Drug-induced fibrotic valvular heart disease

Lancet. 2009 Aug 15;374(9689):577-85. doi: 10.1016/S0140-6736(09)60252-X.


The initial association between the development of valvular heart disease and drugs stems from observations made during the use of methysergide and ergotamine for migraine prophylaxis in the 1960s. Since then, the appetite suppressants fenfluramine and dexfenfluramine, the dopamine agonists pergolide and cabergoline, and more recently, the recreational drug ecstasy (3,4 methylenedioxymethamphetamine; MDMA) have been implicated. Results from clinical trials show that drug dose and treatment duration affect both the risk of developing the disease and its severity. The natural history of the disease remains unclear, although regression of valvular lesions after the end of treatment has been reported. Interference with serotonin metabolism and its associated receptors and transporter gene seems a likely mechanism for development of the drug-induced valvular heart disease. Physicians need to balance the benefits of continued therapy with these drugs against possible risks. Further investigation is needed to assist with treatment decisions. Continued vigilance is necessary because several commonly prescribed treatments interact with serotonergic pathways.

Publication types

  • Review

MeSH terms

  • Antiparkinson Agents / adverse effects*
  • Appetite Depressants / adverse effects*
  • Cabergoline
  • Dexfenfluramine / adverse effects
  • Dopamine Agonists / adverse effects
  • Drug Monitoring
  • Ergolines / adverse effects
  • Ergotamine / adverse effects
  • Fenfluramine / adverse effects
  • Fibrosis
  • Heart Valve Diseases / chemically induced*
  • Heart Valve Diseases / diagnosis
  • Heart Valves / pathology
  • Humans
  • Methysergide / adverse effects
  • Migraine Disorders / drug therapy
  • N-Methyl-3,4-methylenedioxyamphetamine / adverse effects
  • Patient Selection
  • Pergolide / adverse effects
  • Receptors, Serotonin / drug effects
  • Serotonin Agents / adverse effects*
  • Serotonin Plasma Membrane Transport Proteins / drug effects
  • Vasoconstrictor Agents / adverse effects*


  • Antiparkinson Agents
  • Appetite Depressants
  • Dopamine Agonists
  • Ergolines
  • Receptors, Serotonin
  • Serotonin Agents
  • Serotonin Plasma Membrane Transport Proteins
  • Vasoconstrictor Agents
  • Pergolide
  • Fenfluramine
  • Dexfenfluramine
  • N-Methyl-3,4-methylenedioxyamphetamine
  • Cabergoline
  • Ergotamine
  • Methysergide