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Science (New York, N.Y.) Jul 2023Atrial fibrillation disrupts contraction of the atria, leading to stroke and heart failure. We deciphered how immune and stromal cells contribute to atrial fibrillation....
Atrial fibrillation disrupts contraction of the atria, leading to stroke and heart failure. We deciphered how immune and stromal cells contribute to atrial fibrillation. Single-cell transcriptomes from human atria documented inflammatory monocyte and macrophage expansion in atrial fibrillation. Combining hypertension, obesity, and mitral valve regurgitation (HOMER) in mice elicited enlarged, fibrosed, and fibrillation-prone atria. Single-cell transcriptomes from HOMER mouse atria recapitulated cell composition and transcriptome changes observed in patients. Inhibiting monocyte migration reduced arrhythmia in HOMER mice. Cell-cell interaction analysis identified SPP1 as a pleiotropic signal that promotes atrial fibrillation through cross-talk with local immune and stromal cells. Deleting reduced atrial fibrillation in HOMER mice. These results identify SPP1 macrophages as targets for immunotherapy in atrial fibrillation.
Topics: Animals; Humans; Mice; Atrial Fibrillation; Heart Atria; Macrophages; Mitral Valve Insufficiency; Osteopontin; Gene Deletion; Cell Movement; Single-Cell Gene Expression Analysis
PubMed: 37440641
DOI: 10.1126/science.abq3061 -
EuroIntervention : Journal of EuroPCR... Nov 2023Mitral regurgitation is the second most frequent heart valve disease in Europe and the most frequent in the US. Although surgery is the therapy of choice when... (Review)
Review
Mitral regurgitation is the second most frequent heart valve disease in Europe and the most frequent in the US. Although surgery is the therapy of choice when intervention is indicated, transcatheter mitral valve repair or replacement are alternatives for patients who are not eligible for surgery. However, the development of transcatheter mitral valves is slower than expected. Although several transcatheter heart valves have been developed, only one has been commercialised. Indeed, most of these devices are being evaluated in clinical studies, with promising initial results. In this review, we propose an overview on transcatheter mitral valve replacement for the treatment of native mitral valve disease, from indication to results, including patients with severe annular calcification, and we provide you with a glimpse into the future of these therapies.
Topics: Humans; Mitral Valve; Heart Valve Prosthesis Implantation; Heart Valve Prosthesis; Treatment Outcome; Heart Valve Diseases; Mitral Valve Insufficiency; Cardiac Catheterization
PubMed: 37994096
DOI: 10.4244/EIJ-D-22-00890 -
The American Journal of Cardiology Nov 2023This systematic review and meta-analysis aimed to investigate whether percutaneous mitral valve repair (PMVr) using MitraClip was more effective than surgery or medical... (Meta-Analysis)
Meta-Analysis Review
This systematic review and meta-analysis aimed to investigate whether percutaneous mitral valve repair (PMVr) using MitraClip was more effective than surgery or medical therapy for long-term morbidity and mortality. We searched MEDLINE, EMBASE, and CENTRAL (Cochrane Library) databases to identify relevant studies that recruited adult patients with functional or secondary mitral valve regurgitation who underwent PMVr with MitraClip implantation using appropriate search terms and Boolean operators. The odds ratios (ORs) were pooled using the random-effects model. A total of 14 studies recruiting 2,593 patients were included. Within 12 months of follow-up, patients who underwent PMVr did not maintain mitral valve regurgitation grade 2+ (OR 0.22, 95% confidence interval [CI] 0.12 to 0.41, p <0.0001, I = 0.0%, p = 0.52) or symptom-free heart failure (OR 0.47, 95% CI 0.29 to 0.77, p = 0.0028, I = 0.0%, p = 0.66) compared with their surgical counterparts. Patients were more likely to be rehospitalized for heart failure (OR 2.79, 95% CI 1.54 to 5.05, p = 0.0007, I = 0.0%, p = 0.51). However, there was no difference between the groups in terms of all-cause or cardiovascular mortality. Whereas, in comparison with medical therapy, PMVr significantly reduced all-cause mortality at 12 and ≥24 months of follow-up (OR 0.41, 95% CI 0.24, 0.69, p = 0.0009, I = 32%, p = 0.23 and OR 0.55, 95% CI 0.40, 0.75, p = 0.0002, I = 0.0%, p = 0.45, respectively). In conclusion, there was no difference in all-cause death at 12 or 24 months of follow-up between PMVr and the surgical approach, but the durability of valvular repair was inferior with PMVr. In comparison with medical therapy, there was a significant reduction in mortality with PMVr.
