AstraZeneca, and Teleflex; and scientific advisory fees from Anteris, JenaValve, Abbott Vascular, Boston Scientific, Medtronic, Amgen, Daiichi-Sankyo, Siemens, Pie Medical, and Teleflex. Dr Sherif is a consultant for and receives speaker honoraria from Edwards Lifesciences. Dr Swaans is a proctor/lecturer for Abbott Vascular, Boston Scientific, Bioventrix, Cardiac Dimensions, Edwards Lifesciences, GE Healthcare, Medtronic, and Philips Healthcare. Dr Witkowski is an advisory board member and has received honoraria from Abbott and Edwards Lifesciences. Dr Buch participates in the Abbott structural heart advisory group; and has received honoraria from Abbott. Prof Seidler has received honoraria for lectures, advisory boards, or travel grants from Abbott Vascular, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Corvia, Cytokinetics, Edwards Lifesciences, Medtronic, Myocardia, Novartis, Pfizer, and Teleflex. Dr Eißmann has received honoraria or consultation fees from Edwards Lifesciences and Abbott Vascular. Dr Marcoff serves as a member of the echocardiography core laboratory for Edwards Lifesciences and Abbott for which he receives no direct compensation. Dr Koulogiannis is a consultant and advisory board member for Edwards Lifesciences; and a speaker for Abbott. Dr Rassaf has received research funding from the Deutsche Forschungsgemeinschaft and Abbott; and receives honoraria for lectures or advisory boards from AstraZeneca, Bayer, Berlin Chemie, Bristol Myers Squibb, Boehringer Ingelheim, Daiichi-Sankyo, Medtronic, Novartis, and Pfizer. Dr Luedike received research grants and honoraria for consulting and lectures from Edwards Lifesciences, Novartis, and Pfizer. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Aims: While invasively determined congestion holds mechanistic and prognostic significance in acute heart failure (HF), its role in patients with tricuspid regurgitation (TR)-related right- heart failure (HF) undergoing transcatheter tricuspid valve intervention (TTVI) is less well established. A comprehensive understanding of congestion patterns might aid in procedural planning, risk stratification, and the identification of patients who may benefit from adjunctive therapies before undergoing TTVI. The aim of this study was to investigate the role of congestion patterns in patients with severe TR and its implications for TTVI., Methods and Results: Within a multicentre, international TTVI registry, 813 patients underwent right heart catheterization (RHC) prior to TTVI and were followed up to 24 months. The median age was 80 (interquartile range 76-83) years and 54% were women. Both mean right atrial pressure (RAP) and pulmonary capillary wedge pressure (PCWP) were associated with 2-year mortality on Cox regression analyses with Youden index-derived cut-offs of 17 mmHg and 19 mmHg, respectively (p < 0.01 for all). However, RAP emerged as an independent predictor of outcomes following multivariable adjustments. Pre-interventionally, 42% of patients were classified as euvolaemic (RAP <17 mmHg, PCWP <19 mmHg), 23% as having left-sided congestion (RAP <17 mmHg, PCWP ≥19 mmHg), 8% as right-sided congestion (RAP ≥17 mmHg, PCWP <19 mmHg), and 27% as bilateral congestion (RAP ≥17 mmHg, PCWP ≥19 mmHg). Patients with right-sided or bilateral congestion had the lowest procedural success rates and shortest survival times. Congestion patterns allowed for discerning specific patient's physiology and specifying prognostic implications of right ventricular to pulmonary artery coupling surrogates., Conclusion: In this large cohort of invasively characterized patients undergoing TTVI, congestion patterns involving right-sided congestion were associated with low procedural success and higher mortality rates after TTVI. Whether pre-interventional reduction of right-sided congestion can improve outcomes after TTVI should be established in dedicated studies., (© 2024 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Purpose: The introduction of HER2-targeting antibody drug conjugates (ADCs) offers new treatment options for female breast cancer patients (FBC) expressing low levels of HER2 (HER2 low). No evidence was found that HER2 low describes a new FBC subtype. There is a lack of studies determining the impact of HER2 low in male breast cancer (MBC). In this study, we evaluate the prevalence of HER2 low in primary MBC and correlate the results with patient characteristics., Patients and Methods: In this study, histological specimens were obtained from 120 male patients diagnosed and treated for primary invasive breast cancer from 1995 to 2022 at Breast Cancer Units in Bergisch Gladbach, Chemnitz, and Zwickau, Germany. HER2 immunostaining and in situ hybridization were performed by central pathology and evaluated based on the ASCO/CAP guidelines. The correlation of expression of HER2 low with tumor biological characteristics and patient outcomes was investigated., Results: Out of all cases, four patients (3.3%) showed HER2 positivity (3+), 39 (32.5%) patients were classified as HER2 low, 7 (5.8%) were HER2 2+ (no amplification), 32 (26.7%) were HER2 1+, and 77 (64.2%) were classified as HER2 zero. Out of 77 HER2 zero cases, 47 tumors (61.0%) showed incomplete staining, with <10% of tumor cells classified as HER2 ultralow. No statistical correlation between HER2 low and tumor biological characteristics and patients' survival was found., Conclusion: Our findings show a notable, albeit lower, prevalence of HER2 low expression in primary MBC. However, tumors expressing HER2 low do not show specific tumor biological features to define a new breast cancer subtype in MBC. Our results suggest that a significant number of MBC patients could benefit from ADCs, as shown in FBC. Further studies are required to better understand HER2 low breast cancer, both generally and in MBC., Competing Interests: The authors report no conflicts of interest in this work., (© 2024 Nobbe et al.)

