Cabergoline-Related Severe Restrictive Mitral Regurgitation
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《新英格兰医药杂志》
To the Editor: A 74-year-old man presented with progressive and severe dyspnea of two months' duration. The patient had Parkinson's disease that had initially been treated with levodopa, to which cabergoline had been added during the preceding four months. The physical examination was notable for increased jugular venous pressure, bilateral rales, and edema in both legs. On auscultation, a gallop rhythm and a 2/6 pansystolic murmur radiating to the axilla were noted. A chest radiograph showed mild cardiomegaly and signs of acute pulmonary edema. Electrocardiography demonstrated sinus rhythm at 80 beats per minute with left atrial enlargement. Transthoracic echocardiography revealed severe mitral regurgitation through thickened, retracted mitral leaflets with incomplete coaptation (Figure 1A, Figure 1B, and Figure 1C). Since there was no commissural or chordal fusion, a rheumatic cause was unlikely. The excursion of the mitral leaflets was severely impaired. Echocardiography four months earlier had shown no mitral-valve disease. Serum levels of 5-hydroxytryptamine and urinary 5-hydroxyindoleacetic acid were within normal limits.
Figure 1. Cardiac Images and Histologic Specimen of the Patient.
Transthoracic echocardiography in an apical three-chamber view shows the heart during diastole (Panel A) and systole (Panel B). Diastolic excursion is limited. During systole, there is a lack of coaptation (arrow, Panel B) of the thickened mitral leaflets. Color Doppler examination of the mitral valve in an apical four-chamber view shows the presence of a large regurgitant jet (Panel C). A histologic sample (Panel D) from the excised subvalvular apparatus (stained with hematoxylin and eosin) shows encasement of the tendinous cord (arrow) by proliferative plaque-like material consisting of myofibroblasts within a fibromyxoid stroma (arrowhead). Similar findings were noted in samples of the valve leaflets. LV denotes left ventricle, RV right ventricle, LA left atrium, and RA right atrium.
Heart failure persisted despite pharmacologic therapy, so the mitral valve was surgically replaced with a mechanical prosthesis. In the gross pathological examination of the mitral valve, the leaflets and the tendinous cords were thickened, with plaque-like encasement of valvular structures. Histologic analysis showed that the plaque-like material consisted of myofibroblasts within a fibromyxoid stroma (Figure 1D). After discharge from the hospital, the patient has been in good health without cardiac symptoms.
The echocardiographic features, the gross anatomy, and the microscopical characteristics of the mitral valve in our patient resemble those described with the use of antimigraine ergot alkaloid agents (ergotamine and methysergide), appetite suppressants (fenfluramine and dexfenfluramine), other dopaminergic agonists derived from ergotamine (pergolide), and the carcinoid syndrome.1,2,3 All these potential causes were excluded. However, this patient was taking cabergoline, an ergot-derivative drug with dopaminergic effects used in Parkinson's disease, the restless legs syndrome, and hyperprolactinemic disorders. Given the time course, the chemical similarity of cabergoline to other ergot derivatives, and the absence of any other offending agent, we conclude that cabergoline was most likely responsible for the development of valvular heart disease in this patient.
Cabergoline also prolongs the duration of orgasm in men.4 This drug is being offered illegally through the Internet5 and appears to have the potential for abuse. The medical community and the lay public should be aware of the serious side effect observed in our patient.
Antonio Pinero, M.D.
Pedro Marcos-Alberca, M.D.
Jose Fortes, M.D.
Fundación Jiménez Díaz
Madrid 28040, Spain
pmarcos@fjd.es
References
Redfield MM, Nicholson WJ, Edwards WD, Tajik AJ. Valve disease associated with ergot alkaloid use: echocardiographic and pathologic correlations. Ann Intern Med 1992;117:50-52.
Connolly HM, Crary JL, McGoon MD, et al. Valvular heart disease associated with fenfluramine-phentermine. N Engl J Med 1997;337:581-588.
