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Worldwide, valvular heart disease (VHD) is a common cause of hospitalization for acute heart failure. In acute heart failure caused by VHD, symptoms result from rapid haemodynamic changes and subsequent decline in cardiac function, and if left untreated, leads to acute decompensation and cardiogenic shock. Current evidence remains scarce and recommendations regarding the management of acute heart failure caused by VHD are lacking in most recent international guidelines. Herein, we review the management of acute heart failure caused by VHD with a focus on transcatheter therapies and describe currently available evidence based on a systematic literature search on the following valve pathologies: (i) aortic stenosis, (ii) aortic regurgitation, (iii) mitral regurgitation, and (iv) mitral stenosis. Articles reporting outcomes following urgent or emergent valve intervention in the setting of cardiogenic shock or acute heart failure were considered. After screening a total of 2234 articles, 76 published between 1994 and 2023 were included in subsequent analysis. Based on available evidence, proposed treatment algorithms to guide optimal management of acute heart failure caused by VHD were created. As the number of patients presenting with acute heart failure caused by VHD continues to rise and outcomes following transcatheter valve interventions continue to improve, it is inevitable that minimally invasive options will play an increasingly important role in the acute setting, especially given these patients are at an increased operative risk. This review aims to present an organized approach to the complex management and interventional treatment of patients with acute heart failure caused by VHD., (© 2024 European Society of Cardiology.)

Aims: Right ventricular reverse remodelling (RVRR) is linked to improved survival in patients with severe tricuspid regurgitation (TR) and right-sided heart failure who underwent interventional treatment. However, the role of residual TR on RVRR remains unclear. In this analysis the impact of residual TR on RVRR after interventional TR treatment, which was validated by two independent cohorts at four sites using echocardiography or cardiac magnetic resonance (CMR) imaging, was investigated., Methods and Results: Overall, 253 patients who were treated for severe TR and right-sided heart failure using different treatment modalities (tricuspid transcatheter edge-to-edge repair [T-TEER], transcatheter tricuspid valve annuloplasty, orthotopic transcatheter TV replacement [TTVR], heterotopic TTVR) were included. Three-dimensional echocardiographic and CMR-based assessment of RVRR and clinical evaluation of decongestion or exercise capacity were performed at baseline and 30 days after the procedure. Mortality was analysed at 1 year after transcatheter tricuspid valve intervention (TTVI). In patients with residual TR ≤1+ pronounced reduction of right ventricular end-diastolic and end-systolic volumes was observed. In patients with residual TR ≥2+ the effect of RVRR gradually decreased with higher residual TR reinforcing the relevance of optimal procedural results for RVRR. These findings were validated in two independent cohorts. In contrast to RVRR, residual TR ≤1+ and 2+ were associated with similar 1-year survival. RVRR was only observed after T-TEER or orthotopic TTVR, but not after heterotopic TTVR as expected. However, all three treatment modalities were accompanied by significant decongestion and functional improvement at 30-day follow-up., Conclusion: In patients with severe TR and right-sided heart failure undergoing TTVI, superior procedural results were associated with more pronounced RVRR., (© 2024 The Author(s). European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background: It is estimated that 6% of persons over age 75 have clinically relevant tricuspid regurgitation (TR). This condition carries a high mortality and is of particular interest because of the recent development of new interventional treatments., Methods: This review is based on publications that were retrieved by a selective search in the PubMed database for randomized controlled trials (RCTs), observational studies, registry studies, expert recommendations, and current international guidelines., Results: The evidence reveals that TR is an independent cause of mortality. Mortality is correlated with the severity of TR: approximately 35% of patients with severe TR and right heart failure die within 1 year, and about 60% within 3 years. The clinical course varies depending on the etiology (primary TR, atrial/ventricular secondary TR, association with pacemaker systems). In the outpatient setting, timely diagnosis by transthoracic echocardiography is crucial. The options for pharmacotherapy are essentially limited to diuretic treatment (grade 2a recommendation). Early referral to a specialized heart valve center is essential for the prevention of irreversible damage of the right heart and secondary end-organ damage, including cardiohepatic and cardiorenal syndromes. In the heart valve center, an extended diagnostic evaluation with multimodal imaging is followed by a case discussion by the interdisciplinary cardiac team, with individual evaluation of the treatment options. The first randomized controlled trial of treatment for TR yielded a win ratio of 1.48 (95% confidence interval, [1.06; 2.13]) for interventional treatment (edge-to-edge repair) compared to optimal medical therapy., Conclusion: As the understanding of tricuspid regurgitation improves, strategies for its interventional treatment are undergoing steady development, with the aim of lowering the mortality of this condition.

Background: Right-sided heart failure (HF) due to severe tricuspid regurgitation (TR) is associated with reduced quality of life (QoL). Here, we analyzed the impact of TR on specific QoL dimensions and the effect of transcatheter tricuspid valve intervention (TTVI) on individual QoL items., Methods and Results: In this study, we included 174 patients with HF (49% women; median age, 79 years; 97% New York Heart Association ≥3) with baseline QoL assessment undergoing TTVI by transcatheter edge-to-edge-repair at our center between April 2016 and March 2022. QoL was assessed by the standardized Minnesota Living With HF Questionnaire. QoL change after TTVI and correlation to functional end points were analyzed. In addition, all QoL domains and the 21 individual items of the Minnesota Living With HF Questionnaire were analyzed. TTVI significantly reduced TR (TR ≥3: baseline 95%, 1-year-follow-up 7%; P <0.001). Total Minnesota Living with HF Questionnaire score improved from 37 (interquartile range, 26-50) points to 31 (interquartile range, 17-42) points (median follow-up-interval, 355 days; P <0.001). QoL improvement was associated with positive New York Heart Association class, 6-minute walking distance, and actigraphy changes (all P <0.05). The detailed analysis revealed that all items of the physical-related QoL dimension were impaired at baseline and strongly improved after TTVI. In contrast, the emotional and "social" Minnesota Living With HF Questionnaire dimensions were largely unaffected at baseline, yet specific items improved with TTVI., Conclusions: In this single-center study, we delineate the QoL-associated disease burden of TR and identify specific QoL items that improved after TTVI. Our findings support TTVI in patients with reduced QoL and may add to the development of specific tools assessing the functional status of an increasing patient population undergoing TTVI.

Aims: Data on the prognostic impact of residual tricuspid regurgitation (TR) after tricuspid transcatheter edge-to-edge repair (T-TEER) are scarce. The aim of this analysis was to evaluate 2-year survival and symptomatic outcomes of patients in relation to residual TR after T-TEER., Methods and Results: Using the large European Registry of Transcatheter Repair for Tricuspid Regurgitation (EuroTR registry) we investigated the impact of residual TR on 2-year all-cause mortality and New York Heart Association (NYHA) functional class at follow-up. The study further identified predictors for residual TR ≥3+ using a logistic regression model. The study included a total of 1286 T-TEER patients (mean age 78.0 ± 8.9 years, 53.6% female). TR was successfully reduced to ≤1+ in 42.4%, 2+ in 40.0% and 3+ in 14.9% of patients at discharge, while 2.8% remained with TR ≥4+ after the procedure. Residual TR ≥3+ was an independent multivariable predictor of 2-year all-cause mortality (hazard ratio 2.06, 95% confidence interval 1.30-3.26, p = 0.002). The prevalence of residual TR ≥3+ was four times higher in patients with higher baseline TR (vena contracta >11.1 mm) and more severe tricuspid valve tenting (tenting area >1.92 cm 2 ). Of note, no survival difference was observed in patients with residual TR ≤1+ versus 2+ (76.2% vs. 73.1%, p = 0.461). The rate of NYHA functional class ≥III at follow-up was significantly higher in patients with residual TR ≥3+ (52.4% vs. 40.5%, p < 0.001). Of note, the degree of TR reduction significantly correlated with the extent of symptomatic improvement (p = 0.012)., Conclusions: T-TEER effectively reduced TR severity in the majority of patients. While residual TR ≥3+ was associated with worse outcomes, no differences were observed for residual TR 1+ versus 2+. Symptomatic improvement correlated with the degree of TR reduction., (© 2024 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Transcatheter tricuspid valve replacement (TTVR) is an increasingly used treatment technique for patients with severe tricuspid regurgitation (TR). Currently, available data from international registries and randomized controlled trials provide outcome data until a maximum follow-up of 2 years after the procedure. This case report presents 4-year follow-up data for an 84-year-old woman who underwent TTVR for torrential TR in 2019. The patient experienced durable TR reduction, symptomatic improvement, right ventricular reverse remodeling, and substantial improvement in liver and kidney function., Competing Interests: Dr Stolz has received speaker honoraria from Edwards Lifesciences. Dr Hausleiter has received research support and speaker honoraria from Edwards Lifesciences. Dr Näbauer has received speaker fees from Abbott Vascular and Edwards Lifesciences. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2024 The Authors.)

