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Original research article
Drug-associated valvular heart diseases and serotonin-related pathways: a meta-analysis
  1. Jacqueline H Fortier1,
  2. Beatrice Pizzarotti2,
  3. Richard E Shaw3,
  4. Robert J Levy4,
  5. Giovanni Ferrari5,
  6. Juan Grau1
  1. 1 Division of Cardiac Surgery, University of Ottawa Heart Institute, Ottawa, Ontario, Canada
  2. 2 Univeristà degli Studi di Pavia, Pavia, Italy
  3. 3 The Valley Hospital, Ridgewood, New Jersey, USA
  4. 4 Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania, USA
  5. 5 Department of Surgery, Columbia University, New York City, New York, USA
  1. Correspondence to Professor Giovanni Ferrari, Department of Surgery, Columbia University, NY 10032, USA; gf2375{at}


Objective Serotonergic appetite suppressants and ergot-derived dopamine agonists have been associated with drug-induced valvular heart disease. The purpose of this meta-analysis is to synthesise the current evidence of a link between several medications affecting sertonergic pathways and valvular heart disease.

Methods PubMed was searched to identify studies evaluating an association between medications with serotonergic activity and cardiac valvular pathology. Case reports, uncontrolled studies and in vitro studies were excluded. Relevant studies were assessed for quality and potential bias; those of adequate quality were included in a quantitative synthesis. Sensitivity analyses were conducted, and potential publication bias was examined.

Results There was a consistent, significant relationship between certain medications and heart valve disease, including serotonergic medications (OR 3.30, 95% CI 1.99 to 5.49) and dopaminergic medications (OR 2.56, 95% CI 1.68 to 3.91). Subanalyses, including analyses that limited exposure to a single medication or effects to a single heart valve were also consistently significant. Most studies were retrospective or observational in nature, with a higher risk of selection and presentation biases. There was significant heterogeneity and variability between studies, particularly when it came to dose and duration of exposure.

Conclusions There was a consistent, significant association between many medications that affect serotonergic pathways and valvular heart disease. Although many of these medications have been withdrawn from the market, some small studies suggest that recreational drug 3,4-methylenedioxy​methamphetamine and widely prescribed selective serotonin reuptake inhibitors may affect similar pathways.

  • valvular heart disease
  • meta-analysis

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  • Contributors The research question was developed by authors GF, BP, RJL and JG. The literature search and assessment of articles was completed by JHF and BP, with JG acting as a third assessor in case of a disagreement between authors. The analysis was conducted by JHF and RES. The interpretation was conducted by JHF, RES, RJL, GF and JG. The manuscript was drafted by JHF and JG, with significant intellectual revisions and input from BP, RES, RJL and GF.

  • Funding This work was supported by the following research grants and funds: National Institutes of Health (R01-HL131872 to GF and RJL), The Kibel Fund for Aortic Valve Research (to GF and RJL), The Valley Hospital Foundation ’Marjorie C Bunnel’ charitable fund (to GF and JG), and both Erin’s Fund and the William J Rashkind Endowment of the Children’s Hospital of Philadelphia (to RJL).

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data sharing statement The full set of data used in this analysis, including search terms and results, full set of records reviewed, quality assessments of articles, data extracted from articles and analyses conducted, will be maintained by the authors. They can be made available upon requested to the corresponding author.

  • Patient consent for publication Not required.

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