Hyperhomocysteinemia and mitral valve calcification in rheumatic heart disease: insights from a novel multi-modality imaging approach

Background Hyperhomocysteinemia is a risk factor for cardiovascular disease, but its impact on valve disease is lacking in research. Purpose This study aimed to evaluate the effect of hyperhomocysteinemia on rheumatic mitral valve disease. Methods A total of 672 patients with severe rheumatic mitral stenosis who underwent surgical intervention between January 2016 and December 2022 were included. Patients were stratified into two groups based on preoperative serum homocysteine levels: a hyperhomocysteinemia group (N=464) and a normal homocysteine group (N=208). A comprehensive multi-modality imaging protocol, integrating echocardiography and coronary computed tomography angiography, was employed to quantitatively assess mitral valve calcification using Agatston scores and volumetric measurements. Results Among the 672 patients, 464 (69.0%) exhibited hyperhomocysteinemia. These patients were older (60.06 vs. 58.06 years, P=0.002) and had a higher proportion of males (44.2% vs. 25.9%, P<0.001). Multi-modality imaging revealed significantly greater mitral valve calcification in the hyperhomocysteinemia group, as evidenced by higher Agatston scores (44.00 vs. 14.00, P=0.025) and larger calcification volumes (39.30 vs. 16.55 mm³, P=0.017). Additionally, these patients had larger left ventricular end-systolic diameters (36.00 vs. 33.00 mm, P=0.006), larger left atrial sizes (51.00 vs. 50.00 mm, P<0.001), and lower left ventricular ejection fractions (58.00% vs. 59.00%, P=0.040). Restricted cubic spline analysis demonstrated that homocysteine levels above 15 μmol/L were associated with a progressive increase in mitral valve calcification (P<0.001). Surgical outcomes were also adversely affected, with a lower rate of mitral valve repair (57.7% vs. 70.5%, P=0.002) and longer postoperative ICU stays (14.00 vs. 13.00 days, P=0.043). Over a median follow-up of 40.3 months, Kaplan-Meier analysis revealed significantly reduced mid-term survival in the hyperhomocysteinemia group (Log-rank P=0.004). Multivariate COX regression analysis identified hyperhomocysteinemia as an independent predictor of mid-term mortality (HR, 2.257; P=0.048). Conclusion This study demonstrates a significant association between hyperhomocysteinemia and mitral valve calcification in rheumatic heart disease. Hyperhomocysteinemia exacerbates valvular calcification and adversely impacts mid-term survival. Whether lowering homocysteine levels through pharmacological interventions improves outcomes in these patients warrants further prospective investigation.