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.)

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.)

Mitral valve transcatheter edge-to-edge repair (M-TEER) and replacement (TMVR) have evolved as guideline-recommended treatment approaches for mitral regurgitation (MR). Even though they are supported by a growing body of evidence from either randomized trials or large registries, there are still several unsolved challenges in the field of interventional MR treatment. In the present review, we discuss the ten most important open questions regarding M-TEER and TMVR.

We present 2 cases of significant mitral regurgitation secondary to pericardial patch avulsion from the anterior mitral valve leaflet after aortic valve replacement with aortic annulus enlargement. Both cases were successfully managed by transcatheter repair with off-label implantation of occluder devices., Competing Interests: Dr Stocker has served as a consultant for Occlutech International. Dr Hausleiter has received speaker honoraria from and serves as consultant for Edwards Lifesciences. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2023 The Authors.)

Background: Concomitant moderate/severe mitral regurgitation (MR) is observed in 17-35% of patients undergoing transcatheter aortic valve implantation (TAVI) and contributes to a worse prognosis. Studies analysing outcomes in patients undergoing TAVI with different MR aetiologies, including atrial functional MR (aFMR), are lacking., Aims: We aimed to analyse outcomes and changes in MR severity in patients with aFMR, ventricular functional (vFMR) and primary mitral regurgitation (PMR) following TAVI., Methods: We analysed all consecutive patients with at least moderate MR undergoing TAVI between January 2013 and December 2020 at the Munich University Hospital. Characterisation of MR aetiology was performed by detailed individual echocardiographic assessment. Three-year mortality, changes in MR severity and New York Heart Association (NYHA) Functional Class at follow-up were assessed., Results: Out of 3,474 patients undergoing TAVI, 631 patients showed MR ≥2+ (172 with aFMR, 296 with vFMR, 163 with PMR). Procedural characteristics and endpoints were comparable between groups. The rate of MR improvement was 80.2% in aFMR patients, which was significantly higher compared to both other groups (vFMR: 69.4%; p=0.03; PMR: 40.8%; p<0.001). The estimated 3-year survival rates did not differ between aetiologies (p=0.57). However, MR persistence at follow-up was associated with increased mortality (hazard ratio 1.49, 95% confidence interval: 1.04-2.11; p=0.027), mainly driven by the PMR subgroup of patients. NYHA Class improved significantly in all groups. In patients with baseline MR ≥3+, the PMR aetiology was associated with the lowest MR improvement, the lowest survival rates and least symptomatic improvement., Conclusions: TAVI reduces MR severity and symptoms in patients with aFMR, vFMR and less-pronounced PMR. The presence of aFMR was associated with the greatest MR severity improvement.

