The Third Case of Cabergoline-Associated Valvulopathy: The Value of Routine Cardiovascular Examination for Screening

Abstract

A decade after the alarming association of cabergoline-associated valvulopathy (CAV) in Parkinson disease, only two confirmed cases have occurred in patients with prolactinoma. Routine screening for CAV by echocardiography has not proved to be of diagnostic utility, has several limitations, and is not widely practiced. We have previously highlighted the value of annual cardiovascular examination as a screening tool for CAV in patients with prolactinoma. We present a case, now the third confirmed case of CAV, to highlight the value of the cardiovascular examination. A 52-year-old woman with a 25-year history of macroprolactinoma had received multimodal treatment, including surgery, radiosurgery, and medical therapy. Her medical therapy initially consisted of bromocriptine, followed by cabergoline. The cabergoline dose was 6 mg weekly. In 2009, the cumulative dose was 3272 mg when an echocardiogram showed no evidence of valvular disease. A routine cardiovascular examination in the clinic detected a new murmur in 2016. The echocardiogram demonstrated new-onset mild to moderate aortic regurgitation, with a thickened and restricted valve consistent with CAV. The cumulative dose of cabergoline at that point was 4192 mg. Follow-up echocardiography at 6-month intervals showed progression to moderate to severe aortic regurgitation, which has since stabilized. Cabergoline therapy was weaned and stopped completely in April 2017. An annual cardiovascular examination is the best screening test for CAV and can change the course of a patient’s treatment. Echocardiograms should be reserved for patients with a new-onset cardiac murmur or a high cumulative dose of cabergoline.

Epidemiology and Management Challenges in Prolactinomas

“…After a follow-up of at least four years, treated patients had no increased incidence of valvular disease versus controls [65]. [69].…”

Pharmacokinetics and pharmacodynamics of ropinirole in patients with prolactinomas

“…Bromocriptine is not tolerated in 12–36% patients, due to side effects including nausea and vomiting, headaches, dizziness and fatigue . In spite of a higher incidence of orthostatic hypotension, cabergoline is associated with fewer side effects overall, but its high affinity for the serotonin 5HT‐2B expressed in heart valves, may stimulate mitogenesis and fibroblastic proliferation, and promote the development of cardiac valve disease as has been observed in both Parkinson's and prolactinoma patients treated with the drug . While a single prospective study did not identify an increased risk of significant cardiac valve disease in the first 5 years of cabergoline treatment, the median cumulative dose exposure was relatively low (149 mg) and the 60 month follow‐up period is well below the treatment duration required for a significant percentage of prolactinoma patients, limiting its generalizability .…”

“…In spite of their efficacy, the ergot DAs lack specificity for the D2R subfamily and exhibit receptor cross‐reactivity that impacts tolerability . Additionally, cabergoline's affinity for the serotonin 5‐hydroxytryptamine receptor subtype 2B (5HT‐2B) expressed on cardiac valves has generated concerns about its overall safety . While long‐term prospective studies are needed to confirm a causative relationship between cabergoline and valvular heart disease in treated hyperprolactinaemics, patients and practitioners remain apprehensive about the implications of its use particularly in cases requiring high doses or prolonged therapy and in patients with pre‐existing valve disease.…”

Monitoring patients receiving dopamine agonist therapy for hyperprolactinaemia

“…Examining the wider literature there are 5 case reports in which cabergoline is the proposed mechanism behind cardiac valvulopathy and in which there is clinically significant cardiac failure (16)(17)(18)(19)(20). Whilst other mechanisms (co-existent gut carcinoid, previous bromocriptine therapy, growth hormone excess and prior, undiagnosed valvulopathy) remain plausible in some of these reports, it is important not to discount the possibility that cabergoline is, at least in part, implicated pathogenetically, particularly when administered in relatively high doses over long periods of time (21) .…”