Echocardiography and Monitoring Patients Receiving Dopamine Agonist Therapy for Hyperprolactinaemia

A Joint Position Statement of The British Society of Echocardiography, The British Heart Valve Society and The Society for Endocrinology

Richard Steeds; Craig Stiles; Vishal Sharma; John Chambers; Guy Lloyd; William Drake

Disclosures

Clin Endocrinol. 2019;90(5):662-669. 

In This Article

Pathophysiology

The possibility that cabergoline might cause cardiac valvulopathy is pharmacologically and mechanistically plausible. Like other ergot-based drugs (eg, methysergide and the weight loss drugs fenfluramine and dexfenfluramine), cabergoline binds to the serotonin receptor subtype 2B (5-HT2B) located on heart valves. Activation of these receptors induces valvular interstitial cell mitogenesis and proliferation, which in turn modifies the quantity and quality of the valvular extracellular matrix through actions on proteoglycans, collagen types I, III and IV, and matrix metalloproteinases.[6] As a result, valve leaflets and chords become thickened, retracted and stiff, leading most commonly to valvular regurgitation (Figure 1A,B). The histopathological appearance of valves affected by DA agonists is akin to that caused by carcinoid syndrome, with deposition of plaque-like material consisting of myofibroblasts within a fibromyxoid stroma.[7] An association was found between higher cumulative doses of pergolide and cabergoline and the severity of cardiac valvular regurgitation in PD patients and, in particular, with the mitral valve tenting area, a subclinical index of leaflet stiffening and thickening.[3] This quantitative method for measuring the impact of DA on valve function is important for the interpretation of the prolactinoma literature for a number of reasons. Firstly, without careful blinding, there is evidence that subjective assessment tends to result in over-estimation of valvulopathy.[8] Secondly, most studies report only the degree of valve regurgitation and any assessment of leaflet thickening and retraction is subjective. Thirdly machine settings are not standardized, particularly the use of fundamental instead of second harmonic imaging. Harmonic imaging is a technique that employs the resonance characteristics of tissue to produce images with higher resolution and fewer artefacts than conventional (fundamental) imaging. Harmonic imaging is the principal technique now used in echocardiography, but over-estimates leaflet thickness compared to fundamental imaging. Finally, most studies within the prolactinoma literature only reported on the prevalence of any valvular lesion as detected by echocardiography, without distinguishing cabergoline-associated valvulopathy from coincidental abnormalities that may often be found in patients in the UK of similar age to those studied.[9]

Figure 1.

A, Tilted parasternal long axis view of the tricuspid valve demonstrating thickening, retraction and fixation of the leaflets. B, Colour flow Doppler demonstrating severe tricuspid regurgitation (Video format can be found in the Supporting Information)

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