Aims: The impact of the cardio-hepatic syndrome (CHS) on outcomes in patients undergoing mitral valve transcatheter edge-to-edge repair (M-TEER) for relevant mitral regurgitation (MR) is unknown. The objectives of this study were three-fold: (i) to characterize the pattern of hepatic impairment, (ii) to investigate the prognostic value of CHS, and (iii) to evaluate the changes in hepatic function after M-TEER., Methods and Results: Hepatic impairment was quantified by laboratory parameters of liver function. In accordance with existing literature, two types of CHS were distinguished: ischaemic type I CHS (elevation of both transaminases) and cholestatic type II CHS (elevation of two out of three parameters of hepatic cholestasis). The impact of CHS on 2-year mortality was evaluated using a Cox model. The change in hepatic function after M-TEER was assessed by laboratory testing at follow-up. We analysed 1083 patients who underwent M-TEER for relevant primary or secondary MR at four European centres between 2008 and 2019. Ischaemic type I and cholestatic type II CHS were observed in 11.1% and 23.0% of patients, respectively. Predictors for 2-year all-cause mortality differed by MR aetiology. While in primary MR cholestatic type II CHS was independently associated with 2-year mortality, ischaemic CHS type I was an independent mortality predictor in secondary MR patients. At follow-up, patients with MR reduction ≤2+ (obtained in 90.7% of patients) presented with improved parameters of hepatic function (median reduction of 0.2 mg/dl, 0.2 U/L and 21 U/L for bilirubin, alanine aminotransferase and gamma-glutamyl transferase, respectively, p < 0.01)., Conclusions: The CHS is frequently observed in patients undergoing M-TEER and significantly impairs 2-year survival. Successful M-TEER may have beneficial effects on CHS., (© 2023 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background: Men and women differ regarding comorbidities, pathophysiology, and the progression of valvular heart diseases., Objectives: This study sought to assess sex-related differences regarding clinical characteristics and the outcome of patients with severe tricuspid regurgitation (TR) undergoing transcatheter tricuspid valve intervention (TTVI)., Methods: All 702 patients in this multicenter study underwent TTVI for severe TR. The primary outcome was 2-year all-cause mortality., Results: Among 386 women and 316 men in this study, men were more often diagnosed with coronary artery disease (52.9% in men vs 35.5% in women; P = 5.6 × 10 -6 ). Subsequently, the underlying etiology for TR in men was predominantly secondary ventricular (64.6% in men vs 50.0% in women; P = 1.4 × 10 -4 ), whereas women more often presented with secondary atrial etiology (41.7% in women vs 24.4% in men, P = 2.0 × 10 -6 ). Notably, 2-year survival after TTVI was similar in women and men (69.9% in women vs 63.7% in men; P = 0.144). Multivariate regression analysis identified dyspnea expressed as New York Heart Association functional class, tricuspid annulus plane systolic excursion (TAPSE), and mean pulmonary artery pressure (mPAP) as independent predictors for 2-year mortality. The prognostic significance of TAPSE and mPAP differed between sexes. Consequently, we looked at right ventricular-pulmonary arterial coupling expressed as TAPSE/mPAP and identified sex-specific thresholds to best predict survival; women with a TAPSE/mPAP ratio <0.612 mm/mm Hg displayed a 3.43-fold increased HR for 2-year mortality (P < 0.001), whereas men with a TAPSE/mPAP ratio <0.434 mm/mm Hg displayed a 2.05-fold increased HR for 2-year mortality (P = 0.001)., Conclusions: Even though men and women differ in the etiology of TR, both sexes show similar survival rates after TTVI. The TAPSE/mPAP ratio can improve prognostication after TTVI, and sex-specific thresholds should be applied to guide future patient selection., Competing Interests: Funding Support and Author Disclosures Dr Lachmann has received funding from the Technical University of Munich (Clinician Scientist Grant) and from the Else Kröner-Fresenius Foundation (Clinician Scientist Grant). All authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Guideline-directed medical therapy (GDMT) optimization is mandatory before transcatheter edge-to-edge mitral valve repair (M-TEER) in patients with secondary mitral regurgitation (SMR) and heart failure (HF) with reduced ejection fraction (HFrEF). However, the effect of M-TEER on GDMT is unknown., Objectives: The authors sought to evaluate frequency, prognostic implications and predictors of GDMT uptitration after M-TEER in patients with SMR and HFrEF., Methods: This is a retrospective analysis of prospectively collected data from the EuroSMR Registry. The primary events were all-cause death and the composite of all-cause death or HF hospitalization., Results: Among the 1,641 EuroSMR patients, 810 had full datasets regarding GDMT and were included in this study. GDMT uptitration occurred in 307 patients (38%) after M-TEER. Proportion of patients receiving angiotensin-converting enzyme inhibitors/angiotensin receptor blockers/angiotensin receptor-neprilysin inhibitors, beta-blockers, and mineralocorticoid receptor antagonists was 78%, 89%, and 62% before M-TEER and 84%, 91%, and 66% 6 months after M-TEER (all P < 0.001). Patients with GDMT uptitration had a lower risk of all-cause death (adjusted HR: 0.62; 95% CI: 0.41-0.93; P = 0.020) and of all-cause death or HF hospitalization (adjusted HR: 0.54; 95% CI: 0.38-0.76; P < 0.001) compared with those without. Degree of MR reduction between baseline and 6-month follow-up was an independent predictor of GDMT uptitration after M-TEER (adjusted OR: 1.71; 95% CI: 1.08-2.71; P = 0.022)., Conclusions: GDMT uptitration after M-TEER occurred in a considerable proportion of patients with SMR and HFrEF and is independently associated with lower rates for mortality and HF hospitalizations. A greater decrease in MR was associated with increased likelihood for GDMT uptitration., Competing Interests: Funding Support and Author Disclosures Dr Adamo has received speaker fees from Abbott Vascular and Medtronic. Dr Baldus has received lecture fees and research support from Abbott and Edwards Lifesciences. Dr Kalbacher has received speaker honoraria from Abbott; and has received travel expenses and proctor fees from Edwards Lifesciences. Dr Lurz has received institutional research grants from Edwards Lifesciences and Abbott Vascular. Dr Petronio has been a consultant for Abbott Vascular, Boston Scientific, and Medtronic. Dr von Bardeleben has served on trial steering committees (unpaid) for Abbott, Edwards Lifesciences, Medtronic, and Neochord; and has served on advisory boards for and received speaker fees from Abbott, Edwards Lifesciences, Medtronic, Neochord, Philips, and Siemens. Dr Windecker has received institutional research, travel, or educational grants from Abbott, Abiomed, Amgen, AstraZeneca, Bayer, Biotronik, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb, Cardinal Health, CardioValve, Corflow Therapeutics, CSL Behring, Daiichi Sankyo, Edwards Lifesciences, Guerbet, InfraRedx, Janssen-Cilag, Johnson & Johnson, Medicure, Medtronic, Merck Sharp & Dohm, Miracor Medical, Novartis, Novo Nordisk, Organon, OrPha Suisse, Pfizer, Polares, Regeneron, Sanofi, Servier, Sinomed, Terumo, Vifor, and V-Wave; has served as advisory board member and/or member of the steering/executive group of trials funded by Abbott, Abiomed, Amgen, AstraZeneca, Bayer, Boston Scientific, Biotronik, Bristol Myers Squibb, Edwards Lifesciences, Janssen, MedAlliance, Medtronic, Novartis, Polares, Recardio, Sinomed, Terumo, V-Wave, and Xeltis with payments to his institution; and has been an unpaid member of the steering/executive committee groups of several investigator-initiated trials that receive funding by industry. Dr Hausleiter has received speaker honoraria from Abbott Vascular. Prof Metra has received consulting honoraria for participation in steering committees or advisory boards or for speeches from Abbott Vascular, Amgen, AstraZeneca, Bayer, Edwards Lifesciences, Fresenius, Novartis, and Servier. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background Tricuspid regurgitation (TR) frequently develops in patients with long-standing pulmonary hypertension, and both pathologies are associated with increased morbidity and mortality. This study aimed to improve prognostic assessment in patients with severe TR undergoing transcatheter tricuspid valve intervention (TTVI) by relating the extent of TR to pulmonary artery pressures. Methods and Results In this multicenter study, we included 533 patients undergoing TTVI for moderate-to-severe or severe TR. The proportionality framework was based on the ratio of tricuspid valve effective regurgitant orifice area to mean pulmonary artery pressure. An optimal threshold for tricuspid valve effective regurgitant orifice area/mean pulmonary artery pressure ratio was derived on 353 patients with regard to 2-year all-cause mortality and externally validated on 180 patients. Patients with a tricuspid valve effective regurgitant orifice area/mean pulmonary artery pressure ratio ≤1.25 mm 2 /mm Hg (defining proportionate TR) featured significantly lower 2-year survival rates after TTVI than patients with disproportionate TR (56.6% versus 69.6%; P =0.005). In contrast with patients with disproportionate TR (n=398), patients with proportionate TR (n=135) showed more pronounced mPAP levels (37.9±9.06 mm Hg versus 27.9±8.17 mm Hg; P <2.2×10 -16 ) and more severely impaired right ventricular function (tricuspid annular plane systolic excursion: 16.0±4.11 versus 17.0±4.64 mm; P =0.012). Moreover, tricuspid valve effective regurgitant orifice area was smaller in patients with proportionate TR when compared with disproportionate TR (0.350±0.105 cm 2 versus 0.770±0.432 cm 2 ; P <2.2×10 -16 ). Importantly, proportionate TR remained a significant predictor for 2-year mortality after adjusting for demographic and clinical variables (hazard ratio, 1.7; P =0.006). Conclusions The proposed proportionality framework promises to improve future risk stratification and clinical decision-making by identifying patients who benefit the most from TTVI (disproportionate TR). As a next step, randomized controlled studies with a conservative treatment arm are needed to quantify the net benefit of TTVI in patients with proportionate TR.

Objectives: Severe mitral regurgitation (MR) and tricuspid regurgitation (TR) aggravate haemodynamic stress leading to congestive heart failure with impaired hepatic function, also known as cardiohepatic syndrome (CHS). Current perioperative risk calculators do not sufficiently consider CHS and serum liver function parameters lack sensitivity to diagnose CHS. Indocyanine green and its elimination (measured by the LIMON® test) represent a dynamic and non-invasive test which correlates with the hepatic function. Nevertheless, its utility in the setting of transcatheter valve repair/replacement (TVR) to predict CHS and outcome remains unknown., Methods: We analysed liver function and outcomes of patients undergoing TVR for MR or TR between August 2020 and May 2021 at the Munich University Hospital., Results: Out of a total of 44 patients treated at the University Hospital of Munich, 21 (48%) were treated for severe MR, 20 (46%) for severe TR and 3 (7%) for both diseases. Procedural success defined as MR/TR ≤2+ was 94% among MR patients and 92% among TR patients. While classical serum liver function parameters did not change after TVR, there was a significant improvement in liver function as assessed by the LIMON® test (P ≤ 0.001). Patients with baseline indocyanine green plasma disappearance rate <12.95%/min showed significantly increased 1-year mortality (hazard ratio: 1.54, 95% confidence interval: 1.05-2.25, P = 0.027) and lower New York Hear Association class improvement (P = 0.05)., Conclusions: Especially in the context of the recently stressed importance of a careful patient selection prior to the interdisciplinary treatment of valvular heart disease, the LIMON® test may provide further real-time information on the patients' cardiohepatic injury and prognosis., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery.)

Introduction: Mitral regurgitation (MR) is associated with substantial morbidity and mortality. Within the past 15 years, mitral valve edge-to-edge repair (M-TEER) has developed from an experimental approach to a guideline-recommended, safe, and effective treatment option for patients with severe primary or secondary mitral regurgitation., Areas Covered: This review covered relevant publications of M-TEER and summarizes the development of M-TEER devices within the last 15 years. It outlines anatomical challenges which drove the evolution of M-TEER devices, provides an overview about the current state of clinical application and research, and offers an outlook into the future of transcatheter mitral valve treatment., Expert Opinion: The development and refinement of new M-TEER device generations offer the possibility to treat a wide range of mitral valve anatomies. Choosing the best device for the individual anatomic properties of the patients and considering comorbidities is the key to maximized MR reduction, minimalized complication rates, and thus optimized postinterventional prognosis. Independent from prognostic implications, quality of life has become an important patient-centered outcome that can be improved by M-TEER in virtually all patients treated.

