Two subtypes of atrial functional mitral regurgitation (AFMR) have been described, one is characterized by Carpentier type I and the other by Carpentier type IIIb leaflet motion. The authors sought to analyze echocardiographic characteristics and outcomes of AFMR subtypes undergoing mitral valve transcatheter edge-to-edge repair (M-TEER). Of 1,047 consecutive patients who underwent M-TEER, the authors identified those with isolated mitral annulus dilation (Carpentier I), termed AFMR-IAD, and those with atriogenic hamstringing characterized by restricted posterior mitral leaflet motion (Carpentier IIIb), termed AFMR-AH. Echocardiographic baseline characteristics and outcomes up to 1-year were analyzed. A total of 128 patients (12.2%) met AFMR criteria; 75 (58.6%) were identified as AFMR-IAD and 53 (41.4%) as AFMR-AH. AFMR-AH displayed greater left atrial and left ventricular volumes, greater mitral annulus, shorter and steeper posterior mitral leaflet, and more pronounced MR (all P < 0.05). Technical success was achieved in 98.7% (AFMR-IAD) and 86.8% (AFMR-AH) of patients (P = 0.009). At discharge, device detachments were exclusively observed in AFMR-AH (10.0%). MR ≤II was achieved in 95.6% and 78.6% at 30 days (P = 0.009) and in 93.0% and 74.1% at 1 year (P = 0.038) in patients with AFMR-IAD and AFMR-AH, respectively. AFMR-AH was associated with procedural failure (OR: 1.17 [95% CI: 1.00-1.38]; P = 0.045) at 30 days (43.4% vs 24.0%; P = 0.023) and all-cause mortality (HR: 2.54 [95% CI: 1.09-5.91]; P = 0.031) at 1 year (77% vs 92%, Kaplan-Meier estimated 1-year survival; P = 0.017). AFMR-AH shows worse procedural and clinical outcomes following M-TEER than AFMR-IAD. Thus, vigilance regarding this pathology is warranted and alternative mitral valve therapies might need to be considered.

Myocardial infarction (MI) is a leading cause of morbidity and mortality worldwide. Improved survival has led to an increasing incidence of ischemic cardiomyopathy, making it a major reason for hospitalization in the western world. The inflammatory response in the ischemic myocardium determines the extent of structural remodeling and functional deterioration, with neutrophils (PMN) being a key modulator of the propagation and resolution of inflammation. The heme enzyme myeloperoxidase (MPO) is abundantly expressed in PMN and is an important mediator of their inflammatory capacities. Here, we examine the effects of PMN reduction, MPO deficiency and MPO inhibition in two murine models of MI. Reduction in PMN count resulted in less scar formation and improved cardiac function. Similar results were obtained in genetically MPO deficient mice, suggesting that MPO is a critical factor in PMN-mediated cardiac remodeling. To test our findings in a therapeutic approach, we orally administered the MPO inhibitor AZM198 in the context of MI and could demonstrate improved cardiac function and reduced structural remodeling. Therefore, MPO appears to be a favorable pharmacological target for the prevention of long-term morbidity after MI.

Secondary mitral regurgitation (SMR) has 2 phenotypes: atrial (aSMR) and ventricular (vSMR). The role of mitral valve transcatheter edge-to-edge repair (M-TEER) in aSMR remains less defined, with limited evidence on the PASCAL implant (Edwards Lifesciences). The authors sought to evaluate and compare outcomes of SMR phenotypes undergoing M-TEER. REPAIR (REgistry of PAscal for mItral Regurgitation) is an investigator-initiated, multicenter registry of patients undergoing M-TEER. aSMR was defined by left atrial dilation with preserved left ventricular size and ejection fraction. Outcomes included MR ≤1+ at discharge, technical success, NYHA functional class improvement, and 1-year survival. Among 915 patients (166 [18%] aSMR, 749 [82%] vSMR), the median follow-up was 491 days (Q1-Q3: 360-833 days). MR ≤1+ was achieved in 77.2% vs 71.4% (P = 0.162), with technical success in 97.0% vs 98.3% (P = 0.446). NYHA functional class improved in both phenotypes (P < 0.001), with 61.2% vs 61.3% in functional class ≤II at follow-up (P > 0.999). One-year survival was 88.4% (95% CI: 82.8%-94.4%) vs 86.0% (95% CI: 83.1%-89.0%; P = 0.346). In aSMR patients, 1-year survival was significantly lower in patients with baseline tricuspid regurgitation (TR) grade ≥moderate compared with those with <moderate TR (84.3% [95% CI: 77.0%-92.3%] vs 100.0% [95% CI: 100.0%-100.0%]; P = 0.041). In vSMR patients, survival was similar between ≥moderate and <moderate baseline TR (83.9% [95% CI: 79.8%-88.2%] vs 89.3% [95% CI: 85.0%-93.8%]; P = 0.051). M-TEER effectively reduces MR to ≤1+ and improves symptoms in both aSMR and vSMR. Particularly in aSMR, ≥moderate baseline TR is linked to worse outcomes, warranting consideration as an additional treatment target.