Van Camp G, Flamez A, Cosyns B, et al. Treatment of Parkinson's disease with pergolide and relation to restrictive valvular heart disease. Lancet 2004;363:1179-1183.
Kruger TH, Haake P, Haverkamp J, et al. Effects of acute prolactin manipulation on sexual drive and function in males. J Endocrinol 2003;179:357-365.
BBC News. Sex drug could aid male stamina. April 24, 2002. (Accessed October 13, 2005, at http://news.bbc.co.uk/1/hi/health/1949087.stm.)
Figure 1. Cardiac Images and Histologic Specimen of the Patient.
Transthoracic echocardiography in an apical three-chamber view shows the heart during diastole (Panel A) and systole (Panel B). Diastolic excursion is limited. During systole, there is a lack of coaptation (arrow, Panel B) of the thickened mitral leaflets. Color Doppler examination of the mitral valve in an apical four-chamber view shows the presence of a large regurgitant jet (Panel C). A histologic sample (Panel D) from the excised subvalvular apparatus (stained with hematoxylin and eosin) shows encasement of the tendinous cord (arrow) by proliferative plaque-like material consisting of myofibroblasts within a fibromyxoid stroma (arrowhead). Similar findings were noted in samples of the valve leaflets. LV denotes left ventricle, RV right ventricle, LA left atrium, and RA right atrium.
Heart failure persisted despite pharmacologic therapy, so the mitral valve was surgically replaced with a mechanical prosthesis. In the gross pathological examination of the mitral valve, the leaflets and the tendinous cords were thickened, with plaque-like encasement of valvular structures. Histologic analysis showed that the plaque-like material consisted of myofibroblasts within a fibromyxoid stroma (Figure 1D). After discharge from the hospital, the patient has been in good health without cardiac symptoms.
The echocardiographic features, the gross anatomy, and the microscopical characteristics of the mitral valve in our patient resemble those described with the use of antimigraine ergot alkaloid agents (ergotamine and methysergide), appetite suppressants (fenfluramine and dexfenfluramine), other dopaminergic agonists derived from ergotamine (pergolide), and the carcinoid syndrome.1,2,3 All these potential causes were excluded. However, this patient was taking cabergoline, an ergot-derivative drug with dopaminergic effects used in Parkinson's disease, the restless legs syndrome, and hyperprolactinemic disorders. Given the time course, the chemical similarity of cabergoline to other ergot derivatives, and the absence of any other offending agent, we conclude that cabergoline was most likely responsible for the development of valvular heart disease in this patient.
Cabergoline also prolongs the duration of orgasm in men.4 This drug is being offered illegally through the Internet5 and appears to have the potential for abuse. The medical community and the lay public should be aware of the serious side effect observed in our patient.
Antonio Pinero, M.D.
Pedro Marcos-Alberca, M.D.
Jose Fortes, M.D.
Fundación Jiménez Díaz
Madrid 28040, Spain
pmarcos@fjd.es
References
Redfield MM, Nicholson WJ, Edwards WD, Tajik AJ. Valve disease associated with ergot alkaloid use: echocardiographic and pathologic correlations. Ann Intern Med 1992;117:50-52.
Connolly HM, Crary JL, McGoon MD, et al. Valvular heart disease associated with fenfluramine-phentermine. N Engl J Med 1997;337:581-588.
Van Camp G, Flamez A, Cosyns B, et al. Treatment of Parkinson's disease with pergolide and relation to restrictive valvular heart disease. Lancet 2004;363:1179-1183.
Kruger TH, Haake P, Haverkamp J, et al. Effects of acute prolactin manipulation on sexual drive and function in males. J Endocrinol 2003;179:357-365.
BBC News. Sex drug could aid male stamina. April 24, 2002. (Accessed October 13, 2005, at http://news.bbc.co.uk/1/hi/health/1949087.stm.)