Abstract and Introduction
This is a joint position statement of the British Society of Echocardiography, the British Heart Valve Society and the Society for Endocrinology on the role of echocardiography in monitoring patients receiving dopamine agonist (DA) therapy for hyperprolactinaemia.
Evidence that DA pharmacotherapy causes abnormal valve morphology and dysfunction at doses used in the management of hyperprolactinaemia is extremely limited. Evidence of clinically significant valve pathology is absent, except for isolated case reports around which questions remain.
Attributing change in degree of valvar regurgitation, especially in mild and moderate tricuspid regurgitation, to adverse effects of DA in hyperprolactinaemia should be avoided if there are no associated pathological changes in leaflet thickness, restriction or retraction. Note must be taken that even where morphological change in leaflet structure and function may be suspected, grading is semi-quantitative on echocardiography and may vary between different machines, ultrasound settings and operators.
Decisions regarding discontinuation of medication should only be made after review of serial imaging by an echocardiographer experienced in analysing drug-induced valvulopathy or carcinoid heart disease.
A standard transthoracic echocardiogram should be performed before a patient starts DA therapy for hyperprolactinaemia. Repeat transthoracic echocardiography should then be performed at 5 years after starting cabergoline in patients taking a total weekly dose less than or equal to 2 mg. If there has been no change on the 5-year scan, repeat echocardiography could continue at 5-yearly intervals. If a patient is taking more than a total weekly dose of 2 mg, then annual echocardiography is recommended.
It is more than 10 years since the publication of a large population-based nested case-control study and an echocardiographic prevalence study reporting an association between the use of pergolide and cabergoline for the treatment of symptomatic Parkinson's disease (PD) and an increased risk of restrictive valvular heart disease. These and other studies led to the voluntary withdrawal of pergolide from the US market in 2007. While pergolide was used predominantly in PD, cabergoline is used more commonly in the treatment of hyperprolactinaemia. Dopamine agonists (DA) are first-line therapy for the treatment of hyperprolactinaemia because of excellent biochemical and tumoral control in the majority of patients, the alternative being surgery with or without radiotherapy, exposing patients to the risks of hypopituitarism. Cabergoline is generally the agent of choice because alternatives, such as bromocriptine, require multiple daily doses and have a less favourable side effect profile. The use of cabergoline in PD and hyperprolactinaemia differs considerably. Cabergoline is used in PD patients over a shorter period (months) at much higher dose (typically 3 mg a day) compared to a much longer period of treatment (years) at lower doses (typically 0.5-1 mg weekly) in hyperprolactinaemic patients. Moreover, while there are a number of effective alternative drugs in the treatment of PD, medical options for the treatment of hyperprolactinaemia are more limited. As a result of the studies documenting an increased risk of valulopathy in PD patients, the Medicines and Healthcare products Regulatory Agency (MHRA) recommended that physicians in the United Kingdom should request baseline echocardiography to exclude valvular heart disease in all patients before starting cabergoline or bromocriptine, followed by a second echocardiogram performed 3-6 months after commencement and then at 6-12-month intervals while continuing on the medication. It was also recommended that treatment be stopped if echocardiography showed worsening or new valvular restriction, thickening or regurgitation. In the intervening years, much echocardiographic data from cabergoline-treated hyperprolactinaemic patients has been published. Most of these data suggest that the risk of developing significant valvular heart disease is negligible and not a cause for clinical concern. Despite this, constraints imposed by the working relationship between the MHRA and the EMA dictate that the published recommendations are unlikely to be revised. This Position Statement, endorsed by the British Society of Echocardiography (BSE), the British Heart Valve Society (BHVS) and the Society for Endocrinology (SfE) has been written to provide endocrine and cardiac physicians with practical guidance in this area based on a contemporary review of the available literature.
Clin Endocrinol. 2019;90(5):662-669. © 2019 Blackwell Publishing