Mitral regurgitation (MR) is the most prevalent valvular heart disease and, when left untreated, results in reduced quality of life, heart failure, and increased mortality. Mitral valve transcatheter edge-to-edge repair (M-TEER) has matured considerably as a non-surgical treatment option since its commercial introduction in Europe in 2008. As a result of major device and interventional improvements, as well as the accumulation of experience by the interventional cardiologists, M-TEER has emerged as an important therapeutic strategy for patients with severe and symptomatic MR in the current European and American guidelines. Herein, we provide a comprehensive up-do-date overview of M-TEER. We define preprocedural patient evaluation and highlight key aspects for decision-making. We describe the currently available M-TEER systems and summarise the evidence for M-TEER in both primary mitral regurgitation (PMR) and secondary mitral regurgitation (SMR). In addition, we provide recommendations for device selection, intraprocedural imaging and guiding, M-TEER optimisation and management of recurrent MR. Finally, we provide information on major unsolved questions and "grey areas" in M-TEER.

Background: Secondary mitral regurgitation (SMR) is a progressive disease with characteristic pathophysiological changes that may influence prognosis. Although the staging of SMR patients suffering from heart failure with reduced ejection fraction (HFrEF) according to extramitral cardiac involvement has prognostic value in medically treated patients, such data are so far lacking for edge-to-edge mitral valve repair (M-TEER)., Objectives: This study sought to classify M-TEER patients into disease stages based on the phenotype of extramitral cardiac involvement and to assess its impact on symptomatic and survival outcomes., Methods: Based on echocardiographic and clinical assessment, patients were assigned to 1 of the following HFrEF-SMR groups: left ventricular involvement (Stage 1), left atrial involvement (Stage 2), right ventricular volume/pressure overload (Stage 3), or biventricular failure (Stage 4). A Cox regression model was implemented to investigate the impact of HFrEF-SMR stages on 2-year all-cause mortality. The symptomatic outcome was assessed with New York Heart Association functional class at follow-up., Results: Among a total of 849 eligible patients who underwent M-TEER for relevant SMR from 2008 until 2019, 9.5% (n = 81) presented with left ventricular involvement, 46% (n = 393) with left atrial involvement, 15% (n = 129) with right ventricular pressure/volume overload, and 29% (n = 246) with biventricular failure. An increase in HFrEF-SMR stage was associated with increased 2-year all-cause mortality after M-TEER (HR: 1.39; CI: 1.23-1.58; P < 0.01). Furthermore, higher HFrEF-SMR stages were associated with significantly less symptomatic improvement at follow-up., Conclusions: The classification of M-TEER patients into HFrEF-SMR stages according to extramitral cardiac involvement provides prognostic value in terms of postinterventional survival and symptomatic improvement., Competing Interests: Funding Support and Author Disclosures Dr Orban has received speaker fees from Abbott Vascular and Tomtec Imaging Systems. Dr Karam has received consultant fees from Edwards Lifesciences and Medtronic; and has received proctor fees from Abbott. Dr von Bardeleben has received institutional grants and has served as a speaker for Abbott Vascular and Edwards Lifesciences; and has performed trials unpaid for Abbott Vascular, Edwards Lifesciences, Lifetec, Medtronic, and NeoChord. Dr Iliadis has received travel support from Abbott; and has received consultant honoraria from Abbott and Edwards Lifesciences. Dr Pfister has received consultancy and speaker fee from Edwards Lifesciences; and has received speaker fee by Abbott Vascular. The Department of Cardiology of the Leiden University Medical Centre received unrestricted research grants from Abbott Vascular, Bayer, Biotronik, Bioventrix, Boston Scientific, Edwards Lifesciences, GE Healthcare, and Medtronic. Dr Higuchi has received lecture fees from Medtronic Japan, Daiichi Sankyo, and Ono Pharmaceutical Company. Dr Petronio has received consulting fees and honoraria for lectures from Abbott and Medtronic; has received consulting fees from Boston; and has received honoraria fees from Daiichi Sankyo. Dr Melica has served as a proctor for Abbott Vascular. Dr Braun has received speaker honoraria from Abbott Vascular. Dr Windecker reports research and educational grants to the institution from Abbott, Abiomed, Amgen, AstraZeneca, Bayer, Biotronik, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb, Cardinal Health, CardioValve, Corflow Therapeutics, CSL Behring, Daiichi Sankyo, Edwards Lifesciences, Guerbet, InfraRedx, Janssen-Cilag, Johnson and Johnson, Medicure, Medtronic, Merck Sharp and Dohm, Miracor Medical, Novartis, Novo Nordisk, Organon, OrPha Suisse, Pfizer, Polares, Regeneron, Sanofi-Aventis, Servier, Sinomed, Terumo, Vifor, and V-Wave. Dr Windecker serves as an unpaid advisory board member and/or unpaid member of the steering/executive group of trials funded by Abbott, Abiomed, Amgen, AstraZeneca, Bayer, Boston Scientific, Biotronik, Bristol Myers Squibb, Edwards Lifesciences, Janssen, MedAlliance, Medtronic, Novartis, Polares, Recardio, Sinomed, Terumo, V-Wave, and Xeltis but has not received personal payments by pharmaceutical companies or device manufacturers. Dr Windecker is also member of the steering/executive committee group of several investigator-initiated trials that receive funding by industry without impact on his personal remuneration. Dr Praz has received travel expenses from Abbott Vascular, Polares Medical, and Edwards Lifesiences. Dr Kalbacher has received proctor and lecture fees from Edwards Lifesciences; and has received lecture fees from Abbott Vascular. Dr Lurz has received grants from Abbott Medical and Edwards Lifesciences. Dr Bax has received speaker fees from Abbott Vascular and Edwards Lifesciences. Dr Hausleiter has received research support and speaker honoraria from Edwards Lifesciences. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Aims: Right ventricular dysfunction (RVD), as expressed by right ventricular to pulmonary artery coupling, has recently been identified as a strong outcome predictor in patients undergoing mitral valve edge-to-edge repair (M-TEER) for secondary mitral regurgitation (MR). The aim of this study was to define RVD in patients undergoing M-TEER for primary MR (PMR) and to evaluate its impact on procedural MR reduction, symptomatic development and 2-year all-cause mortality., Methods and Results: This multicentre study included patients undergoing M-TEER for symptomatic PMR at nine international centres. The study cohort was divided into a derivation (DC) and validation cohort (VC) for calculation and validation of the best discriminatory value for RVD. A total of 648 PMR patients were included in the study. DC and VC were comparable regarding procedural success and outcomes at follow-up. Sensitivity analysis identified RVD as an independent predictor for 2-year mortality in the DC (hazard ratio [HR] 2.37, 95% confidence interval [CI] 1.47-3.81, p < 0.001), which was confirmed in the VC (HR 2.06, 95% CI 1.36-3.13, p < 0.001). Procedural success (MR ≤2+) and symptomatic improvement at follow-up (New York Heart Association [NYHA] class ≤II) were lower in PMR patients with RVD (MR ≤2+: 82% vs. 93%, p = 0.002; NYHA class ≤II: 57.3% vs. 66.5%, p = 0.09 for with vs. without RVD). In all PMR patients, the presence of RVD significantly impaired 2-year survival after M-TEER (HR 2.23, 95% CI 1.63-3.05, p < 0.001)., Conclusions: Mitral valve edge-to-edge repair is an effective treatment option for PMR patients. The presence of RVD is associated with less MR reduction, less symptomatic improvement and increased 2-year mortality. Accordingly, RVD might be included into pre-procedural prognostic considerations., (© 2022 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Cardiac arrest still accounts for a substantial proportion of cardiovascular related deaths and is associated with a tremendous risk of neurological injury and, among the few survivors, poor quality of life. Critical determinants of survival and long-term functional status after cardiac arrest are timely initiation of cardiopulmonary resuscitation and use of an external defibrillator for patients with a shockable rhythm. Outcomes are still far from satisfactory, despite ongoing efforts to improve cardiac arrest response systems, as well as elaborate postresuscitation algorithms. Targeted temperature management at the wide range between 32 °C and 36 °C has been one of the main therapeutic strategies to improve neurological outcome in postresuscitation care. This recommendation has been mainly based on 2 small randomized trials that were published 20 years ago. Most recent data derived from the TTM2 (Targeted Hypothermia Versus Targeted Normothermia After Out-of-Hospital Cardiac Arrest) trial, which included 1861 patients, challenge this strategy. It showed no benefit of targeted hypothermia at 33 °C over normothermia at 36 °C to 37.5 °C with fever prevention. Because temperature management at lower temperatures also correlated with an increased risk of side effects without any benefit in the TTM2 trial, a modification of the guidelines with harmonizing temperature management to normothermia might be necessary.