Aims: Right ventricular to pulmonary artery (RV-PA) coupling has been established as a prognostic marker in patients with severe tricuspid regurgitation (TR) undergoing transcatheter tricuspid valve interventions (TTVI). RV-PA coupling assesses right ventricular systolic function related to pulmonary artery pressure levels, which are ideally measured by right heart catheterization. This study aimed to improve the RV-PA coupling concept by relating tricuspid annular plane systolic excursion (TAPSE) to mean pulmonary artery pressure (mPAP) levels. Moreover, instead of right heart catheterization, this study sought to employ an extreme gradient boosting (XGB) algorithm to predict mPAP levels based on standard echocardiographic parameters., Methods and Results: This multicentre study included 737 patients undergoing TTVI for severe TR; among them, 55 patients from one institution served for external validation. Complete echocardiography and right heart catheterization data were available from all patients. The XGB algorithm trained on 10 echocardiographic parameters could reliably predict mPAP levels as evaluated on right heart catheterization data from external validation (Pearson correlation coefficient R: 0.68; P value: 1.3 × 10-8). Moreover, predicted mPAP (mPAPpredicted) levels were superior to echocardiographic systolic pulmonary artery pressure (sPAPechocardiography) levels in predicting 2-year mortality after TTVI [area under the curve (AUC): 0.607 vs. 0.520; P value: 1.9 × 10-6]. Furthermore, TAPSE/mPAPpredicted was superior to TAPSE/sPAPechocardiography in predicting 2-year mortality after TTVI (AUC: 0.633 vs. 0.586; P value: 0.008). Finally, patients with preserved RV-PA coupling (defined as TAPSE/mPAPpredicted > 0.617 mm/mmHg) showed significantly higher 2-year survival rates after TTVI than patients with reduced RV-PA coupling (81.5% vs. 58.8%, P < 0.001). Moreover, independent association between TAPSE/mPAPpredicted levels and 2-year mortality after TTVI was confirmed by multivariate regression analysis (P value: 6.3 × 10-4)., Conclusion: Artificial intelligence-enabled RV-PA coupling assessment can refine risk stratification prior to TTVI without necessitating invasive right heart catheterization. A comparison with conservatively treated patients is mandatory to quantify the benefit of TTVI in accordance with RV-PA coupling., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Transcatheter aortic valve replacement (TAVR) has become an established alternative to surgical aortic valve replacement (AVR) for patients with moderate-to-high perioperative risk. Periprocedural TAVR complications decrease with growing expertise of implanters. Nevertheless, TAVR can still be accompanied by life-threatening adverse events such as intraprocedural cardiopulmonary resuscitation (CPR). This study analyzed the role of a reduced left-ventricular ejection fraction (LVEF) in intraprocedural complications during TAVR. Perioperative and postoperative outcomes from patients undergoing TAVR in a high-volume center (600 cases per year) were analyzed retrospectively with regard to their left-ventricular ejection fraction. Patients with a reduced left-ventricular ejection fraction (EF ≤ 40%) faced a significantly higher risk of perioperative adverse events. Within this cohort, patients were significantly more often in need of mechanical ventilation (35% vs. 19%). These patients also underwent CPR (17% vs. 5.8%), defibrillation due to ventricular fibrillation (13% vs. 5.4%), and heart-lung circulatory support (6.1% vs. 2.5%) more often. However, these intraprocedural adverse events showed no significant impact on postoperative outcomes regarding in-hospital mortality, stroke, or in-hospital stay. A reduced preprocedural LVEF is a risk factor for intraprocedural adverse events. With respect to this finding, the identified patient cohort should be treated with more caution to prevent intraprocedural incidents.

Background: Early studies of the Tendyne transcatheter mitral valve replacement (TMVR) showed promising results in a small selective cohort., Objectives: The authors present 1-year data from the currently largest commercial, real-world cohort originating from the investigator-initiated TENDER (Tendyne European Experience) registry., Methods: All patients from the TENDER registry eligible for 1-year follow-up were included. The primary safety endpoint was 1-year cardiovascular mortality. Primary performance endpoint was reduction of mitral regurgitation (MR) up to 1 year., Results: Among 195 eligible patients undergoing TMVR (median age 77 years [Q1-Q3: 71-81 years], 60% men, median Society of Thoracic Surgeons Predicted Risk of Mortality 5.6% [Q1-Q3: 3.6%-8.9%], 81% in NYHA functional class III or IV, 94% with MR 3+/4+), 31% had "real-world" indications for TMVR (severe mitral annular calcification, prior mitral valve treatment, or others) outside of the instructions for use. The technical success rate was 95%. The cardiovascular mortality rate was 7% at 30 day and 17% at 1 year (all-cause mortality rates were 9% and 29%, respectively). Reintervention or surgery following discharge was 4%, while rates of heart failure hospitalization reduced from 68% in the preceding year to 25% during 1-year follow-up. Durable MR reduction to ≤1+ was achieved in 98% of patients, and at 1 year, 83% were in NYHA functional class I or II. There was no difference in survival and major adverse events between on-label use and "real-world" indications up to 1 year., Conclusions: This large, real-world, observational registry reports high technical success, durable and complete MR elimination, significant clinical benefits, and a 1-year cardiovascular mortality rate of 17% after Tendyne TMVR. Outcomes were comparable between on-label use and "real-world" indications, offering a safe and efficacious treatment option for patients without alternative treatments. (Tendyne European Experience Registry [TENDER]; NCT04898335)., Competing Interests: Funding Support and Author Disclosures The TENDER study was carried out without financial support from industry. It was initiated as an academic investigator trial by LMU University Hospital and Universitätsmedizin Mainz. Dr Baldus has received research grants and honoraria from Abbott and Edwards Lifesciences. Dr Rudolph has received speaker honoraria from Abbott. Dr Andreas has received proctoring, consulting, and speaker fees from Edwards Lifesciences, Abbott, Medtronic, Boston, Zoll, and AbbVie; and institutional research grants from Edwards Lifesciences, Abbott, Medtronic, and LSI. Dr Duncan has received consulting fees and honoraria from Abbott, Edwards Lifesciences, Medtronic, NeoChord. Dr Nombela serves as a physician proctor for and has received advisory fees from Abbott Cardiovascular, Edwards Lifesciences, and Products + Features. Dr Ruge serves as a physician proctor for and has received advisory fees from Abbott Medical. Dr Conradi serves as an advisory board member for Abbott, Medtronic, and JenaValve; and is a consultant for Edwards Lifesciences, Boston Scientific, MicroPort, Pi-Cardia. Dr Dumonteil has received consulting and proctoring fees from Abbott, Boston Scientific, Edwards Lifesciences, and Medtronic. Dr Barth has received speaker and advisory fees from Abbott Cardiovascular and Edwards Lifesciences. Dr Adamo has received speaker honoraria from Abbott, Medtronic, and Edwards Lifesciences. Dr Maisano has received grant and/or research institutional support from Abbott, Medtronic, Edwards Lifesciences, Biotronik, Boston Scientific, New Valve Technology, Terumo, and Venus; has received consulting fees and personal and institutional honoraria from Abbott, Medtronic, Edwards Lifesciences, Xeltis, Cardiovalve, Occlufit, Simulands, MTEX Cardio, Venus, and Squadra; has received royalty income from and holds intellectual property rights with Edwards Lifesciences; is a shareholder (including share options) in CardioGard, Cardiovalve, Magenta, SwissVortex, Transseptal Solutions, 4Tech, and Perifect. Dr Lurz has received honoraria from ReCor Medical and Innoventric; and has received institutional grants from Edwards Lifesciences and ReCor. Dr Hausleiter has received speaker fees, research support, and advisory fees from Edwards Lifesciences. Dr von Bardeleben has received speaker or advisory fees from Abbott Cardiovascular, Edwards Lifesciences, Medtronic, NeoChord, Philips, and Siemens; and has conducted unpaid trial activity for Abbott Cardiovascular, Edwards Lifesciences, Jenscare Scientific, Medtronic, and NeoChord. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Severe tricuspid regurgitation (TR) is associated with chronic volume overload and right ventricular remodeling (RVR). Transcatheter tricuspid valve repair (TTVr) reduces TR and can improve quality of life (QoL), but the role of preprocedural RVR on TTVr outcomes remains unclear., Aims: To investigate the role of RVR on outcomes after TTVr for severe TR., Methods: Consecutive patients undergoing TTVr (61% edge-to-edge vs. 39% direct annuloplasty) for severe TR were retrospectively compared by preexisting RVR which was defined as dilation of RV mid-level diameter (> 35 mm) according to guidelines. QoL was evaluated using NYHA class, Minnesota Living with Heart Failure Questionnaire (MLHFQ), 36-Item Short Form Health Survey (SF-36), and 6-min walking distance (6MWD) 1-month after TTVr. Mid-term mortality and heart failure (HF) hospitalization were assessed through 1 year., Results: RVR was present in 137 of 223 patients (61%). Symptoms and QoL improved equally in both groups: ≥ 1 NYHA class (57% vs. 65% of patients with vs. without RVR, respectively), 6MWD (36% vs. 34%), MLHFQ (81% vs. 69%), and SF-36 (68% vs. 65%) improvement. One-year mortality and HF hospitalization were significantly higher in patients with RVR (24% and 30%, respectively) than in patients without (8% and 13%, both p < 0.05). In multivariable analysis, RVR was independently associated with mortality (HR 2.3, 95%CI (1.0-5.0), p = 0.04) and the combined endpoint of mortality or rehospitalization (HR 2.0, 95%CI (1.1-3.8), p = 0.03)., Conclusions: TTVr was associated with significant QoL improvement after 1 month, irrespective of RVR. Despite increased mortality and rehospitalization for heart failure, TTVr in the presence of RVR still provides substantial symptomatic benefit for patients with severe TR., (© 2024. The Author(s).)