Prosthesis-patient mismatch after transcatheter aortic valve replacement (TAVR) can be measured echocardiographically (measured prosthesis-patient mismatch [PPMm]) or predicted (predicted prosthesis-patient mismatch [PPMp]) using published effective orifice area (EOA) reference values. However, the clinical implications of PPM post-TAVR remain unclear. This study aimed to elucidate the prevalence of PPMm and PPMp post-TAVR and their impact on mortality in a large international cohort. The IMPPACT TAVR (Impact of Measured or Predicted Prosthesis-pAtient mismatCh after TAVR) registry included 38,808 TAVR patients from 26 international centers. Valve Academic Research Consortium 3 criteria were used to define prosthesis-patient mismatch severity. EOA was determined echocardiographically (PPMm) or predicted (PPMp) based on core lab-derived EOA reference values. The primary endpoint was 2-year all-cause mortality. The prevalence of PPMp (moderate: 6.8%, severe: 0.6%) was significantly lower than that of PPMm (moderate: 20.7%, severe: 4.3%; P < 0.001) with negligible correlation between the 2 methods (Kendall's tau c correlation coefficient: 0.063; P < 0.001). In unadjusted analyses, severe PPMm adversely influenced 2-year survival (HR: 1.22; 95% CI: 1.02-1.45; P = 0.027), whereas severe PPMp was not associated with outcomes (HR: 0.81; 95% CI: 0.55-1.19; P = 0.291). After adjusting for confounders, neither PPMm nor PPMp had a significant effect on 2-year all-cause mortality. PPMm and PPMp were associated with different patient characteristics, with PPMm tending toward worse (especially low flow) and PPMp toward better (especially women) survival. After adjusting for confounders, neither PPMm nor PPMp significantly affected 2-year all-cause mortality. Hence, valve selection should not solely be based on hemodynamics but rather on a holistic approach, including patient and procedural specifics.

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

Aims: Patients suffering from Marfan syndrome (MFS), the most prevalent inherited connective tissue disorder, face premature mortality due to dissection and rupture of thoracic aortic aneurysms. Here, we questioned whether myeloperoxidase (MPO), a leucocyte-derived enzyme with high affinity to the vessel wall, contributes to aortic remodelling in MFS. Methods and results: Plasma MPO levels were evaluated in MFS patients and healthy controls. Thoracic aortic aneurysm formation was determined in heterozygous transgenic Fbn1C1041G/+ (MFS) mice, MPO-deficient MFS mice (MFSxMpo−/−), and MFS mice treated with an MPO inhibitor by ultrasound and histology. MFS patients exhibited increased circulating MPO levels and marked aortic MPO deposition. In MFS mice, MPO-deficiency reduced aortic elastin fragmentation and aneurysm formation. RNA sequencing revealed an inflammatory gene program in aortic endothelial cells isolated from MFS mice in comparison to WT and MFSxMpo−/− mice. This was accompanied by enhanced endothelial expression of the leucocyte adhesion molecule ICAM-1, increased leucocyte adhesion, and, consequently, leucocyte infiltration in MFS aortae. Moreover, MPO directly contributed to adverse extracellular matrix remodelling through overproduction of reactive oxygen species and subsequent vascular protein modifications leading to enhanced matrix metalloproteinase 2/9 activity. Lastly, treatment of MFS mice with the orally available MPO inhibitor AZM198 attenuated TAA formation. Conclusion: MPO is increased in MFS and contributes to thoracic aortic dilatation by inducing inflammatory endothelial activation, oxidative stress, and adverse extracellular matrix remodelling. Pharmacological and genetic inhibition of MPO reduced MFS-related aortic dilation in mice, highlighting MPO as a promising therapeutic target in MFS.