Background: Aortic stenosis (AS) is driven by progressive inflammatory and fibrocalcific processes regulated by circulating inflammatory and valve resident endothelial and interstitial cells. The impact of platelets, platelet-derived mediators, and platelet-monocyte interactions on the acceleration of local valvular inflammation and mineralization is presently unknown.

Methods: We prospectively enrolled 475 consecutive patients with severe symptomatic AS undergoing aortic valve replacement. Clinical workup included repetitive echocardiography, analysis of platelets, monocytes, chemokine profiling, aortic valve tissue samples for immunohistochemistry, and gene expression analysis.

Results: The patients were classified as fast-progressive AS by the median ∆Vmax of 0.45 m/s per year determined by echocardiography. Immunohistological aortic valve analysis revealed enhanced cellularity in fast-progressive AS (slow- versus fast-progressive AS; median [interquartile range], 247 [142.3-504] versus 717.5 [360.5-1234]; <0.001) with less calcification (calcification area, mm: 33.74 [27.82-41.86] versus 20.54 [13.52-33.41]; <0.001). MIF (macrophage migration inhibitory factor)-associated gene expression was significantly enhanced in fast-progressive AS accompanied by significantly elevated MIF plasma levels (mean±SEM; 6877±379.1 versus 9959±749.1; <0.001), increased platelet activation, and decreased intracellular MIF expression indicating enhanced MIF release upon platelet activation (CD62P, %: median [interquartile range], 16.8 [11.58-23.8] versus 20.55 [12.48-32.28], =0.005; MIF, %: 4.85 [1.48-9.75] versus 2.3 [0.78-5.9], <0.001). Regression analysis confirmed that MIF-associated biomarkers are strongly associated with an accelerated course of AS.

Conclusions: Our findings suggest a key role for platelet-derived MIF and its interplay with circulating and valve resident monocytes/macrophages in local and systemic thromboinflammation during accelerated AS. MIF-based biomarkers predict an accelerated course of AS and represent a novel pharmacological target to attenuate progression of AS.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11335082PMC
http://dx.doi.org/10.1161/ATVBAHA.124.321000DOI Listing

Publication Analysis

Top Keywords

aortic valve
12
aortic stenosis
8
fast-progressive median
8
aortic
5
macrophage migration
4
migration inhibitory
4
inhibitory factor
4
factor promotes
4
promotes thromboinflammation
4
thromboinflammation predicts
4

Similar Publications

Background: The aim of this study was to evaluate the prognostic impact of computed tomography (CT)-based body composition parameters in metabolically unhealthy normal-weight patients (MUHNW) with aortic stenosis (AS) undergoing transcatheter aortic valve replacement (TAVR).

Methods: This prospective cohort study involved adults with normal weight scheduled for TAVR. Patients were divided into two groups: metabolically healthy normal-weight (MHNW) and MUHNW.

View Article and Find Full Text PDF

Background: Patients with symptomatic aortic stenosis are a vulnerable population with associated cardiac damage and a significant comorbidity burden. This study aimed to determine the rate, factors associated with, and prognostic value of poor functional status (NYHA class III-IV) in patients with severe aortic stenosis undergoing transcatheter aortic valve replacement (TAVR).

Methods: This multicenter study included 6,363 transarterial TAVR patients, classified according to baseline functional status (NYHA class I-II vs.

View Article and Find Full Text PDF

Background: Low-gradient (LG) aortic stenosis (AS) has not been fully characterized compared with high-gradient (HG) AS in terms of cardiac damage, frailty, aortic valve calcification, and clinical outcomes.

Objectives: The aim of this study was to compare the clinical characteristics and outcomes between each hemodynamic type of LG AS and HG AS.

Methods: The current study included 3,363 patients in the CURRENT AS (Contemporary outcomes after sURgery and medical tREatmeNT in patients with severe Aortic Stenosis) Registry-2 after excluding patients without indexed stroke volume or left ventricular ejection fraction (LVEF) data.

View Article and Find Full Text PDF

Background: With the rapid expansion of transcatheter aortic valve replacement (TAVR), TAVR valve explantation is also increasing. Nevertheless, previous reports on Lotus Edge valve explantation are limited to only two reports, none of which include intraoperative videos. Therefore, we report the case of an older adult who underwent a 2-year-old Lotus Edge valve explantation, after developing prosthetic valve endocarditis (PVE) and aortic annular abscess, with a strong indication for a TAVR explantation and surgical aortic valve replacement (AVR).

View Article and Find Full Text PDF

Background: Acute heart failure due to aortic regurgitation (AR) is a severe comorbidity of type A acute aortic dissection (AAD). Valve-sparing aortic root replacement is typically performed when the aortic valve remains intact.

Case Presentation: A 33-year-old male presented to our hospital with chest pain.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!