Topics: Adult; Humans; Mitral Valve Insufficiency; Mitral Valve; Treatment Outcome; Cardiac Surgical Procedures; Heart Failure; Heart Valve Prosthesis Implantation
PubMed: 37741106
DOI: 10.1016/j.amjcard.2023.08.097 -
Circulation Research Sep 2023Cardiac valve disease is observed in 2.5% of the general population and 10% of the elderly people. Effective pharmacological treatments are currently not available, and...
BACKGROUND
Cardiac valve disease is observed in 2.5% of the general population and 10% of the elderly people. Effective pharmacological treatments are currently not available, and patients with severe cardiac valve disease require surgery. PROX1 (prospero-related homeobox transcription factor 1) and FOXC2 (Forkhead box C2 transcription factor) are transcription factors that are required for the development of lymphatic and venous valves. We found that PROX1 and FOXC2 are expressed in a subset of valvular endothelial cells (VECs) that are located on the downstream (fibrosa) side of cardiac valves. Whether PROX1 and FOXC2 regulate cardiac valve development and disease is not known.
METHODS
We used histology, electron microscopy, and echocardiography to investigate the structure and functioning of heart valves from mice in which was conditionally deleted from VECs. Isolated valve endothelial cells and valve interstitial cells were used to identify the molecular mechanisms in vitro, which were tested in vivo by RNAScope, additional mouse models, and pharmacological approaches. The significance of our findings was tested by evaluation of human samples of mitral valve prolapse and aortic valve insufficiency.
RESULTS
Histological analysis revealed that the aortic and mitral valves of mice become progressively thick and myxomatous. Echocardiography revealed that the aortic valves of mice are stenotic was downregulated and PDGF-B (platelet-derived growth factor-B) was upregulated in the VECs of mice. Conditional knockdown of FOXC2 and conditional overexpression of PDGF-B in VECs recapitulated the phenotype of mice. PDGF-B was also increased in mice lacking FOXC2 and in human mitral valve prolapse and insufficient aortic valve samples. Pharmacological inhibition of PDGF-B signaling with imatinib partially ameliorated the valve defects of mice.
CONCLUSIONS
PROX1 antagonizes PDGF-B signaling partially via FOXC2 to maintain the extracellular matrix composition and prevent myxomatous degeneration of cardiac valves.
Topics: Animals; Humans; Mice; Endothelial Cells; Heart Valve Diseases; Mitral Valve; Mitral Valve Prolapse; Transcription Factors; Proto-Oncogene Proteins c-sis
PubMed: 37555328
DOI: 10.1161/CIRCRESAHA.123.323027 -
Current Problems in Cardiology Oct 2023Many questions were raised due to the divergent results between cardiovascular outcomes assessment of the MitraClip percutaneous therapy for heart failure patients with... (Review)
Review
Many questions were raised due to the divergent results between cardiovascular outcomes assessment of the MitraClip percutaneous therapy for heart failure patients with functional mitral regurgitation (COAPT) and multicenter study of percutaneous mitral valve Repair MitraClip device in patients with severe secondary mitral regurgitation (MITRA-FR) trials on the use of percutaneous mitral valve repair for secondary mitral regurgitation. This paper examined pooled patients' characteristics and outcomes from real-life experience compared with those in the 2 landmark trials. A comprehensive search identified eligible studies published in 2020 and 2021. Mean difference and odds ratio (OR) were used to compare continuous and categorical data. Thirty-three studies included more than 9200 patients. Patients in landmark trials were younger than in real-life, less likely to present with severe heart failure symptoms ([COAPT: OR 0.25; 95% CI: 0.21, 0.31]; [MITRA-FR: OR 0.32; 95% CI: 0.23, 0.45]) or severe mitral regurgitation grade (COAPT only: OR 0.57; 95% CI: 0.45, 0.71) with larger left ventricular end diastolic volume. Procedure success (OR 1.94; 95% CI: 1.10, 3.40) was more frequent with lower all-cause mortality (OR 0.73; 95% CI: 0.54, 0.99) in COAPT. Real-life patients experienced more favorable procedural and clinical outcomes compared with MITRA-FR patients. Real-life data on percutaneous mitral valve repair in secondary mitral regurgitation showed important variations in patient selection and procedural outcomes. Rates of death and heart failure hospitalization in observational studies were lower than MITRA-FR but higher than COAPT trial.
