Philipp Lurz

Background: Transcatheter tricuspid edge‐to‐edge repair (T‐TEER) has developed as a treatment option for patients experiencing severe tricuspid regurgitation. T‐TEER consistently reduces tricuspid regurgitation, but data on subsequent right heart remodeling remain limited. The aim of this study was to evaluate changes in right heart dimension and function after T‐TEER using extended echocardiographic follow‐up. Methods: The study was based on the international EuroTR (European Registry of Transcatheter Repair for Tricuspid Regurgitation), including patients undergoing T‐TEER between 2016 and 2024 at 18 European centers. Eligible were patients with available baseline and follow‐up (≥90 days postprocedure) echocardiographic assessment. Results: A total of 699 patients (mean age, 78±8 years; 56% women) were included in the analysis. Echocardiographic follow‐up was performed at a median of 407 days (interquartile range, 205–801 days). Right heart dimensions significantly decreased: right ventricular (RV) midventricular diameter from 40.2±8.9 to 37.1±8.4 mm ( P 2 ( P P P <0.001) was observed. Conclusions: In the subset of surviving patients with available echocardiographic follow‐up, treatment with T‐TEER led to favorable long‐term changes with reduced RV dimension, associated with procedural success. RV function modestly decreased, likely reflecting normalization after volume unloading.

BACKGROUND: Studies on mitral transcatheter edge-to-edge repair for atrial functional mitral regurgitation (AFMR) and ventricular functional mitral regurgitation (VFMR) are limited. METHODS: We report 1-year outcomes of mitral transcatheter edge-to-edge repair for AFMR and VFMR using the PASCAL transcatheter valve repair system in the MiCLASP (Transcatheter Repair of Mitral Regurgitation With Edwards Pascal Transcatheter Valve Repair System) multicenter European postmarket clinical follow-up study. RESULTS: Analysis included 295 patients with FMR (75.5±9.93 years old, 59.3% male) from the first 600 enrolled in the MiCLASP study, with AFMR in 17.6% (52) and VFMR in 82.4% (243). Patients with AFMR were older (79.7±6.67 versus 74.6±10.30 years), majority female (75.0% versus 33.3%), and had higher rates of hypertension (98.1% versus 82.3%) and atrial fibrillation (82.7% versus 60.1%) than patients with VFMR (all P P P P =0.661), and patients with AFMR had shorter procedure duration (73.5 versus 85.5 minutes; P =0.044). One-year Kaplan-Meier estimate of freedom from all-cause mortality or heart failure hospitalization was 79.3% in AFMR and 70.9% in VFMR ( P =0.267). Both AFMR and VFMR groups demonstrated significant mitral regurgitation reduction (mitral regurgitation ≤1+, 93.1% and 81.3%), low mean transmitral gradients (3.5 and 3.1 mm Hg), significant proportional reductions in left ventricular end-diastolic volume (−12.9% and −16.4%) and left atrial volume (−9.6% and −10.9%), high proportions at New York Heart Association class I/II (76.5% and 64.6%), and significant increases in Kansas City Cardiomyopathy Questionnaire Overall Summary score (+18.0 and +11.6 points), respectively (all P <0.05 from baseline). CONCLUSIONS: One-year MiCLASP results support the safety of mitral transcatheter edge-to-edge repair with the PASCAL system in both AFMR and VFMR, with comparable echocardiographic, functional, and quality-of-life changes, despite baseline differences in clinical presentation. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT04430075.

Aortic stenosis (AS) is increasingly recognized as a complex myocardial disease rather than an isolated valvular disorder. Emerging translational and clinical evidence suggests that diastolic dysfunction in AS is not merely an epiphenomenon of aging or comorbidity burden but develops early and may represent a central mechanistic link between valvular obstruction and heart failure. Chronic left ventricular pressure overload increases wall stress and myocardial oxygen demand, triggering a cascade of structural, metabolic, and microvascular alterations that culminate in left ventricular hypertrophy, interstitial fibrosis, impaired relaxation, and reduced ventricular compliance. The severity of diastolic dysfunction before aortic valve replacement significantly influences clinical outcomes. Persistent myocardial fibrosis and impaired diastolic reserve may remain despite successful valve intervention, helping explain why a substantial proportion of patients continue to experience heart failure symptoms after valve replacement. Despite its clinical relevance, diastolic dysfunction remains insufficiently integrated into current guideline-directed decision-making, raising the question of whether it should assume a more central role in determining the optimal timing of aortic valve replacement. Beyond correction of valvular obstruction alone, diastolic dysfunction may therefore represent both a marker of advanced myocardial remodeling and a potential therapeutic target in patients with AS.

