SSRI Use, Gene Variant Linked to Faster Heart Valve Decline
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- Columbia University researchers led by Giovanni Ferrari, PhD, analyzed data from more than 9,000 patients who underwent mitral valve surgery for degenerative mitral regurgitation along with 100 valve biopsies, in a multicenter study published in Science Translational Medicine in 2023.
- Patients with DMR taking SSRIs such as fluoxetine (Prozac) and sertraline (Zoloft) needed mitral valve surgery at a younger age than those not on the antidepressants, according to Ferrari.
- The study identified a "long-long" variant of the 5-HTTLPR gene, linked to lower serotonin transporter activity, as associated with more frequent mitral valve surgery in DMR patients — their valve cells produced excess collagen and showed heightened sensitivity to fluoxetine in lab tests.
- In mice, animals lacking the SERT gene and normal mice given high-dose SSRIs both developed thickened mitral valves, providing biological support for an association first seen in patient records.
- Ferrari proposed that a DNA test for 5-HTTLPR via blood sample or mouth swab could identify DMR patients needing closer monitoring or earlier surgery, though clinical trials have not yet validated the approach and major guidelines still focus on imaging and symptoms.
- The team emphasized that healthy mitral valves appear unaffected by low SERT activity and the findings do not justify stopping antidepressants without medical guidance — the risk signal appeared only in valves already degenerating.
- A 2024 follow-up study found mice with deficient SERT activity developed fibrotic changes in cardiac valves, adding evidence accumulated since the original 2023 paper.
Why it matters: Among more than 9,000 surgical DMR patients studied, those carrying two copies of the 5-HTTLPR 'long' variant and taking SSRIs needed surgery at younger ages — a combination Ferrari proposes identifying via a simple DNA swab. Current major guidelines do not yet incorporate genetic testing for valve disease, leaving a gap between the research signal and bedside practice.