Topics: Humans; Mitral Valve Insufficiency; Mitral Valve; Treatment Outcome; Heart Valve Prosthesis Implantation; Heart Failure; Multicenter Studies as Topic
PubMed: 37336309
DOI: 10.1016/j.cpcardiol.2023.101889 -
EuroIntervention : Journal of EuroPCR... Aug 2023Transcatheter mitral valve replacement (TMVR) using dedicated devices is an alternative therapy for high-risk patients with symptomatic mitral regurgitation (MR).
BACKGROUND
Transcatheter mitral valve replacement (TMVR) using dedicated devices is an alternative therapy for high-risk patients with symptomatic mitral regurgitation (MR).
AIMS
This study aimed to assess the 2-year outcomes and predictors of mortality in patients undergoing TMVR from the multicentre CHOICE-MI Registry.
METHODS
The CHOICE-MI Registry included consecutive patients with symptomatic MR treated with 11 different dedicated TMVR devices at 31 international centres. The investigated endpoints included mortality and heart failure hospitalisation rates, procedural complications, residual MR, and functional status. Multivariable Cox regression analysis was applied to identify independent predictors of 2-year mortality.
RESULTS
A total of 400 patients, median age 76 years (interquartile range [IQR] 71, 81), 59.5% male, EuroSCORE II 6.2% (IQR 3.8, 12.0), underwent TMVR. Technical success was achieved in 95.2% of patients. MR reduction to ≤1+ was observed in 95.2% at discharge with durable results at 1 and 2 years. New York Heart Association Functional Class had improved significantly at 1 and 2 years. All-cause mortality was 9.2% at 30 days, 27.9% at 1 year and 38.1% at 2 years after TMVR. Chronic obstructive pulmonary disease, reduced glomerular filtration rate, and low serum albumin were independent predictors of 2-year mortality. Among the 30-day complications, left ventricular outflow tract obstruction, access site and bleeding complications showed the strongest impact on 2-year mortality.
CONCLUSIONS
In this real-world registry of patients with symptomatic MR undergoing TMVR, treatment with TMVR was associated with a durable resolution of MR and significant functional improvement at 2 years. Two-year mortality was 38.1%. Optimised patient selection and improved access site management are mandatory to improve outcomes.
Topics: Humans; Male; Aged; Female; Mitral Valve; Heart Valve Prosthesis Implantation; Heart Valve Prosthesis; Cardiac Catheterization; Treatment Outcome; Risk Factors; Mitral Valve Insufficiency; Registries
PubMed: 37235388
DOI: 10.4244/EIJ-D-22-01037 -
The Journal of Invasive Cardiology Nov 2023Transcatheter edge-to-edge repair (TEER) using the MitraClip (Abbott Vascular) system has emerged as a standard treatment for patients with symptomatic severe secondary... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Transcatheter edge-to-edge repair (TEER) using the MitraClip (Abbott Vascular) system has emerged as a standard treatment for patients with symptomatic severe secondary or inoperable primary mitral regurgitation (MR). The relatively recent approval of the PASCAL Transcatheter Valve Repair System (Edwards Lifesciences) has expanded the options of TEER devices. However, evidence comparing PASCAL with MitraClip systems is still limited.
METHODS
We conducted a systematic literature research and meta-analysis in PubMed, Medline, and EMBASE databases for studies comparing PASCAL and MitraClip systems.
RESULTS
Four observational studies and 1 randomized controlled trial, involving 1315 patients total, were eligible for inclusion. All patients exhibited symptomatic (NYHA II-IV) MR grades 3+ or 4+. Baseline characteristics were comparable across all included studies. The clinical outcomes were assessed according to the Mitral Valve Academic Research Consortium consensus. The procedural success rates for the 2 devices were comparable in terms of achieving post-procedural MR grades of less than or equal to 2+ and less than or equal to 1+. Furthermore, most patients improved their clinical status, with no significant differences between patients treated with PASCAL and those treated with MitraClip. In terms of safety, both procedures exhibited low overall mortality rates and occurrence of major adverse events (MAE), without significant difference between the 2 devices. These findings remained consistent in both short- and long-term follow-up assessments.
CONCLUSIONS
Our study revealed similar effectiveness and safety profiles between the PASCAL and MitraClip devices in patients experiencing significant symptomatic MR.
Topics: Humans; Cardiac Catheterization; Cardiac Surgical Procedures; Catheters; Heart Valve Prosthesis Implantation; Mitral Valve; Mitral Valve Insufficiency; Treatment Outcome
PubMed: 37992330
DOI: 10.25270/jic/23.00218