Since transcatheter edge-to-edge repair (TEER) has become a valuable therapy in the treatment of both, mitral (MR) and tricuspid regurgitation (TR), the question of optimized patient selection has gained growing importance. After years of attributing rather little attention to the right ventricle (RV) and its function in the setting of valvular heart failure, this neglect has recently changed. The present review sought to summarize anatomy and function of the RV in a clinical context and aimed at presenting the current knowledge on how the RV influences outcomes after TEER for atrioventricular regurgitation. The anatomy of the RV is determined by its unique shape, which necessitates to use three-dimensional imaging methods for detailed and comprehensive characterization. Complex parameters such as RV to pulmonary artery coupling (RVPAc) have been developed to combine information of RV function and afterload which is primary determined by the pulmonary vasculature and LV filling pressure. Beyond that, TR, which is closely related to RV function also plays an important role in the setting of TEER. While mitral valve transcatheter edge-to-edge repair (M-TEER) leads to reduction of concomitant TR in some patients, the prognostic value of TR in the setting of M-TEER remains unclear. Overall, this review summarizes the current state of knowledge of the outstanding role of RV function and associated TR in the setting of TEER and outlines the unsolved questions associated with right-sided heart failure., Competing Interests: Author MatO has received speaker fees from Tomtec Imaging System. Authors DB and MN were received speaker honoraria from Abbott Vascular. Author MarO has received speaker honoraria from Abbott Medical, AstraZeneca, Abiomed, Bayer vital, BIOTRONIK, Bristol Myers Squibb, CytoSorbents, Daiichi Sankyo Deutschland, Edwards Lifesciences Services, and Sedana Medical. Author JH has received speaker honoraria from and serves as consultant for Edwards Lifesciences. 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., (Copyright © 2022 Stolz, Doldi, Weckbach, Stocker, Braun, Orban, Wild, Hagl, Massberg, Näbauer, Hausleiter and Orban.)

Background: Percutaneous coronary intervention (PCI) is indispensable in cardiology; however, exposure to potentially harmful ionising radiation remains a concern., Aims: This study was designed to assess the PCI-related radiation dose over the last decade and to identify predictors of increased dose exposure., Methods: The PROcedural radiaTion dose Exposure in percutaneous Coronary intervenTION (PROTECTION VIII) study included all PCIs reported to a German quality assurance programme between 2008 and 2018. Dose area product (DAP) and radiation time were analysed. Effective dose (ED) was estimated (ED=DAP*k; conversion coefficient k=0.0022 mSv/cGy*cm 2 ). Multivariate linear regression analysis was used to identify predictors associated with a clinically relevant increase of radiation dose (ED ≥1 mSv)., Results: We enrolled 3,704,986 patients undergoing PCI (median age 70 years, 30% female). Indications were chronic coronary syndrome (37.5%), unstable angina pectoris and non-ST-segment elevation myocardial infarction (non-STEMI; 33.2%) and STEMI (18.5%). Median DAP was 4,203 (interquartile range [IQR] 2,313-7,300) cGy*cm, ED was 9.2 mSv and median radiation time was 9.2 (IQR 5.8-15.0) min. Within the 10-year period, radiation exposure was reduced by 36% (p<0.001) and resulted in a median DAP of 3,070 cGy*cm (ED 6.8 mSv) in 2018. A significant 5.3-fold variability of median DAP was observed between catheterisation laboratories (p<0.001). We identified patient-related (gender, coronary artery bypass graft surgery, heart failure) and procedure-related (coronary occlusion PCI, ostial lesion PCI, left main PCI, multivessel PCI) predictors of increased radiation dose (all p<0.001)., Conclusions: This radiation dose survey demonstrates a considerable reduction of PCI radiation exposure during the last decade. However, large variability between catheterisation laboratories underlines the need for further radiation dose reduction.

Aims: Tricuspid regurgitation (TR) is associated with high mortality, morbidity and reduced physical capacity. This study was designed to examine the long-term impact of transcatheter tricuspid valve intervention (TTVI) on physical activity by using the method of actigraphy., Methods and Results: Overall, we prospectively included 128 heart failure patients with severe TR (median age 79 years, 48% female) who were scheduled for TTVI. Patients were equipped with activity tracking devices for 1 week before TTVI, and again at 1-6 months and 1 year after TTVI. We compared continuous physical activity (CPA), defined as the mean number of steps/day with New York Heart Association class, quality of life assessments, and 6-min walk distance (all p <0.01). TTVI reduced TR to grade ≤2+ in 94% of patients. Median (interquartile range [IQR]) CPA at baseline was 3108 (1350-4959) steps/day, which increased by 31.4% to 3958 (1823-5657) steps/day at 1-6 months and 4080 (2293-6514) steps/day at 1 year after TTVI (p <0.001 for both comparisons). The impact of TTVI was significantly higher in advanced heart failure patients with low baseline activity (baseline CPA <1350 steps/day; 1-year CPA increase: +121.3%; p <0.001), when compared to moderate activity patients (baseline CPA 1350-4959 steps/day; 1-year CPA increase: +27.5%; p <0.01) or high activity patients (baseline CPA >4959 steps/day; 1-year CPA change: +2.6%; p = 0.39)., Conclusion: One-week actigraphy demonstrates durable improvement of physical activity after TTVI. Fragile chronic heart failure patients with very low baseline activity, as determined by actigraphy in this study, significantly benefit from transcatheter intervention and should not be excluded from TTVI., (© 2022 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

(1) Herpes simplex virus (HSV) reactivation in critically ill patients can cause infection in the lower respiratory tract, prolonging mechanical ventilation. However, the association of HSV reactivation with cardiogenic shock (CS) is unclear. As CS is often accompanied by pulmonary congestion and reduced immune system activity, the aim of our study was to determine the incidence and outcome of HSV reactivation in these patients. (2) In this retrospective, single-center study, bronchial lavage (BL) was performed on 181 out of 837 CS patients with mechanical ventilation. (3) In 44 of those patients, HSV was detected with a median time interval of 11 days since intubation. The occurrence of HSV was associated with an increase in C-reactive protein and the fraction of inspired oxygen at the time of HSV detection. Arterial hypertension, bilirubin on ICU admission, the duration of mechanical ventilation and out-of-hospital cardiac arrest were associated with HSV reactivation. (4) HSV reactivation could be detected in 24.3% of patients with CS on whom BL was performed, and its occurrence should be considered in patients with prolonged mechanical ventilation. Due to the limited current evidence, the initiation of treatment for these patients remains an individual choice. Dedicated randomized studies are necessary to investigate the efficacy of antiviral therapy.

