👤 Damien Gruson

Structural valve degeneration (SVD) is the leading cause of late bioprosthetic valve failure. Lipoprotein(a) [Lp(a)] contributes to native aortic valve calcification, but its role in SVD is unclear. We investigated whether elevated Lp(a) is associated with SVD after bioprosthetic aortic valve replacement (AVR) and whether this differs between stenotic and regurgitant phenotypes. We studied 174 bioprosthetic AVR patients with available Lp(a) levels over a median echocardiographic follow-up of 7.3 years (1372 studies). SVD was defined by VARC-3 criteria, and associations were analysed with Fine-Gray competing risk models. Lp(a) was evaluated categorically (≤ or > 125 nmol/L) and continuously using spline modelling. During follow-up, 40 patients developed SVD (22 stenotic, 9 mixed, and 9 regurgitant). The 15-year cumulative incidence was 51% with a median onset at 14.8 years. Elevated Lp(a) was associated with a higher risk of overall SVD (62% vs. 47%; SHR 2.06, 95% CI 1.09-3.91; P = 0.026) and specifically with stenotic/mixed phenotypes (SHR 2.57, 95% CI 1.26-5.23; P = 0.009). No association was observed with regurgitant phenotypes (SHR 0.85, 95% CI 0.19-3.92; P = 0.84). After multivariable adjustment, elevated Lp(a) remained an independent predictor of stenotic/mixed SVD (adjusted SHR 3.00, 95% CI 1.48-6.07; P = 0.002). Spline modelling showed a linear dose-response, with each 25 nmol/L increase in Lp(a) conferring 13% higher risk. Elevated Lp(a) is independently associated with long-term risk of stenotic/mixed SVD. These findings highlight Lp(a) as a promising biomarker of prosthetic valve vulnerability and support investigation of emerging Lp(a)-lowering therapies to improve valve durability. Show less

The metabolic environment plays a crucial role in the development of heart failure (HF). Our prior research demonstrated that myo-inositol, a metabolite transported by the sodium-myo-inositol co-transporter 1 (SMIT-1), can induce oxidative stress and may be detrimental to heart function. However, plasmatic myo-inositol concentration has not been comprehensively assessed in large cohorts of patients with heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF). Plasmatic myo-inositol levels were measured using mass spectrometry and correlated with clinical characteristics in no HF subjects and patients with HFrEF and HFpEF from Belgian (male, no HF, 53%; HFrEF, 84% and HFpEF, 40%) and Canadian cohorts (male, no HF, 51%; HFrEF, 92% and HFpEF, 62%). Myo-inositol levels were significantly elevated in patients with HF, with a more pronounced increase observed in the HFpEF population of both cohorts. After adjusting for age, sex, body mass index, hypertension, diabetes, and atrial fibrillation, we observed that both HFpEF status and impaired kidney function were associated with elevated plasma myo-inositol. Unlike HFrEF, abnormally high myo-inositol (≥69.8 μM) was linked to unfavourable clinical outcomes (hazard ratio, 1.62; 95% confidence interval, [1.05-2.5]) in patients with HFpEF. These elevated levels were correlated with NTproBNP, troponin, and cardiac fibrosis in this subset of patients. Myo-inositol is a metabolite elevated in patients with HF and strongly correlated to kidney failure. In patients with HFpEF, high myo-inositol levels predict poor clinical outcomes and are linked to markers of cardiac adverse remodelling. This suggests that myo-inositol and its transporter SMIT1 may have a role in the pathophysiology of HFpEF. BECAME-HF was supported by Collaborative Bilateral Research Program Québec - Wallonie-Brussels Federation. Show less