Valvular heart disease in patients with prolactinomas on cabergoline treatment

Dopamine agonists are the first line treatment of prolactinomas and Parkinson’s disease. Ergot dopamine agonists have been associated with the development of (moderate to severe) clinically significant valvular thickening and retraction in patients with Parkinson’s disease heart valve insufficiency. In patients receiving dopamine agonists for hyperprolactinemia, most studies show no increased risk of valvulopathy. Objective: The objective was to document any possible association between the use of cabergoline (CB) in patients with prolactinomas treated at the clinic of Endocrinology and Metabolism Clinics Hospital and echocardiographic findings of valvular heart disease. Furthermore, to assess the presence of alterations in the structure and function related to heart valve dose and duration of treatment with cabergoline. Methods: We performed an analytical, observational and retrospective study of such cases-matched controls. Data from 22 patients with prolactinomas treated with cabergoline for a minimum of six months, treated between 2010 and 2012. They were matched with a control group consisting of 22 healthy subjects’ staff members and patients attending this clinic, adjusted analyzed for age and sex. We performed transthoracic echocardiography with color Doppler on the same team, by a cardiologist experienced in echocardiography. Heart valve regurgitation was quantified according to the guidelines of the American Society of Echocardiography. Abnormal mitral or its peak as one greater than 5 mm valve thickening was defined. Results: There were no cases of moderate-severe valvular regurgitation in either group. The prevalence of mild regurgitation was similar between patients and controls. There were no cases of pulmonary valve insufficiency. Only three patients and three subclinical valvular fibrosis controls (p=0.66) was evidenced. There were no cases of abnormal mitral valve thickening and no significant differences between the average thickness of the mitral valve between the two groups (p=0.65). There was no thickening of the other leaflets. We not observe a correlation between the cumulative dose of cabergoline or duration of treatment and valvular regurgitation. We found a significant correlation between the cumulative dose of cabergoline and mitral valve thickness (p=0.002,r 2=0.37). If we exclude from the analysis the patient presented mitral valve thicker (3.8mm), who received the highest doses of cabergoline (1962), this correlation is not observed (p=0.753). We also found a correlation between the maximum dose of cabergoline and mitral valve thickness (p=0.0008). Again, excluding the single patient who received the maximum dose this correlation is not observed (p=0.116). We found no relationship between the mitral valve thickness and length of treatment (p=0.084). There was no increase in the mitral tenting area. Patients treated with cabergoline had an ejection fraction (LVEF) significantly lower (60.9%±1.97) than controls (64.8%±4.9) (p=0.004). Those with overweight-obesity had significantly lower LVEF (60%) compared to those with normal weight (65%) (p=0.045). No relationship between LVEF and sex, high blood pressure (hypertension), smoking, diabetes (DM), impaired fasting glucose (IFG), oral glucose (IOG) or dyslipidemia in either group met intolerance. Nor association between cumulative dose of cabergoline (p=0.64) or duration of treatment (p=0.93) with LVEF. Conclusion: Cabergoline at doses commonly used in patients with prolactinomas not associated with higher prevalence of clinically significant valvular regurgitation, but with greater thickness mitral valvular (though without being abnormal thickening) associated with the cumulative dose