Background: Bleeding is the most common complication after percutaneous leaflet-based tricuspid valve repair and associated with acute kidney injury (AKI) and adverse outcome. TTVA with the Cardioband system is a technically more complex procedure; however, frequency and prognostic impact of postinterventional bleeding and renal complications have not been thoroughly examined., Aims: This study was performed to determine the incidence and clinical impact of bleeding complications (MVARC criteria) and acute kidney injury (KDIGO criteria) following transcatheter tricuspid valve annuloplasty (TTVA)., Methods: In a bi-center retrospective analysis of patients undergoing TTVA between 2018 and 2022, we examined frequency, predictors, and clinical impact of bleeding and renal failure., Results: In 145 consecutive patients, the incidence of any MVARC bleeding was 20.7% (n = 30), whereas major MVARC bleeding occurred in 6.9% (n = 10). The incidence of AKI was 18.6% (n = 27). Risk factors for bleeding events included low baseline hemoglobin and elevated baseline creatinine levels. Risk factors for AKI included diabetes mellitus, arterial hypertension, high body mass index, and elevated baseline creatinine levels. Neither procedure duration nor amount of contrast media was associated with AKI or bleeding. Both bleeding and AKI led to a longer hospital stay. At 3 months, 10.0% (n = 3) of patients with bleeding and 7.8% (n = 9) of patients without bleeding complications died (p = 0.70). Additionally, mortality rate was 7.4% (n = 2) in patients with AKI compared to 8.5% (n = 10) without AKI (p = 0.83)., Conclusion: While about a fifth of patients undergoing TTVA suffered from postinterventional AKI or bleeding, none of these complications was associated with higher mortality at short-term follow-up. One important risk factor for both complications was chronic renal dysfunction, indicating a high-risk patient population. The most frequent bleeding localizations were the femoral access site, pericardial hemorrhage, and the esophagus, which need explicit attention in periprocedural management., (© 2024. The Author(s).)

Background: Frailty is common in elderly and multimorbid patients and associated with increased vulnerability to stressors., Methods: In a single centre study frailty according to Fried criteria was assessed in consecutive patients before transcatheter mitral and tricuspid valve repair. Postprocedural infections, blood transfusion and bleeding and renal failure were retrospectively assessed from records. Median follow-up time for survival was 560 days (IQR: 363 to 730 days)., Results: 90% of 626 patients underwent mitral valve repair, 5% tricuspid valve repair, and 5% simultaneous mitral and tricuspid valve repair. 47% were classified as frail. Frailty was associated with a significantly increased frequency of bleeding (16 vs 10%; p = 0.016), blood transfusions (9 vs 3%; p =  < 0.001) and infections (18 vs 10%; p = 0.006), but not with acute kidney injury (20 vs 20%; p = 1.00). Bleeding and infections were associated with longer hospital stays, with a more pronounced effect in frail patients (interaction test p < 0.05, additional 3.2 and 4.1 days in frail patients, respectively). Adjustment for the occurrence of complications did not attenuate the increased risk of mortality associated with frailty (HR 2.24 [95% CI 1.62-3.10]; p < 0.001)., Conclusions: Bleeding complications and infections were more frequent in frail patients undergoing transcatheter mitral and tricuspid valve repair and partly explained the longer hospital stay. Albeit some of the complications were associated with higher long-term mortality, this did not explain the strong association between frailty and mortality. Further research is warranted to explore interventions targeting periprocedural complications to improve outcomes in this vulnerable population., (© 2024. The Author(s).)

Background: Aortic stenosis has pathophysiological similarities with atherosclerosis, including the deposition of cholesterol-containing lipoproteins. The resulting cholesterol crystals activate the NLRP3 (NOD-like receptor protein 3) inflammasome, leading to inflammation and cardiovascular diseases. We aimed to investigate the cholesterol crystal dissolution rate (CCDR) of serum in patients with aortic stenosis and to assess the prognostic value of this biomarker., Methods and Results: The study included 348 patients with aortic stenosis undergoing transcatheter aortic valve replacement. The CCDR was measured using flow cytometry to enumerate cholesterol crystals that were added to a serum solution, at baseline and after 2 hours of incubation. Based on the median CCDR, the cohort was stratified into high and low cholesterol crystal dissolvers. The incidence of the primary end point, a composite of 1-year all-cause mortality and major vascular complication, was significantly lower in the high CCDR group (7.3 per 100 person-years) compared with the low CCDR group (17.0 per 100 person-years, P =0.01). This was mainly driven by a lower 1-year mortality rate in patients with a high CCDR (7.3 versus 15.1 per 100 person-years, P =0.04). Unplanned endovascular interventions were significantly less frequent in high cholesterol crystal dissolvers (12.8 versus 22.6 per 100 person-years, P =0.04). Although low-density lipoprotein cholesterol levels were comparable in both groups (101.8±37.3 mg/dL versus 97.9±37.6 mg/dL, P =0.35), only patients with a low CCDR showed a benefit from statin treatment. In multivariate analysis, low CCDR (hazard ratio, 2.21 [95% CI, 0.99-4.92], P =0.04) was significantly associated with 1-year mortality., Conclusions: The CCDR is a novel biomarker associated with outcome in patients with aortic stenosis undergoing transcatheter aortic valve replacement. It may provide new insights into patients' anti-inflammatory capacity and additional prognostic information beyond classic risk assessment.