Background: Transfemoral transcatheter aortic valve implantation (TAVI) is the treatment of choice for severe aortic stenosis in patients with elevated surgical risk. However, vascular complications remain a major source of morbidity and mortality. The protection wire technique was introduced to prevent major access-related complications, but its role in contemporary TAVI practice is uncertain. Aims: To evaluate whether routine protection wire use reduces vascular complications in contemporary transfemoral TAVI. Methods: We performed a retrospective, single-centre analysis of 1476 consecutive patients undergoing transfemoral TAVI between January 2020 and August 2023. Until November 2021, protection wire placement was standard-of-care (Group 1, n = 801); thereafter procedures were performed without routine protection wire use (Group 2, n = 675). Vascular complications were defined according to VARC-3 criteria. Multivariable logistic regression was used to identify independent predictors of minor and major vascular complications. Results: The composite of minor and major vascular complications occurred more frequently in Group 1 than in Group 2 (18.6% vs. 10.8%, p < 0.001). In Group 1, 34.8% of access-related complications were associated with the protection wire access. Major vascular complications were numerically less frequent in Group 2 (2.5% vs. 4.2%). Omission of routine protection wire placement was independently associated with a lower risk (OR 0.52, 95% CI 0.38–0.72, p < 0.001). Conclusion: In contemporary transfemoral TAVI, routine protection wire use was not associated with reduced major vascular complications and was linked to a higher rate of minor access site injuries. These findings support a restrictive rather than routine use of protection wires in current practice.

Background: Functional mitral regurgitation (FMR), resulting from left ventricular dysfunction or left atrial dilation, is associated with heart failure and increased mortality. Mitral transcatheter edge‐to‐edge repair is an established treatment for patients with severe symptomatic FMR who are at high surgical risk. However, comparative data on the 2 most commonly used mitral transcatheter edge‐to‐edge repair systems, MitraClip G4 and PASCAL, remain limited. This study compared the safety and efficacy of both devices in patients with FMR. Methods: Consecutive patients with severe symptomatic FMR who underwent mitral transcatheter edge‐to‐edge repair using MitraClip G4 or PASCAL between 2021 and 2023 at a single center were included. Coprimary end points were 1‐year survival and freedom from heart failure hospitalization. Secondary end points included MR reduction and New York Heart Association functional class. Propensity score matching was performed to adjust for baseline differences. Results: The study included 319 patients, of whom 150 (47.0%) were treated with MitraClip G4 and 169 (53.0%) with PASCAL. After propensity score matching, 116 matched pairs were analyzed. Procedural success, defined as MR grade ≤2, was achieved in 98.1% of the MitraClip G4 group and 97.3% of the PASCAL group ( P =0.61). At 1 year, no significant differences were observed between groups regarding residual MR ( P =0.83), New York Heart Association class ( P =0.41), or freedom from heart failure hospitalization ( P =0.41). Estimated 1‐year survival was 86.7% for MitraClip G4 and 87.8% for PASCAL ( P =0.84). Conclusions: In patients with FMR, MitraClip G4 and PASCAL demonstrated similarly high procedural success, durable MR reduction, and comparable clinical outcomes at 1 year.

BACKGROUND: Endothelial dysfunction is an early event in atherosclerosis development and is centrally linked with insufficient endothelial NO production. However, chronically increased NO levels, including NO from other cellular sources, may induce endothelial dysfunction. Here, we studied how chronically elevated NO production from erythrocytes, achieved by genetic deletion of ARG1 (arginase-1), impacts smooth muscle cell (SMC) lipid accumulation and atherosclerosis progression. METHODS: Primary aortic SMCs from mice lacking ARG1 in red blood cell (RBC.ARG1-knockout [KO]) were subjected to RNA-sequencing, lipidomic, metabolic, and molecular analyses; atherosclerosis burden was quantified en face and at the aortic root. RESULTS: Increased lipid droplet formation in SMCs from RBC.ARG1-KO mice was observed using brightfield and electron microscopy and confirmed by Oil Red O and boron-dipyrromethene lipid dye staining. RNA sequencing revealed the simultaneous overexpression of genes regulating lipid uptake ( Cd36 ), catabolism ( Cpt1a ), and de novo lipogenesis ( Acaca , Fasn [ Fatty acid synthase ]) in RBC.ARG1-KO SMCs, and inhibiting fatty acid translocase (CD36), ACC (acetyl-CoA [coenzyme A] carboxylase), or fatty acid synthase prevented the lipid accumulation in RBC.ARG1-KO SMCs. Increased expression of CD36 downstream of NO and overactivated sGC (soluble guanylyl cyclase)-cyclic guanosine monophosphate signaling was identified as a mediator of increased lipid uptake in RBC.ARG1-KO SMCs. Loss of PDE (phosphodiesterase) 2A, coupling cyclic guanosine monophosphate with cyclic adenosine monophosphate and PKA (protein kinase A) activation, was also observed, resulting in AMPK (5’ AMP-activated protein kinase) inhibition, thus unlocking acetyl-CoA carboxylase, catalyzing the rate-limiting step in fatty acid synthesis. Inhibiting PDE2A recapitulated the RBC.ARG1-KO SMC phenotype, while inhibiting PKA or ATP generation from cyclic adenosine monophosphate abrogated the lipid droplet accumulation in RBC.ARG1-KO SMCs. Increased Oil Red O-positive aortic atherosclerosis burden in hypercholesterolemic apolipoprotein E–deficient RBC.ARG1-KO mice was confirmed by histology and elevated levels of polyunsaturated long-chain cholesterol esters in aortic atheroma by mass spectrometry lipidomics. CONCLUSIONS: Our findings show the importance of erythrocyte-derived NO for metabolically reprogramming SMCs toward increased fatty acid uptake and lipogenesis, and identify PDE2A as a molecular switch linking chronically activated NO signaling with lipid accumulation and atheroma progression.