Background: The impact of devices for vessel closure on the safety and efficacy of cannula removal in VA-ECMO patients is unknown., Methods: We retrospectively analyzed 180 consecutive patients weaned from VA-ECMO after cardiac arrest or cardiogenic shock from January 2012 to June 2020. In the first period (historical technique group), from January 2012 to December 2018, primary decannulation strategy was manual compression. In the second period (current technique group), from January 2019 to June 2020, decannulation was performed either by a conventional approach with manual compression or by a suture-mediated closure device technique., Results: A femoral compression system was necessary in 71% of patients in the historical group compared to 39% in the current technique group ( p  < 0.01). Vascular surgery was performed in 12% in the historical cohort and 2% in the current technique cohort, which indicated a clear trend, albeit it did not reach significance ( p  = 0.07)., Conclusion: We illustrated that a suture-mediated closure device technique for VA-ECMO decannulation was feasible, safe, and may have reduced the need of surgical interventions compared to manual compression alone., Competing Interests: Christopher Stremmel and Clemens Scherer received speaker honoraria from AstraZeneca, outside the submitted work. Daniel Braun received speaker honoraria from Abbott Vascular, outside the submitted work. Jörg Hausleiter received speaker honoraria and research support from Abbott Vascular and Edwards Lifesciences, outside the submitted work. Martin Orban received speaker honoraria from Abbott Medical, AstraZeneca, Abiomed, Bayer Vital, BIOTRONIK, Bristol-Myers Squibb, CytoSorbents, Daiichi Sankyo Deutschland, Edwards Lifesciences Services, and Sedana Medical, outside the submitted work. The other authors declare that they have no conflicts of interest., (Copyright © 2022 Clemens Scherer et al.)

Despite the rapid increase in experience and technological improvement, the incidence of conduction disturbances in patients undergoing transcatheter aortic valve replacement (TAVR) with the self-expandable CoreValve Evolut valve remains high. Recently, a cusp-overlap view (COP) implantation technique has been proposed for TAVR with self-expandable valves offering an improved visualization during valve expansion compared to the three-cusp view (TCV). This study aims to systematically analyze procedural outcomes of TAVR patients treated with the CoreValve Evolut valve using a COP compared to TCV in a high-volume center. The primary endpoint was technical success according the 2021 VARC-3 criteria. A total of 122 consecutive patients (61 pts. TCV: April 2019 to November 2020; 61 pts. COP: December 2020 to October 2021) that underwent TAVR with the CoreValve Evolut prosthesis were included in this analysis. Although there was no difference in the primary endpoint technical success between TCV and COP patients (93.4% vs. 90.2%, OR 0.65, 95% CI 0.16, 2.4, p = 0.51), we observed a significantly lower risk for permanent pacemaker implantation (PPI) among COP patients (TCV: 27.9% vs. COP: 13.1%, OR 0.39, 95% CI 0.15, 0.97, p = 0.047). Implantation of the CoreValve Evolut prosthesis using the COP might help to reduce the rate of PPI following TAVR.

Aims: Automated coronary total plaque volume (TPV) quantification derived from coronary computed tomographic angiography (CTA) datasets provide exact and reliable assessment of calcified and non-calcified coronary atherosclerosis burden. The aim of this analysis was to investigate the long-term predictive value of TPV., Methods and Results: TPV was quantified in 1577 patients undergoing coronary CTA and cardiovascular events were collected during 10.5 years (interquartile range 6.0-11.4) of follow-up. The study endpoint comprised cardiac death and acute coronary syndrome and occurred in 59 (3.7%) patients. Coronary TPV provided additive prognostic value over clinical risk assessed with the Morise Score and coronary artery disease severity (rise in C-index from 0.744 to 0.769, P = 0.03). A category-based reclassification approach combining the Morise Score and TPV revealed superior risk stratification (categorical net reclassification improvement: 0.48 with 95% CI 0.13-0.68, P < 0.001) and resulted in reclassification of 800 (51%) patients compared with the Morise Score alone. The 10-year risk for the study endpoint was 0.6% (95% CI 0-1.3) for patients classified as low risk (n = 807), 4.8% (95% CI 2.4-7.2) for patients at intermediate risk (n = 400), and 10.3% (95% CI 6.6-13.9) for patients at high risk (n = 370) using the combined reclassification approach., Conclusion: Quantification of TPV from coronary CTA permits an improved 10-year cardiovascular risk stratification., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)

Objectives: This study was designed to assess hemodynamic changes in response to transcatheter tricuspid valve edge-to-edge repair (TTVR) and to identify hemodynamic predictors associated with mortality., Background: Severe tricuspid regurgitation (TR) is associated with high mortality. TTVR effectively alleviates heart failure symptoms, but comprehensive hemodynamic characterization of patients undergoing TTVR is currently lacking., Methods: This international, multicenter study included 236 patients undergoing TTVR. Data from clinical assessment, echocardiography, intraprocedural right heart catheterization, and noninvasive cardiac output measurement were analyzed. Hemodynamic predictors for mortality were identified using linear Cox regression analysis and were used for stratification of patients with subsequent analysis of survival time., Results: Patients (median age 78 years, 53% women) were symptomatic (89% in New York Heart Association functional class III or IV) because of severe TR (grade ≥3+ in 100%). TTVR significantly reduced TR at discharge (grade ≥3+ in 16%; p < 0.001), with a corresponding 19% reduction of the right atrial v wave (21 mm Hg vs. 16 mm Hg; p < 0.001) and an improvement in cardiac output (from 3.5 to 4.0 l/min; p < 0.01). Invasive mean pulmonary artery pressure, transpulmonary gradient, pulmonary vascular resistance, and right ventricular stroke work were significant predictors of 1-year mortality (p < 0.05 for all). Hemodynamic stratification by mean pulmonary artery pressure and transpulmonary gradient best predicted 1-year survival (p < 0.001). Although patients with pre-capillary dominant pulmonary hypertension showed an unfavorable prognosis (1-year survival 38%), patients without or with post-capillary pulmonary hypertension had favorable outcome (1-year survival 92% or 78%, respectively)., Conclusions: Invasive assessment of cardiopulmonary hemodynamic status predicts survival after TTVR. Invasive hemodynamic characterization may help identify patients profiting most from TTVR., Competing Interests: Author Disclosures Dr. Braun has received speaker honoraria from Abbott Vascular. Dr. Fam is a consultant for Edwards Lifesciences; and has received speaker honoraria from Abbott Vascular. Dr. von Bardeleben has received speaker honoraria from Abbott Vascular and Edwards Lifesciences. Dr. Lurz has received research grants from Edwards Lifesciences and Abbott Vascular; and is a consultant to Edwards Lifesciences and Abbott Vascular. Dr. Hausleiter has received speaker honoraria and research support from and serves as a consultant for Abbott Vascular and Edwards Lifesciences. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021. Published by Elsevier Inc.)

The number of patients treated with the mechanical circulatory support device Impella Cardiac Power (CP) for cardiogenic shock is steadily increasing. The aim of this study was to investigate long-term survival and complications related to this modality. Patients undergoing Impella CP treatment for cardiogenic shock were retrospectively enrolled and matched with cardiogenic shock patients not treated with mechanical circulatory support between 2010 and 2020. Data were collected from the cardiogenic shock registry of the university hospital of Munich (DRKS00015860). 70 patients with refractory cardiogenic shock without mechanical circulatory support were matched with 70 patients treated with Impella CP. At presentation, the mean age was 67 ± 15 years with 80% being male in the group without support and 67 ± 14 years ( p = 0.97) with 76% being male ( p = 0.68) in the group with Impella. There was no significant difference in the rate of cardiac arrest (47% vs. 51%, p = 0.73) and myocardial infarction was the predominant cause of cardiogenic shock in both groups (70% vs. 77%). A total of 41% of patients without cardiocirculatory support and 54% of patients with Impella support died during the first month ( p = 0.17). After one year, mortality rates were similar in both groups (55% in conventional vs. 59% in Impella CP group, p = 0.30) as was mortality rate at long-term 5-years follow-up (64% in conventional vs. 73% in Impella CP group, p = 0.33). The rate of clinically significant bleedings during ICU stay was lower in the conventional group than in the Impella support group (15% vs. 43%, p = 0.002). In this small observational and non-randomized analysis no difference in long-term outcome between patients treated with Impella CP vs. guideline directed cardiogenic shock therapy without mechanical circulatory support could be detected. Care must be taken regarding the high rate of bleeding and vascular complications when using Impella CP. Large, adequately powered studies are urgently needed to investigate the efficacy and safety of Impella CP in cardiogenic shock.