Myeloperoxidase (MPO) is an enzyme that functions in host defense. MPO is released into the vascular lumen by neutrophils during inflammation and may adhere and subsequently penetrate endothelial cells (ECs) coating vascular walls. We show that MPO enters the nucleus of ECs and binds chromatin independently of its enzymatic activity. MPO drives chromatin decondensation at its binding sites and enhances condensation at neighboring regions. It binds loci relevant for endothelial-to-mesenchymal transition (EndMT) and affects the migratory potential of ECs. Finally, MPO interacts with the RNA-binding factor ILF3 thereby affecting its relative abundance between cytoplasm and nucleus. This interaction leads to change in stability of ILF3-bound transcripts. MPO-knockout mice exhibit reduced number of ECs at scar sites following myocardial infarction, indicating reduced neovascularization. In summary, we describe a non-enzymatic role for MPO in coordinating EndMT and controlling the fate of endothelial cells through direct chromatin binding and association with co-factors., Competing Interests: The authors declare no competing interests., (© 2024 The Author(s).)

Background: Transcatheter repair emerges as a treatment option in patients with tricuspid regurgitation (TR) and high surgical risk., Aims: This study aimed to compare leaflet-based and annuloplasty-based transcatheter repair in patients with TR., Methods: In a retrospective analysis consecutive patients undergoing either transcatheter edge-to-edge repair (TEER) or direct annuloplasty (AP) for relevant TR at 2 centers were compared with respect to baseline characteristics, procedural efficacy and safety (death, myocardial infarction, procedure or device-related cardiothoracic surgery, or stroke at 30 days)., Results: 161 patients (57% female, median age 79 [75-82] years) with comparable clinical baseline characteristics in the TEER (n = 87) and AP (n = 74) group were examined. Baseline TR grade was significantly less severe in the TEER compared to the AP group (torrential 9.2 vs. 31.1%, p = 0.001). Technical success and improvement of TR grades were not significantly different across groups. In analysis matched for baseline TR severity, reduction of TR grade to less than moderate was significantly more common in the AP group (47.8 vs. 26.1%, p = 0.031). Major or more severe bleeding occurred in 9.2% of TEER and 20.3% of AP patients (p = 0.049) without any fatal bleedings. Major adverse events (MAE) were similar across groups with four patients (4.7%) in the TEER group and five patients (6.9%) in the AP group (p = 0.733) and 6-month survival did not differ significantly., Conclusions: Differences observed between patients treated with TEER and AP provide first evidence for tailoring distinct transcatheter treatment techniques to individual patient characteristics., (© 2023. The Author(s).)

Background: Many patients in need for transcatheter aortic valve implantation (TAVI) present with an aortic annulus size larger than recommended by the manufacturer's instructions for use (IFU)., Aims: To investigate procedural and short-term safety and efficacy of TAVI in patients with extra-large annuli (ELA)., Methods: 30-day clinical outcome and valve performance as defined by VARC 3 of 144 patients with an aortic annulus size exceeding the permitted range were compared to a propensity-score matched control cohort of patients with an aortic annulus size consistent with the IFU., Results: Area and perimeter was 730.4 ± 53.9 mm 2 and 96.7 ± 6.5 mm in the ELA group. Technical (96.5% vs. 94.4%) and device success (82.3% vs. 84.5%) were comparable in patients with ELA (annulus area 730.4 ± 53.9 mm 2 ) and matched controls (annulus area 586.0 ± 48.2 mm 2 ). There was no significant difference in 30-day mortality rate, major intraprocedural complications, type 3 or 4 bleedings, major vascular complications, or stroke. Moderate paravalvular leakage (PVL) occurred more frequent in the ELA group (8.9% vs 2.2%; p = 0.02). The rate of new pacemaker implantation was 7.0% in the ELA cohort and 15.0% in the control cohort, respectively (p = 0.05)., Conclusion: Treatment of ELA patients with third-generation TAVI prostheses is feasible and safe, providing similar device success and complication rates as in matched controls with regular-sized aortic annulus. Post-interventional pacemaker implantation rates were low compared to the control group, yet incidence of moderate PVL remains problematic in ELA patients., (© 2023. The Author(s).)

Background: Various second-generation transcatheter heart valve (THV) prostheses with high clinical efficacy and safety are available, but there is limited large-scale data available comparing their hemodynamic performance and clinical implications., Objective: To compare the hemodynamic performance and short-term clinical outcome of four second-generation THV prostheses., Methods: 24,124 patients out of the German Aortic Valve Registry who underwent transfemoral transcatheter aortic valve implantation (TAVI) (Evolut™ R n = 7028, Acurate neo™ n = 2922, Portico n = 878 and Sapien 3 n = 13,296) were included in this analysis. Propensity-score weighted analysis was performed to control for differences in age, left ventricular function, STS score and sex. Primary endpoint was survival at one-year, secondary endpoints were 30 days survival, pre-discharge transvalvular gradients, paravalvular leakage and peri-procedural complications., Results: Thirty-day and one-year survival were not significantly different between the four patient groups. Transvalvular gradients in Evolut™ R and Acurate neo™ were significantly lower as compared to Portico and Sapien 3 at hospital discharge. This difference exists across all annulus sizes. Paravalvular leakage ≥ II occurred significantly less often in the Sapien 3 group (1.2%, p < 0.0001). Rate of severe procedural complications was low and comparable in all groups. Permanent pacemaker implantation rate at one year was lowest in the ACUARATE neo group (13.0%) and highest in the Evolut™ R group (21.9%)., Conclusion: Albeit comparable short-term clinical outcomes there are certain differences regarding hemodynamic performance and permanent pacemaker implantation rate between currently available THV prostheses which should be considered for individual prosthesis selection., (© 2023. The Author(s).)

Background: History of cancer is common in patients undergoing transcatheter mitral valve repair (TMVR)., Objectives: Aim was to examine the impact of cancer history on outcomes after TMVR., Methods: In patients of a monocentric prospective registry of TMVR history of cancer was retrospectively assessed from records. Associations with 6-week functional outcomes and clinical outcomes during a median follow-up period of 594 days were examined., Results: Of 661 patients (mean age 79 years; age-range 37-101 years; 56.1% men), 21.6% had a history of cancer with active disease in 4.1%. Compared with non-cancer patients, cancer patients had a similar procedural success rate (reduction of mitral regurgitation to grade 2 or lower 91.6% vs. 88%; p = 0.517) and similar relevant improvement in 6-min walking distance, NYHA class, Minnesota Living with Heart Failure Questionnaire score and Short Form 36 scores. 1-year survival (83% vs. 82%; p = 0.813) and 1-year survival free of heart failure decompensation (75% vs. 76%; p = 0.871) were comparable between cancer and non-cancer patients. Patients with an active cancer disease showed significantly higher mortality compared with patients having a history of cancer (hazard ratio 2.05 [95% CI 1.11-3.82; p = 0.023]) but similar mortality at landmark analysis of 1 year., Conclusion: TMVR can be performed with equal efficacy in patients with and without cancer and symptomatic mitral regurgitation. Cancer patients show comparable clinical outcome and short-term functional improvement as non-cancer patients. However, longterm mortality was increased in patients with active cancer underlining the importance of patient selection within the heart-team evaluation., (© 2023. The Author(s).)