BACKGROUND: The impact of proportionality to heart valve regurgitation has been widely investigated in mitral regurgitation, helping to better characterize the best candidates for therapies. However, it has never been studied in tricuspid regurgitation (TR). The aim of the present study is to investigate the impact of the proportionality of TR on outcomes. METHODS: Patients undergoing tricuspid transcatheter edge-to-edge repair were selected from the TRIVALVE registry (International Multisite Transcatheter Tricuspid Valve Therapies Registry). Patients were divided according to the ratio between effective regurgitant orifice area (EROA) and right ventricular (RV) end diastolic diameter (RVEDD) into tertiles: patients with low EROA/RVEDD (RV, dominant); intermediate EROA/RVEDD (RV and TR, RV-TR, codominant), and high EROA/RVEDD (TR, dominant). The primary outcome was all-cause mortality. Median follow-up was 9.7 months (4.2–12.0). RESULTS: A total of 204 patients were included in the present study: 67 for the RV dominant, 68 for the RV-TR codominant, and 69 for the TR dominant group. The 3 groups presented different baseline characteristics. Survival analysis among the 3 groups showed a trend towards worse prognosis for the RV-dominant group, as compared with the RV-TR codominant and TR dominant groups. CONCLUSIONS: The conceptual framework of proportionality is applicable to TR with EROA/RVEDD, defining a higher risk RV-dominant phenotype with a trend towards worse survival after tricuspid transcatheter edge-to-edge repair.

Background: Severe tricuspid regurgitation (TR) is associated with high morbidity and mortality. Tricuspid transcatheter edge-to-edge repair (T-TEER) improves TR severity and symptoms, yet survival benefit remains uncertain. This meta-analysis aims to evaluate 1-year outcomes after T-TEER and explore clinical and echocardiographic correlates of prognosis. Methods: A systematic search of PubMed/MEDLINE, Web of Science, and Scopus was conducted through June 2025. Studies enrolling ≥100 patients undergoing T-TEER and reporting 1-year outcomes were included. Primary endpoints were 1-year all-cause mortality, heart failure (HF) hospitalization, and persistence of New York Heart Association (NYHA) class III–IV. Early residual TR (≥3+), assessed at the earliest post-procedural time point within 30 days, was a secondary endpoint. Results: Ten studies, including 4,134 patients, were analyzed. At 1-year, pooled all-cause mortality was 14.0% [95% confidence interval (CI): 9.6–18.5%], HF hospitalization 16.9% (95% CI: 8.7–25.1%), and 30.9% of patients remained in NYHA class III–IV (95% CI: 22.1–39.7%). Early residual TR ≥3+ occurred in 19.1%. In meta-regression analysis, more contemporary recruitment periods were associated with lower 1-year mortality, whereas single-center design was associated with higher early residual TR ≥3+. Exploratory aggregate-level analyses suggested potential associations between comorbidity burden and mortality, right-sided dysfunction and HF hospitalization, and left-sided disease and persistent functional limitation. Conclusions: T-TEER effectively reduces TR and improves functional status; however, 1-year mortality and HF hospitalization remain substantial. More contemporary recruitment periods were associated with lower 1-year all-cause mortality, suggesting improved outcomes over time. Systemic comorbidity burden, right-sided disease, and concomitant left-sided disease may contribute to residual risk after T-TEER; however, these associations should be considered hypothesis-generating and require validation in individual patient-level datasets. Meta-analysis Registration: CRD420251155094.