The feasibility and hemodynamic effects of isoflurane sedation in cardiogenic shock in the presence of venoarterial extracorporeal membrane oxygenation treatment are currently unknown., Design: Retrospective single-center study., Setting: Cardiac ICU of Munich university hospital., Patients/subjects: Cardiogenic shock patients with venoarterial extracorporeal membrane oxygenation treatment under sedation with volatile isoflurane between November 2018 and October 2019 have been enrolled in this study and were matched by propensity score in a 1:1 ratio with IV sedated patients treated between January 2013 and November 2018 from the cardiogenic shock registry of the university hospital of Munich., Measurements and Main Results: Isoflurane sedation was used in 32 patients with cardiogenic shock and venoarterial extracorporeal membrane oxygenation treatment. The mean age of conventionally sedated patients was 58.4 ± 13.8 years and 56.3 ± 11.5 years for patients with isoflurane sedation ( p = 0.51). Administration of isoflurane was associated with lower IV sedative drug use during venoarterial extracorporeal membrane oxygenation treatment (86% vs 32%; p = 0.01). Mean systolic arterial pressure was similar (94.3 ± 12.6 vs 92.9 ± 10.5 mm Hg; p = 0.65), but mean heart rate was significantly higher in the conventional sedation group, when compared with the isoflurane group (85.2 ± 20.5 vs 74.7 ± 15.0 beats/min; p = 0.02). Catecholamine doses, venoarterial extracorporeal membrane oxygenation blood and gas flow, ventilation time (304 ± 143 vs 398 ± 272 hr; p = 0.16), bleeding complications bleeding academic research consortium 3a or higher (59.3% vs 65.3%; p = 0.76), and 30-day mortality (59.2% vs 63.4%, p = 0.80) were similar in both groups. The overall sedation costs per patient were significantly lower in the conventional group, when compared with the isoflurane group (537 ± 624 vs 1280 ± 837 €; p < 0.001)., Conclusions: Volatile sedation with isoflurane is feasible-albeit at higher costs-in patients with cardiogenic shock and venoarterial extracorporeal membrane oxygenation treatment and was not associated with higher catecholamine dosage or extracorporeal membrane oxygenation flow rate compared with IV sedation., Competing Interests: Dr. Orban received speaker honoraria from SedanaMedical and AstraZeneca, outside the submitted work; he received personal fees from Edward Life Sciences, outside the submitted work. Dr. Hausleiter received speaker honoraria and research support from Abbott Vascular and Edwards Lifesciences, outside the submitted work. The remaining authors declare no conflict of interests., (Copyright © 2020 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.)

Rationale: A reduced rate of myocardial infarction has been reported in patients with atrial fibrillation treated with FXa (factor Xa) inhibitors including rivaroxaban compared with vitamin K antagonists. At the same time, low-dose rivaroxaban has been shown to reduce mortality and atherothrombotic events in patients with coronary artery disease. Yet, the mechanisms underlying this reduction remain unknown., Objective: In this study, we hypothesized that rivaroxaban's antithrombotic potential is linked to a hitherto unknown rivaroxaban effect that impacts on platelet reactivity and arterial thrombosis., Methods and Results: In this study, we identified FXa as potent, direct agonist of the PAR-1 (protease-activated receptor 1), leading to platelet activation and thrombus formation, which can be inhibited by rivaroxaban. We found that rivaroxaban reduced arterial thrombus stability in a mouse model of arterial thrombosis using intravital microscopy. For in vitro studies, atrial fibrillation patients on permanent rivaroxaban treatment for stroke prevention, respective controls, and patients with new-onset atrial fibrillation before and after first intake of rivaroxaban (time series analysis) were recruited. Platelet aggregation responses, as well as thrombus formation under arterial flow conditions on collagen and atherosclerotic plaque material, were attenuated by rivaroxaban. We show that rivaroxaban's antiplatelet effect is plasma dependent but independent of thrombin and rivaroxaban's anticoagulatory capacity., Conclusions: Here, we identified FXa as potent platelet agonist that acts through PAR-1. Therefore, rivaroxaban exerts an antiplatelet effect that together with its well-known potent anticoagulatory capacity might lead to reduced frequency of atherothrombotic events and improved outcome in patients.

Introduction : Secondary mitral regurgitation (MR) is a consequence of chronic heart failure (HF) with reduced left ventricular ejection fraction (HFrEF) and left ventricular (LV) dilatation. Severe MR worsens prognosis and accelerates LV dilatation as well as decline in LV ejection fraction. Areas covered : In this review we summarize the available data of patients with chronic HF undergoing transcatheter edge-to-edge mitral valve repair (TMVR) with the MitraClip system for severe secondary MR, considering also results of recent MITRA-FR (Multicenter Study of Percutaneous Mitral Valve Repair MitraClip Device in Patients With Severe Secondary Mitral Regurgitation) and COAPT (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation) trials. Furthermore, we discuss recent advances in devices for TMVR, focussing on the new MitraClip XTR as well as the Edwards PASCAL system. Expert opinion : Optimal patient selection for TMVR is still a matter of great debate due to contradictory results of MITRA-FR and COAPT. New edge-to-edge devices (MitraClip XTR and Edwards PASCAL) come with longer clip arms and the Edwards PASCAL system is the first device with the capability of independent grasping of anterior and posterior leaflet, providing interventionalists with more options to treat patients with secondary MR.

Objectives: The aim of this study was to assess the use of low tube potentials for coronary computed tomography angiography (CCTA) in worldwide clinical practice and its influence on radiation exposure, contrast agent volume, and image quality., Background: CCTA is frequently used in clinical practice. Lowering of tube potential is a potent method to reduce radiation exposure and to economize contrast agent volume., Methods: CCTAs of 4,006 patients from 61 international study sites were analyzed regarding very-low (≤80 kVp), low (90 to 100 kVp), conventional (110 to 120 kVp), and high (≥130 kVp) tube potentials. The impact on dose-length product (DLP) and contrast agent volume was analyzed. Image quality was determined by evaluation of the diagnostic applicability and assessment of the objective image parameters signal-to-noise-ratio (SNR) and contrast-to-noise-ratio (CNR)., Results: When compared with conventional tube potentials, low tube potentials were used in 56% of CCTAs (≤80 kVp: 9%; 90 to 100 kVp: 47%), which varied among sites from 0% to 100%. Tube potential reduction was associated with low-cardiovascular risk profile, low body mass index (BMI), and new-generation scanners. Median radiation exposure was lowered by 68% or 50% and median contrast agent volume by 25% or 13% for tube potential protocols of ≤80 kVp or 90 to 100 kVp when compared with conventional tube potentials, respectively (all p < 0.001). With the use of lower tube potentials, the frequency of diagnostic scans was maintained (p = 0.41), whereas SNR and CNR significantly improved (both p < 0.001). Considering BMI eligibility criteria, 58% (n = 946) of conventionally scanned patients would have been suitable for low tube potential protocols, and 44% (n = 831) of patients scanned with 90 to 100 kVp would have been eligible for very-low tube potential CCTA imaging of ≤80 kVp., Conclusions: This large international registry confirms the feasibility of tube potential reduction in clinical practice leading to lower radiation exposure and lower contrast volumes. The current registry also demonstrates that this strategy is still underused in daily practice. (PROspective multicenter registry on radiaTion dose Estimates of cardiac CT angIOgraphy iN daily practice in 2017 [PROTECTION-VI]; NCT02996903)., (Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Clinical observations implicate a role of eosinophils in cardiovascular diseases because markers of eosinophil activation are elevated in atherosclerosis and thrombosis. However, their contribution to atherosclerotic plaque formation and arterial thrombosis remains unclear. In these settings, we investigated how eosinophils are recruited and activated through an interplay with platelets. Here, we provide evidence for a central importance of eosinophil-platelet interactions in atherosclerosis and thrombosis. We show that eosinophils support atherosclerotic plaque formation involving enhanced von Willebrand factor exposure on endothelial cells and augmented platelet adhesion. During arterial thrombosis, eosinophils are quickly recruited in an integrin-dependent manner and engage in interactions with platelets leading to eosinophil activation as we show by intravital calcium imaging. These direct interactions induce the formation of eosinophil extracellular traps (EETs), which are present in human thrombi and constitute a substantial part of extracellular traps in murine thrombi. EETs are decorated with the granule protein major basic protein, which causes platelet activation by eosinophils. Consequently, targeting of EETs diminished thrombus formation in vivo, which identifies this approach as a novel antithrombotic concept. Finally, in our clinical analysis of coronary artery thrombi, we identified female patients with stent thrombosis as the population that might derive the greatest benefit from an eosinophil-inhibiting strategy. In summary, eosinophils contribute to atherosclerotic plaque formation and thrombosis through an interplay with platelets, resulting in mutual activation. Therefore, eosinophils are a promising new target in the prevention and therapy of atherosclerosis and thrombosis., (© 2019 by The American Society of Hematology.)