Background: We previously reported procedural and 30-day outcomes of a German early multicenter experience with the PASCAL system for severe mitral regurgitation (MR). This study reports 1-year outcomes of mitral valve transcatheter edge-to-edge repair with the PASCAL system according to MR etiology in a large all-comer cohort., Methods and Results: Clinical and echocardiographic outcomes up to 1-year were investigated according to MR etiology (degenerative [DMR], functional [FMR], or mixed [MMR]) in the first 282 patients with symptomatic MR 3+/4+ treated with the PASCAL implant at 9 centers in 2019. A total of 282 patients were included (33% DMR, 50% FMR, 17% MMR). At discharge, MR reduction to ≤1+/2+ was achieved in 58%/87% of DMR, in 75%/97% of FMR, and in 78%/98% of patients with MMR ( P =0.004). MR reduction to ≤1+/2+ was sustained at 30 days (50%/83% DMR, 67%/97% FMR, 74%/100% MMR) and at 1 year (53%/78% DMR, 75%/97% FMR, 67%/91% MMR) with significant differences between etiologies. DMR patients with residual MR 3+/4+ at 1-year had at least complex valve morphology in 91.7%. Valve-related reintervention was performed in 7.4% DMR, 0.7% FMR, and 0.0% MMR ( P =0.010). At 1-year, New York Heart Association Functional Class was significantly improved irrespective of MR etiology ( P <0.001)., Conclusions: In this large all-comer cohort, mitral valve transcatheter edge-to-edge repair with the PASCAL system was associated with an acute and sustained MR reduction at 1-year in all causes. However, in patients with DMR, MR reduction was less pronounced, reflecting the high incidence of complex or very complex anatomies being referred for mitral valve transcatheter edge-to-edge repair.

Background: Previous trials investigating antithrombotic therapy with a direct oral anticoagulant (DOAC) and a P2Y12 inhibitor after percutaneous coronary intervention (PCI), termed dual therapy, allowed a short period of triple therapy including a DOAC, a P2Y12 inhibitor, and aspirin., Aims: This study aimed to determine whether discontinuation of aspirin on the first post-procedural day is safe or causes ischemic events., Methods: Ischemic and bleeding events during hospitalization were investigated retrospectively in all patients treated with dual therapy (DOAC + P2Y 12 inhibitor, designated as group 1) or triple therapy (DOAC + P2Y 12 inhibitor+aspirin, designated as group 2) from day 1 after PCI at our center., Results: Of 4,564 consecutive PCI procedures, 1,059 (23.2%) had an indication for OAC. Of these, 322 met the inclusion criteria for group 1 and 62 for group 2. Baseline characteristics, CHA 2 DS 2 -VASc and HAS-BLED scores showed no relevant differences between the two groups, and the main indication for DOAC therapy was atrial fibrillation in both groups. Approximately ¼ of patients were treated for acute coronary syndrome. The mean length of post-procedural hospitalization was 2.1 ± 2.5 and 2.2 ± 3.0 days in group 1 and 2, respectively ( p  = 0.305). One patient per group suffered a TIA ( p  = 0.297). There were no other ischemic events and no statistically significant differences in bleeding events. A subgroup analysis of cases hospitalized for ≥2 post-procedural days (group 1: 100 cases, mean 4.4 ± 3.4 days vs. group 2: 25 cases, mean 4.0 ± 4.1 days) confirmed these results., Conclusion: The initiation of dual therapy and thus discontinuation of aspirin on the first postprocedural day appears to be safe with respect to short-term ischemic events in a real-world population. Almost ¼ of patients undergoing PCI have an indication for OAC, highlighting the relevance of this issue., Competing Interests: PS received a travel grant from Bayer Vital GmbH. CH received lecture and consulting fees from Bayer Vital GmbH, Bristol-Myers Squibb/Pfizer, and Daiichi Sankyo. SB received lecture and consulting fees from Bayer Vital GmbH, Pfizer, and Daiichi Sankyo. MH received lecture and consulting fees from Bayer Vital GmbH and Bristol-Myers Squibb/Pfizer. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 von Stein, Seitz, Wienemann, Hohmann, Baar, Baldus and Halbach.)

