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This study was aimed at investigating the impact of hyperhomocysteinemia on rheumatic mitral valve calcification and prognosis in patients undergoing surgery.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This study included 672 patients with severe rheumatic mitral valve stenosis who underwent surgery between January 2016 and December 2022. Patients were stratified by preoperative homocysteine levels. Mitral valve pathology was assessed by echocardiography and coronary CTA, with all\u2010cause mortality as the primary mid\u2010term endpoint.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Among this surgical cohort of 672 patients with severe rheumatic mitral stenosis, 208 (31.0%) patients were identified with hyperhomocysteinemia. Imaging assessment revealed that these patients had a higher Agatston score for mitral valve calcification (37.47 vs. 17.19,\n                      <jats:italic>p<\/jats:italic>\n                      = 0.038) after adjusting baseline data. Restricted cubic splines revealed a significant dose\u2013response relationship, with mitral valve calcification increasing progressively with higher homocysteine levels (\n                      <jats:italic>p<\/jats:italic>\n                      &lt; 0.001). The Kaplan\u2013Meier survival analysis showed that patients with hyperhomocysteinemia had significantly lower mid\u2010term survival rates (log\u2010rank\n                      <jats:italic>p<\/jats:italic>\n                      = 0.004). Through univariate and multivariate COX regression analyses, it was found that hyperhomocysteinemia was an independent risk factor affecting mid\u2010term postoperative survival (HR, 2.257;\n                      <jats:italic>p<\/jats:italic>\n                      = 0.048).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In patients undergoing surgery for rheumatic heart disease, hyperhomocysteinemia was associated with the formation of rheumatic mitral valve calcification and increased mid\u2010term postoperative mortality.<\/jats:p>\n                    <jats:p>\n                      <jats:bold>Trial Registration:<\/jats:bold>\n                      Chinese Clinical Trial Registry identifier ChiCTR2200067151\n                    <\/jats:p>\n                  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