Association of Altered Collagen Content and Lysyl Oxidase Expression in Degenerative Mitral Valve Disease

Background—Collagen cross-linking is mediated by lysyl oxidase (LOX) enzyme in the extracellular matrix (ECM) of mitral valve leaflets. Alterations in collagen content and LOX protein expression in the ECM of degenerative mitral valve may enhance leaflet expansion and disease severity. Methods—Twenty posterior degenerative mitral valve leaflets from patients with severe mitral regurgitation were obtained at surgery. Five normal posterior mitral valve leaflets procured during autopsy served as controls. Valvular interstitial cells (VICs) density was quantified by immunohistochemistry, collagen types I and III by picro-sirius red staining and immunohistochemistry, and proteoglycans by alcian blue staining. Protein expression of LOX and its mediator TGFβ1 were quantified by immunofluorescence and gene expression by PCR. Results—VICs density was increased, structural type I collagen density was reduced, while reparative type III collagen and proteoglycan densities were increased (p \u3c 0.0001) with an increase in spongiosa layer thickness in myxomatous valves. These changes were associated with a reduction in LOX (p \u3c 0.0001) and increase in TGFβ1 protein expression (p \u3c 0.0001). However, no significant change was seen in gene expression. Linear regression analysis identified a correlation between type I collagen density and LOX grade (R2 = 0.855; p \u3c 0.0001). Conclusions—Reduced type I collagen density with a simultaneous increase in type III collagen and proteoglycan densities possibly contributes to spongiosa layer expansion resulting in incompetent mitral valve leaflets. Observed changes in type I and III collagen densities in DMVD may be secondary to alterations in LOX protein expression, contributing to disorganization of ECM and disease severity

Incidence, Patterns, and Associations Between Dual-Antiplatelet Therapy Cessation and Risk for Adverse Events Among Patients With and Without Diabetes Mellitus Receiving Drug-Eluting Stents: Results From the PARIS Registry.

OBJECTIVES: The aim of this study was to examine the frequency and clinical impact of different cessation patterns of dual-antiplatelet therapy (DAPT) after percutaneous coronary intervention with drug-eluting stents among patients with and those without diabetes mellitus (DM). BACKGROUND: Early DAPT suspension after percutaneous coronary intervention increases the risk for major adverse cardiac events. However, temporal variability in risk and relation to DAPT cessation patterns among patients with DM remain unclear. METHODS: Using data from the PARIS (Patterns of Non-Adherence to Anti-Platelet Regimens in Stented Patients) registry, 1,430 patients with DM (34%) and 2,777 without DM (66%) treated with drug-eluting stents were identified. DAPT cessation modes were classified as temporary interruption (<14 days), disruption because of bleeding or poor compliance, and physician-recommended discontinuation. RESULTS: During 2-year follow-up, DM was associated with an increased risk for thrombotic events but a similar risk for bleeding. The cumulative incidence of DAPT cessation was significantly lower in patients with versus those without DM (50.1% vs. 55.4%; p < 0.01), driven largely by less frequent physician-guided discontinuation beyond 1 year. In contrast, 2-year rates of interruption and disruption were similar between groups. When DAPT was interrupted or discontinued under physician guidance, the risk for major adverse cardiac events was unchanged compared with patients with DM on uninterrupted DAPT. Conversely, when DAPT was disrupted, the risk for major adverse cardiac events increased compared with uninterrupted DAPT, regardless of diabetic status, with no evidence of statistical interaction. CONCLUSIONS: DAPT cessation patterns vary according to diabetic status, with less frequent physician-guided discontinuation among patients with DM. The presence of DM does not emerge as a modifier of cardiovascular risk after DAPT cessation

Causes, Timing, and Impact of Dual Antiplatelet Therapy Interruption for Surgery (From the PARIS Registry)

Temporary interruption of dual antiplatelet therapy (DAPT) is not infrequently required in patients undergoing percutaneous coronary intervention (PCI). We sought to describe the procedures and outcomes associated with DAPT interruption in patients treated with DAPT following successful PCI from the Patterns of non-adherence to anti-platelet regimens in stented patients registry (n = 5018). DAPT interruption was prespecified as physician recommended cessation forcohort, 490 patients (9.8%) experienced 594 DAPT interruptions over 2 years following PCI. Only 1 antiplatelet agent was interrupted in 57.2% cases and interruption was frequently recommended by noncardiologists (51.3%). Where type of surgery was reported, majority of DAPT interruptions occurred for minor surgery (68.4% vs 31.6%) and a similar cessation pattern of single versus dual antiplatelet cessation was observed regardless of minor or major surgery. Subsequent to DAPT interruption, 12 patients (2.4%) experienced 1 thrombotic event each, of which 5 (1.0%) occurred during the interruption period. All events occurred in patients who either stopped both agents (8 of 12) or clopidogrel-only (4 of 12), with no events occurring due to aspirin cessation alone. In conclusion, in the Patterns of Non-adherence to Anti-platelet Regiments in Stented Patients registry, 1 in 10 patients were recommended DAPT interruption for surgery within 2 years of PCI. Interruption was more common for a single agent rather than both antiplatelet agents regardless of severity of surgery, and was frequently recommended by noncardiologists. Only 1% of patients with DAPT interruption experienced a subsequent thrombotic event during the interruption period, which mainly occurred in patients stopping both antiplatelet agents