Background: Favorable 6-month outcomes from the CLASP IID Registry (Edwards PASCAL transcatheter valve repair system pivotal clinical trial) demonstrated that mitral valve transcatheter edge-to-edge repair with the PASCAL transcatheter valve repair system is safe and beneficial for treating prohibitive surgical risk degenerative mitral regurgitation (DMR) patients with complex mitral valve anatomy., Objectives: The authors sought to assess 1-year safety, echocardiographic and clinical outcomes from the CLASP IID Registry., Methods: Patients with 3+ or 4+ DMR who were at prohibitive surgical risk, had complex mitral valve anatomy based on the MitraClip Instructions for Use, and deemed suitable for treatment with the PASCAL system were enrolled prospectively. Safety, clinical, echocardiographic, functional, and quality-of-life outcomes were assessed at 1 year. Study oversight included a central screening committee, echocardiographic core laboratory, and clinical events committee., Results: Ninety-eight patients were enrolled. One-year Kaplan-Meier (KM) estimates of freedom from composite major adverse events, all-cause mortality, and heart failure hospitalization were 83.5%, 89.3%, and 91.5%, respectively. Significant mitral regurgitation (MR) reduction was achieved at 1 year (P < 0.001 vs baseline) including 93.2% at MR ≤2+ and 57.6% at MR ≤1+ with improvements in related echocardiographic measures. NYHA functional class and Kansas City Cardiomyopathy Questionnaire score also improved significantly (P < 0.001 vs baseline)., Conclusions: At 1 year, treatment with the PASCAL system demonstrated safety and significant MR reduction, with continued improvement in clinical, echocardiographic, functional, and quality-of-life outcomes, illustrating the value of the PASCAL system in the treatment of prohibitive surgical risk patients with 3+ or 4+ DMR and complex mitral valve anatomy., Competing Interests: Funding Support and Author Disclosures Dr Smith is on the CLASP IID Trial leadership team and has received institutional grant and travel support for device evaluation from Edwards Lifesciences; has received institutional grants from Artivion; and honoraria for speaking from Artivion and Medtronic. Dr Lim is a consultant for Opus, Nyra, Philips, Venus, and Valgen; and has received research grants from Abbott, Boston Scientific, Corvia, Edwards Lifesciences, Medtronic, V Wave, and WL Gore. Dr Gillam is a consultant for Philips, Bracco, and Edwards Lifesciences; and directs an echocardiography core laboratory for Abbott, Edwards Lifesciences, and Medtronic for which she receives no direct compensation. Dr Zahr is a consultant and has received research grants from Edwards Lifesciences. Dr Chadderdon is an educational consultant for Edwards Lifesciences and Medtronic. Dr Makkar is a consultant and has received research grants from Edwards Lifesciences, Abbott, Medtronic, and Boston Scientific. Dr Goldman consults in minimally invasive mitral valve observation for Edwards Lifesciences. Dr Rudolph has received research grants from Edwards Lifesciences, Abbott, and Boston Scientific. Dr Hermiller is a consultant and proctor for Edwards Lifesciences. Dr Dhoble is a consultant and proctor for Edwards Lifesciences and Abbott. Dr Smalling has received clinical trial grant support from Edwards Lifesciences, Medtronic, and Abbott; and serves as a consultant for Abbott. Dr Latib is a consultant and serves on the advisory board for Boston Scientific, Edwards Lifesciences, Medtronic, Abbott, and Philips. Dr Kodali is a consultant for Admedus, Dura Biotech, TriCares, Phillips, and TriFlo; has received institutional research funding from Edwards Lifesciences, Medtronic, Abbott, Boston Scientific, and JenaValve; and serves on a scientific advisory board and has received equity from Dura Biotech, MicroInterventional Devices, Thubrikar Aortic Valve Inc, Supira, Admedus, TriFlo, Adona, Tioga, and X-Dot. Dr Lurz has received institutional grants from Edwards Lifesciences, Abbott, and ReCor. Dr O’Neill is a consultant for Abiomed, BSCI, and Abbott; and was previously a consultant for Edwards Lifesciences. Dr Laham is a speaker for Abbott, Edwards Lifesciences, and Medtronic. Dr Kar is a consultant for Abbott, Medtronic, Boston Scientific, WL Gore, Laminar, Intershunt, and V wave; has received institutional research grants from Abbott, Medtronic, Boston Scientific, Edwards Lifesciences, and Highlife; is the co-national principal investigator for the REPAIR MR Trial and EXPAND registry and co-national principal investigator for the PINNACLE FLX Trial and CHAMPION Trial; serves on the steering committee for the Triluminate Trial; and is an executive committee member for the RELIEVE HF Trial. Dr Schofer has received travel support from Edwards Lifesciences and Abbott/St. Jude Medical; has received speaker honoraria from Edwards Lifesciences and Boston Scientific; and is a consultant for Edwards Lifesciences and Abbott. Dr Inglessis-Azuaje is a proctor for Edwards Lifesciences and Medtronic; and serves as a lecturer for Edwards Lifesciences and Boston Scientific. Dr Baldus has received research funding from Abbott; and has received lecturing fees from Edwards Lifesciences, Abbott, and Medtronic. Dr Szerlip is a proctor for Edwards Lifesciences and Abbott; is a speaker for Edwards Lifesciences and Boston Scientific; serves as a national principal investigator for an early feasibility study for Edwards Lifesciences; serves on the advisory board for Abbott; and is part of a steering committee for Medtronic. Dr Kliger is a consultant for and has received speaker honoraria from Edwards Lifesciences, Medtronic, and Siemens. Dr Webb is a consultant and national principal investigator for Edwards Lifesciences–sponsored clinical studies; and has received speaking honoraria, travel support, or grant support from Edwards Lifesciences. Dr von Bardeleben is a principal investigator for Phase 3, post-market clinical trials and investigator-initiated trials (Reshape II HF, TENDER, EuroSMR and other registries) for Abbott, Daiichi Sankyo, Edwards Lifesciences, Medtronic, Neochord, Philips and Siemens. Dr Ruf has received speaker, consulting, and proctoring fees from Abbott Laboratories and Edwards Lifesciences. Dr Guerrero has received grant support, and consulting and proctoring fees from Edwards Lifesciences. Dr McCabe is a consultant and has received honoraria from Edwards Lifesciences, Medtronic, Boston Scientific, and Abbott; and holds equity in Excision Medical. Dr Davidson is a consultant and has received research grant support from Edwards Lifesciences. Dr Shah has received grant support, consulting, and proctoring fees from Edwards Lifesciences. Dr Yadav is a consultant and speaker for Edwards Lifesciences, Abbott, Dasi Simulations, and Shockwave Medical. Dr Koulogiannis is a consultant and advisory board member for Edwards Lifesciences; and is a speaker for Abbott. Dr Marcoff serves as a member of the echocardiography core laboratory for Edwards Lifesciences and Abbott for which he receives no direct compensation. Dr Hausleiter is a consultant, and receives speaker honoraria and institutional research support from Edwards Lifesciences. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023. Published by Elsevier Inc.)

Background: Coronary artery disease (CAD) is frequently diagnosed in patients with aortic valve stenosis. Treatment options include surgical and interventional approaches. We therefore analyzed short-term outcomes of patients undergoing either coronary artery bypass grafting with simultaneous aortic valve replacement (CABG + AVR) or staged percutaneous coronary intervention and transcatheter aortic valve implantation (PCI + TAVI)., Methods: From all patients treated since 2017, we retrospectively identified 237 patients undergoing TAVI within 6 months after PCI and 241 patients undergoing combined CABG + AVR surgery. Propensity score matching was performed, resulting in 101 matched pairs., Results: Patients in the CABG + AVR group were younger compared with patients in the PCI + TAVI group (71.9 ± 4.9 vs 81.4 ± 3.6 years; p  < 0.001). The overall mortality at 30 days before matching was higher after CABG + AVR than after PCI + TAVI (7.8 vs 2.1%; p  = 0.012). The paired cohort was balanced for both groups regarding demographic variables and the risk profile (age: 77.2 ± 3.7 vs78.5 ± 2.7 years; p  = 0.141) and EuroSCORE II (6.2 vs 7.6%; p  = 0.297). At 30 days, mortality was 4.9% in the CABG + AVR group and 1.0% in the PCI + TAVI group ( p  = 0.099). Rethoracotomy was necessary in 7.9% in the CABG + AVR, while conversion to open heart surgery was necessary in 2% in the PCI + TAVI group. The need for new pacemaker was lower after CABG + AVR than after PCI + TAVI (4.1 vs 6.9%; p  = 0.010). No paravalvular leak (PVL) was noted in the CABG + AVR group, while the incidence of moderate-to-severe PVL after PCI + TAVI was 4.9% ( p  = 0.027)., Conclusion: A staged interventional approach comprises a short-term survival advantage compared with combined surgery for management of CAD and aortic stenosis. However, PCI + TAVI show a significantly higher risk of atrioventricular block and PVL. Further long-term trials are warranted., Competing Interests: None declared., (Thieme. All rights reserved.)