Percutaneous dilatational tracheotomy has become a routine procedure in ICUs. However, given the high and steadily growing number of patients receiving anticoagulation, dual antiplatelet therapy, or even a combination of both (also known as "triple therapy"), there are concerns about the safety of the procedure, in particular for critically ill patients with a high risk of bleeding. In this retrospective study, we investigated whether percutaneous dilatational tracheotomy in this high-risk population was associated with elevated procedural complications., Design: Retrospective single-center study with analysis of all percutaneous dilatational tracheotomies performed in our cardiac ICU from January 2018 to May 2019., Setting: Munich university hospital's cardiac ICU., Patients and Interventions: A total of 34 patients who underwent percutaneous dilatational tracheotomy according to Ciaglia technique with accompanying bronchoscopy in our cardiac ICU from January 2018 to May 2019 were included. Patients were stratified into clinically relevant risk groups based on anticoagulation and antiplatelet therapy considering standard laboratory coagulation parameters, that is, activated partial thromboplastin time, international normalized ratio, and platelet count with differentiated analysis of procedure-related complications in each risk group until hospital discharge., Measurements and Main Results: A total of 34 patients who underwent percutaneous dilatational tracheotomy were included and assigned to five clinically relevant treatment groups: IV unfractionated heparin (prophylactic dosage) ( n = 4), IV unfractionated heparin (therapeutic dosage) ( n = 4), aspirin and IV unfractionated heparin (therapeutic dosage) ( n = 7), dual antiplatelet therapy with IV unfractionated heparin (prophylactic dosage) ( n = 5), and dual antiplatelet therapy with IV unfractionated heparin (therapeutic dosage) ( n = 14). Three bleedings without surgical intervention or blood transfusion were documented in the whole cohort, but no single bleeding did occur in the triple therapy group. These were exclusively caused by skin bleedings at the immediate puncture site-each of which could be easily treated with one or two single stitches. There were no severe bleeding complications or potentially life-threatening procedure-related complications. Additionally, the rate of complications in patients with elevated body mass index was not increased., Conclusions: Bronchoscopy-guided percutaneous dilatational tracheotomy according to Ciaglia technique with careful consideration of all potential indications and contraindications may be a safe and low-complication procedure for airway management, even in patients receiving dual antiplatelet therapy and therapeutic anticoagulation simultaneously in our cohort with a high risk of bleeding., Competing Interests: The authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2019 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.)

Objectives: This study sought to determine the impact of transcatheter tricuspid edge-to-edge valve repair (TTVR) of severe tricuspid regurgitation (TR) on kidney and liver functions., Background: TR leads to impairment in renal and hepatic function, which is associated with worse prognosis. TTVR emerged as a treatment option for patients ineligible for cardiac surgery. However, no study has assessed the impact of TTVR on kidney and liver functions., Methods: All patients treated with TTVR in our center between March 2016 and June 2018 were included. Kidney and liver functions were compared at baseline, 30 days, and 6 months., Results: Over the study period, 126 patients were treated for TR (59 isolated TTVR and 67 TMTVR). Among them, 110 (87.3%) survived at 6 months. Among survivors, renal function remained stable, including among patients with moderate-to-severe chronic kidney disease (mean glomerular filtration rate 37.5 ml/min/1.73 m 2 at baseline vs. 40.1 ml/min/1.73 m 2 at 6 months; p = 0.39). Regarding liver function, a significant improvement at 6 months was only observed in the alanine transaminase level in the entire cohort (30.7 U/l vs. 24.9 U/l; p < 0.001). Among patients with abnormal baseline liver function, significant reductions in aspartate transaminase (50.5 U/l to 39.9 U/l; p = 0.02) and bilirubin (1.8 mg/dl to 1.5 mg/dl; p = 0.03) were also observed., Conclusions: TR reduction by TTVR is associated with an improvement in liver function, mainly among patients with abnormal liver function at baseline, whereas kidney function remained stable. Accordingly, TTVR is an attractive option especially for patients presenting with severe TR and liver dysfunctions, who are at even higher surgical risk compared with patients who still have normal organ functions., (Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Aims: Advances of cardiac computed tomography angiography (CTA) have been developed for dose reduction, but their efficacy in clinical practice is largely unknown. This study was designed to evaluate radiation dose exposure and utilization of dose-saving strategies for contrast-enhanced cardiac CTA in daily practice., Methods and Results: Sixty one hospitals from 32 countries prospectively enrolled 4502 patients undergoing cardiac CTA during one calendar month in 2017. Computed tomography angiography scan data and images were analysed in a central core lab and compared with a similar dose survey performed in 2007. Linear regression analysis was performed to identify independent predictors associated with dose. The most frequent indication for cardiac CTA was the evaluation of coronary artery disease in 89% of patients. The median dose-length product (DLP) of coronary CTA was 195 mGy*cm (interquartile range 110-338 mGy*cm). When compared with 2007, the DLP was reduced by 78% (P < 0.001) without an increase in non-diagnostic coronary CTAs (1.7% in 2007 vs. 1.9% in 2017 surveys, P = 0.55). A 37-fold variability in median DLP was observed between the hospitals with lowest and highest DLP (range of median DLP 57-2090 mGy*cm). Independent predictors for radiation dose of coronary CTA were: body weight, heart rate, sinus rhythm, tube voltage, iterative image reconstruction, and the selection of scan protocols., Conclusion: This large international radiation dose survey demonstrates considerable reduction of radiation exposure in coronary CTA during the last decade. However, the large inter-site variability in radiation exposure underlines the need for further site-specific training and adaptation of contemporary cardiac scan protocols.

Background: Wearable cardioverter defibrillator (WCD) therapy is feasible and safe in patients as a transient protection against sudden cardiac death (SCD). However, the impact of WCD therapy on quality of life (QoL) has not been studied., Methods: In our single-centre study, 109 consecutive patients with a prescription of WCD were retrospectively analysed. Quality of life has been assessed by a standardized questionnaire (EQ-5D-3L, modified). Additionally, clinical baseline and follow-up data and recorded arrhythmic episodes were evaluated., Results: Mean WCD therapy time was 56.2 (± 42.4) days, with a daily wear time of 19.7 (± 5) hours. A total of 3441 arrhythmia episodes were detected. Of these, 27 (1%) were adequate but did not require shock therapy. Likewise, no inadequate shock therapy occurred. WCD therapy negatively affected quality of life: 43% of patients reported mental health issues. 37% reported pain or discomfort. Self-care, usual activities, and mobility were restricted in 17%, 48%, and 36%, respectively. 29% were afraid of receiving shock therapy, and 48% suffered from sleep disturbance. However, 64% indicated having felt safe during WCD therapy. Accordingly, average quality of life was rated 70/100 points., Conclusion: In our cohort, no SCD was prevented by WCD therapy. In contrast, in this preliminary study quality of life was reduced. Thus, careful recommendation of WCD therapy for high risk patients should be considered.