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

Recommendations on Surveillance

Echocardiography is accepted as the gold standard technique for assessment of native valve structure and function.[34] The detection of changes in structure and function in native valves may be subtle and echocardiography should be performed by properly-trained, accredited professionals.[35] In each case, a standard transthoracic study should be performed following minimum standards.[36] In addition to this, however, careful attention should be taken to perform semi-quantitative assessment of valve structure and function to detect the changes typical of DA agonist therapy. Although there are no methods validated for assessment in DA agonist therapy per se, the changes to be detected are the same as those in patients with carcinoid heart disease, for which there are validated scoring systems with high feasibility and discriminatory value.[37] Of these, the most sensitive and specific is an echocardiographic scoring system that assesses leaflet thickening, mobility and morphology, severity of valvular regurgitation and stenosis, and the haemodynamic effects on (right) ventricular size and function with good inter-observer agreement.[38] Moreover, this incorporates assessment of all four cardiac valves, although focusses on haemodynamically-significant right-sided valvular lesions through secondary effects on right ventricular size and function, which have been most frequently identified in the literature in DA agonist therapy (Table 3). Although tenting area has been used to quantify stiffening, this has not been validated in large studies and repeatability and reproducibility are not known, so that this is not a recommended feature for screening and follow-up.

Given that one of the major difficulties with the existing literature is the separation of valve disease due to DA agonist therapy from pre-existing changes in valve structure and function, it is recommended that all patients starting DA agonist therapy should undergo a transthoracic echocardiogram before drug therapy is commenced (Table 4). An increase in valve score may then be interpreted in the clinical context, considering the age and sex of the patient, the impact of other factors on valve leaflet thickening, mobility and morphology (eg, ageing, chronic kidney disease), and likely impact of DA agonist (total dosage and exposure). The main problem in clinical practice will be the use of such a score in patients who have been on a DA agonist for some time and in whom there may be changes identified on echocardiography. There have been no prospective validation studies of a scoring system and therefore, it is not possible to give a value or 'score' above which a patient should be categorized as affected by DA-valvopathy. The sensitivity of the scoring system for identifying changes in patients with carcinoid increases with increasing score, with a median score in those affected 12 (range 8-21) and in those not affected 2 (IQR 1-3).[37] It could be argued that routinely performing a transthoracic echocardiogram before drug therapy is commenced may be unnecessary and that doing an echocardiogram if the dose is increased above 2 mg/wk may be sufficient. The approach in this guideline is conservative, since the existing case-control and longitudinal follow-up studies cannot definitively exclude a small effect in the longer term. Moreover, given the semi-quantitative nature of echocardiographic evaluation of the changes described in DA valvulopathy and the fact that some of these changes can be seen in other conditions, assessment before initiation of drug therapy is considered a pragmatic solution pending further data.

Given the worst-case scenario for potential progression based on the largest cohort with serial follow-up,[5] it is recommended that repeat transthoracic echocardiography should be performed at 5 years after starting cabergoline in patients taking a total weekly dose ≤2 mg. If there has been no change on the 5-year scan, repeat echocardiography could continue at 5-yearly intervals. Within this time interval, there has been no evidence of major clinical change affecting patient outcome. There is an option for annual surveillance with auscultation, although there are no data regarding accuracy of this approach relative to the use of echocardiography.[39] If a patient is taking a total weekly dose of more than 2 mg, then annual echocardiography is recommended, although the number of these patients is small (see Table 4). Once cabergoline has been stopped, no further echocardiography is warranted assuming that no moderate or severe valve abnormality has been identified.

Given that grading is semi-quantitative, with subjective assessment of leaflet thickening, mobility and morphology, it is vital that follow-up studies are cross-checked by a different observer blinded to the initial echocardiographic score. Specifically, where there is a discrepancy >2 points in score, an echocardiographer with experience of patient monitoring for DA valvulopathy or with experience in patients who have carcinoid heart disease should analyze the serial studies available in the patient before any decision is made regarding discontinuation of medication. It is critical to understand that changes in degree of regurgitation alone, for example from mild to moderate tricuspid regurgitation, should not on its own be sufficient to alter clinical management, especially without morphological change in leaflet motion, thickness or retraction.

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