Background: Guidelines on myocardial infarction (MI) recommend antithrombotic and anticoagulatory treatment at time of diagnosis. MI with ST segment elevation (STEMI) is mostly a certain diagnosis. Acute coronary syndrome without ST segment elevation (NSTE-ACS) has diagnostic uncertainty and remains a working diagnosis in the prehospital setting., Objective: Assessment of prehospital loading with aspirin and heparin depending on ACS subtype and pretreatment with oral anticoagulants., Methods: The PRELOAD survey was a nationwide German study. STEMI/NSTE-ACS scenarios were designed and varied in pretreatment: I) no pretreatment, II) new oral anticoagulants (NOAC), III) vitamin K antagonist (VKA). Loading strategy was assessed and included: a) aspirin (ASA), b) unfractionated heparin (UFH), c) ASA + UFH, d) no loading., Results: A total of 708 emergency physicians were included. In NSTE-ACS without pretreatment, 79% chose loading (p < 0.001). ASA + UFH (71.4%) was the preferred option. In corresponding STEMI scenario, 100% chose loading and 98.6% preferred ASA + UFH (p < 0.001). In NSTE-ACS with NOAC pretreatment, 69.8% favored loading (p < 0.001); in VKA pretreatment the corresponding rate was 72.3% (p < 0.001). In each scenario, ASA was the preferred option. In STEMI with NOAC pretreatment, 97.5% chose loading (p < 0.001); analogous rate was 96.8% in STEMI with VKA pretreatment (p < 0.001). ASA was the preferred option again., Conclusions: Prehospital loading was the preferred treatment strategy despite the diagnostic uncertainty in NSTE-ACS and guidelines recommending loading at time of diagnosis. Pretreatment with oral anticoagulants resulted in a strategy shift to loading with only aspirin. In STEMI patients, this indicates potential undertreatment., (© 2023. The Author(s).)

Objective: To compare the measurement of aortic diameters using a novel flow-independent MR-Angiography (3D modified Relaxation-Enhanced Angiography without Contrast and Triggering (modified REACT)) and transthoracic echocardiography (TTE) in Marfan syndrome (MFS) patients., Material and Methods: This retrospective, single-center analysis included 46 examinations of 32 MFS patients (mean age 37.5 ± 11.3 years, 17 women, no prior aortic surgery) who received TTE and 3D modified REACT (ECG- and respiratory-triggering, Compressed SENSE factor 9 for acceleration of image acquisition) of the thoracic aorta. Aortic diameters (sinus of Valsalva (SV), sinotubular junction (STJ), and ascending aorta (AoA)) were independently measured by two cardiologists in TTE (leading-edge) and two radiologists in modified REACT (inner-edge, using multiplanar reconstruction). Intraclass correlation coefficient, Bland-Altman analyses, and Pearson's correlation (r) were used to assess agreement between observers and methods., Results: Interobserver correlation at the SV, STJ, and AoA were excellent for both, TTE (ICC = 0.95-0.98) and modified REACT (ICC = 0.99-1.00). There was no significant difference between TTE and modified REACT for diameters measured at the SV (39.24 ± 3.24 mm vs. 39.63 ± 3.76 mm; p = 0.26; r = 0.78) and the STJ (35.16 ± 4.47 mm vs. 35.37 ± 4.74 mm; p = 0.552; r = 0.87). AoA diameters determined by TTE were larger than in modified REACT (34.29 ± 5.31 mm vs. 30.65 ± 5.64 mm; p < 0.01; r = 0.74). The mean scan time of modified REACT was 05:06 min ± 02:47 min, depending on the patient's breathing frequency and heart rate., Conclusions: Both TTE and modified REACT showed a strong correlation for all aortic levels; however, at the AoA, diameters were larger using TTE, mostly due to the limited field of view of the latter with measurements being closer to the aortic valve. Given the excellent interobserver correlation and the strong agreement with TTE, modified REACT represents an attractive method to depict the thoracic aorta in MFS patients., Competing Interests: Declaration of Competing Interest Kilian Weiss: Employee, Philips GmbH. Roman Johannes Gertz: Received research support from Philips Healthcare. David Maintz: Speaker's bureau, Philips Healthcare. Lenhard Pennig: Speaker's bureau, Philips Healthcare. Speaker's bureau, Guerbet GmbH. Henrik ten Freyhaus: Speaker's bureau, Guerbet GmbH, consulting activities, General Electrics. The remaining authors disclose no relevant relationships., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objectives: Left ventricular reverse remodeling (LVRR) is associated with improved outcome in patients with heart failure. Factors associated with and predictive of LVRR in patients with low-flow low-gradient aortic stenosis (LFLG AS) after transcatheter aortic valve implantation (TAVI) and its impact on outcome were assessed., Methods: Pre- and postprocedural left ventricular (LV) function and volume were investigated in 219 patients with LFLG. LVRR was defined as an absolute increase of ≥10% in LV ejection fraction (LVEF) and reduction of ≥15% in LV end-systolic volume (LVESV). The primary endpoint was the combination of all-cause mortality and rehospitalization for heart failure., Results: The mean LVEF was 35.0 ± 10.0%, with a stroke volume index (SVI) of 25.9 ± 6.0 mL/m 2 and LVESV of 94.04 ± 46.0 mL. At a median of 5.2 months (interquartile range, 2.7-8.1 months), 77.2% (n = 169) of the patients showed echocardiographic evidence of LVRR. A multivariate model revealed three independent factors for LVRR after TAVI: SVI of <25 mL/m 2 (hazard ratio [HR], 2.31; 95% confidence interval [CI], 1.08-3.58; p < 0.01), LVEF of <30% (HR, 2.76; 95% CI, 1.53-2.91; p < 0.01), and valvulo-arterial impedance (Z va ) of <5 mmHg/mL/m 2 (HR, 5.36; 95% CI, 1.80-15.98; p < 0.01). Patients without evidence of LVRR showed a significantly higher incidence of the 1-year combined endpoint (32 [64.0%] vs. 75 [44.4%], p < 0.01)., Conclusions: The majority of patients with LFLG AS show LVRR after TAVI, which is associated with favorable outcomes. An SVI of <25 mL/m 2 , LVEF of <30%, and Z va < 5mmHg/mL/m 2 represent predictors of LVRR., (Copyright © 2023 Hellenic Society of Cardiology. Published by Elsevier B.V. All rights reserved.)

