SSRIs, gene variant linked to earlier mitral valve surgery
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- Columbia researchers reviewing records of more than 9,000 patients who had mitral valve repair or replacement found that SSRI users with degenerative mitral regurgitation (DMR) required surgery at younger ages than non-users.
- Giovanni Ferrari, PhD, of Columbia and Robert J. Levy, MD, of Children's Hospital of Philadelphia co-led the multicenter study, published in Science Translational Medicine in 2023 with support from the National Heart, Lung, and Blood Institute.
- Patients with DMR carrying two copies of the 'long' variant of the 5-HTTLPR region of the serotonin transporter gene underwent mitral valve surgery more often than patients with other variants, the team reported.
- Mitral valve cells from patients with the 'long-long' variant produced more collagen and reacted more strongly to serotonin and fluoxetine than cells carrying other variants, suggesting a biological mechanism behind the clinical association.
- Mice lacking the SERT gene developed thicker mitral valves, as did normal mice given high-dose SSRIs — supporting the possibility that reduced serotonin reuptake can drive structural remodeling in susceptible valve tissue.
- Ferrari's team proposed a DNA test (blood draw or mouth swab) for 5-HTTLPR to identify DMR patients with low SERT activity who might need closer monitoring or earlier surgery — though such testing is not yet part of standard valve-care guidelines.
- The researchers cautioned that the human findings were observational, that SSRIs did not appear to damage healthy mitral valves, and that the signal emerged only in valves already showing degeneration.
Why it matters: Roughly one in ten DMR patients in the 9,000-person cohort on SSRIs and carrying the 'long-long' 5-HTTLPR variant may face earlier valve surgery — and currently no genetic screen exists in heart-valve guidelines to flag them. If validated, a simple DNA test could shift some DMR patients from symptom-driven monitoring toward earlier intervention to prevent heart failure.