Patients with left heart disease (LHD) often display pulmonary hypertension (PH), which impacts morbidity and mortality. The pathophysiology of PH is complex and entails pulmonary congestion due to elevated left-sided filling pressures, pulmonary vasoconstriction as well as vascular remodeling. The recent ESC/ERS Guidelines on pulmonary hypertension updated the hemodynamic definitions of pulmonary hypertension in general, and the subclassification of post-capillary PH. This review summarizes recent advances in the diagnostic work-up and management strategies of PH associated with LHD. Specifically, we summarize revisited hemodynamic definitions and the characteristics of isolated post-capillary PH (IpcPH) and combined post- and pre-capillary PH (CpcPH). Furthermore, we review the current knowledge on the pathogenesis of PH-LHD, the prognostic relevance of hemodynamic parameters, and the management strategies, differentiating between treatment of the underlying left heart disease and therapies targeting the pulmonary circulation. The article emphasises the need for precise diagnostic work-up and individualized treatment strategies in patients with PH-LHD., Competing Interests: MW: Vortragshonorare von Janssen; JA: Vortragshonorare von Janssen und MSD; CH: Honorare für Vorträge und/oder Beratertätigkeiten: Actelion, Bayer, MSD, Pfizer; SR: Honorare für Vorträge und/oder Beratertätigkeiten: Abbott, Acceleron, Actelion, Aerovate, Altavant, AOP Orphan, AstraZeneca, Bayer, Boehringer-Ingelheim, Edwards, Ferrer, Gossamer, Janssen, MSD, United Therapeutics, Vifor; Forschungsunterstützung an Institution: Actelion, AstraZeneca, Bayer, Janssen; JD, LO, TT und SB: keine Interessenkonflikte im Zusammenhang mit diesem Artikel., (Thieme. All rights reserved.)

Objective: After transcatheter aortic valve implantation (TAVI), the optimal regimen of anticoagulant therapy in patients with an additional indication for oral anticoagulation remains a matter of debate. This study investigates the efficacy of direct oral anticoagulants (DOACs) versus vitamin K antagonists (VKAs) in patients after TAVI in a real-world population., Methods: The German Aortic Valve RegistrY (GARY) is a prospective, multicentre registry enrolling patients undergoing invasive treatment for aortic valve disease. From January 2011 to December 2019, 1 41 790 patients from 92 hospitals in Germany were enrolled. Anticoagulatory treatment regimens were assessed at hospital discharge for patients after TAVI procedures. All-cause mortality and the combined endpoint 'cardiac and cerebrovascular events' containing myocardial infarction, stroke, transient ischaemic attack, aortic prosthesis reintervention and all-cause mortality in the first year after TAVI were examined by treatment regimen., Results: Of 45 598 patients (mean age 80.7±5.7 years, 49.3% males) undergoing TAVI, 16 974 patients (37.2%) received an anticoagulant regimen that included VKA or DOAC. Hereof, the majority of patients were prescribed VKA (n=11 333, 66.8%) compared with DOAC (n=5641, 33.2%) with an increase of DOAC use from 9.4% in 2011 to 69.9% in 2019. During the 1-year follow-up, the absolute event rates per 100 person-years for all-cause mortality and the combined endpoint cardiac and cerebrovascular events were 1.9 and 1.3 for VKA-treated and 1.7 and 1.2 for DOAC-treated patients, respectively. After adjustment for baseline confounders, all-cause mortality (HR 0.95, 95% CI 0.88 to 1.01, p=0.114) and cardiac and cerebrovascular event-free survival (HR 0.93, 95% CI 0.86 to 1.01, p=0.071) did not differ significantly between VKA and DOAC groups., Conclusions: This study supports evidence of the efficacy of DOAC use after TAVI in patients with an indication for oral anticoagulation., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Approximately one fifth of patients diagnosed with atrial fibrillation (AF) undergo a percutaneous coronary intervention (PCI). Current guidelines recommend different combinations and durations of triple or dual antithrombotic therapy for these patients but data on the implementation of these recommendations in clinical routine are scarce. ENCOURAGE-AF is a prospective, non-interventional, non-comparative, multicentre study. Approximately 720 patients will be consecutively enrolled from 70 participating sites across Germany. Patients with non-valvular AF treated with edoxaban, who have undergone successful PCI, have no planned elective cardiac intervention during the study period, have capability, availability, and willingness for follow-up by telephone interview during the study, are aged ≥ 18 years with life expectancy ≥ 1 year, and provide written informed consent, will be included. Eligible patients will be enrolled between 4- and 72-h after completing a successful PCI. Duration of exposure to and dosing regimens of edoxaban, antiplatelet agents and other concomitant medications of interest will be monitored in line with the clinical practice. Physician- and patient-reported clinical events, adverse drug reactions, patient quality of life (EQ-5D-5L) and health resource utilisation (HRU) parameters will be evaluated at 30 days and 1-year post-PCI. The ENCOURAGE-AF non-interventional study will provide insights into the patterns of edoxaban usage in combination with antiplatelet treatment and other concomitant medications in AF patients with a successful PCI over a 1-year time period during routine clinical practice in Germany. The effectiveness and safety of edoxaban in this patient population, as well as patients' quality of life and HRU will be evaluated.Trial registration: Clinicaltrial.gov NCT04519944, registered on 20 August 2020., (© 2023. Springer Nature Limited.)

Purpose: Access-related vascular complications in transfemoral transcatheter aortic valve implantation (TAVI) can be treated endovascularly or surgically. The aim of this study was to evaluate the short- and long-term outcomes of endovascular treatment compared with surgical repair for access-related vascular complications., Methods: This retrospective study was performed from January 1, 2018, to December 31, 2020. All transfemorally treated TAVI patients in whom a surgical or endovascular treatment for an access site complication was needed were included. The primary outcome was the need for any related vascular re-operation., Results: In total, 1219 transfemoral TAVI procedures were conducted during the study period. 19 patients suffered an access complication requiring endovascular treatment, while 54 patients required surgical repair. No differences were seen with regard to re-operations (endovascular 15.8% vs surgical 14.8%; p=0.919), wound infections (endovascular 0% vs surgical. 11.1%; p=0.129), and wound healing disorders (endovascular 15.8% vs surgical 29.6%; p=0.237). Patients undergoing endovascular treatment were discharged earlier (endovascular 11.2 vs surgical 14.9 days; p=0.028). After surgical repair, patients received significantly more blood transfusions than endovascularly treated patients (endovascular 1.00 vs surgical 3.1 red blood cell concentrate bags; p<0.001). No differences were found regarding the new onset of walking pain, rest pain, and ischemic ulcers during follow-up., Conclusion: In this retrospective cohort, endovascular treatment of access-related vascular complications of transfemoral TAVI procedures was safe and feasible. During the hospital stay, endovascularly treated patients received fewer blood transfusions and were discharged faster than surgically treated patients. No differences regarding clinical outcomes and re-intervention rates were seen during the follow-up., Clinical Impact: Given the in this retrospective study demonstrated safety and feasibility of endovascular treatment for major access-related vascular complications, along with the in-hospital benefits and absence of follow-up disadvantages compared to surgical treatment, endovascular treatment should be considered in cases of major access-related vascular complications in transfemoral TAVI patients., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.