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Heart valve disease in acromegaly
International Journal of Cardiology 90 (2003) 331–332 www.elsevier.com / locate / ijcard
Letter to the Editor
Heart valve disease in acromegaly ´ a , *, Vicente Climent a , Antonio M. Pico´ b , Juan G. Martınez ´ a, Eduardo Paya´ a , Francisco Marın Francisco Sogorb a a
b
Department of Cardiology, General Hospital of Alicante, C /Pintor Baeza s /n, 03002 Alicante, Spain Department of Endocrinology, General Hospital of Alicante, C /Pintor Baeza s /n, 03002 Alicante, Spain
Received 8 September 2002; received in revised form 23 September 2002; accepted 26 September 2002
Acromegaly is a multiple disorder resulting from a chronic increase in the secretion of growth hormone [1]. The relation between growth hormone and the cardiovascular system has raised great interest as a high prevalence of cardiovascular disease has been described in acromegalic patients [2] (mainly coronary heart disease, arrhythmias, and heart failure), and is the predominant cause of increased mortality in acromegaly. Nevertheless, there are few reports of valvular heart disease in acromegaly. We report three cases of severe valvular heart disease in acromegaly (Table 1): one mitral regurgitation, and two aortic regurgitations (which represents a prevalence of three cases of severe valve disease in our series of 47 acromegalic patients—6.4%). The first case is a 58-year-old man with heart failure. Echocardiographic study showed a myxomatous-like mitral valve with posterior leaflet prolapse and severe regurgitation. Furthermore, he presented a prolapse of the septal and posterior leaflets of the tricuspid valve, also myxomatous-like. The second case is a 57-year-old man; acromegaly was diagnosed 14 years before the diagnosis of a severe aortic regurgitation, non-rheumatic-like. The patient was operated on with a mechanical valve replacement. One year later he suffered an endo*Corresponding author. Tel.: 134-96-593-8358; fax: 134-96-5937722. ´ E-mail address: [email protected] (F. Marın).
carditis by Staphylococcus epidermidis over the prosthesis, proceeding to valve replacement. The third case is a 57-year-old man, for whom acromegaly was diagnosed 9 months before the diagnosis of a moderate–severe aortic regurgitation without cardiac symptoms. Ventricular hypertrophy is unequivocally known in acromegaly (our patients had severe hypertrophy in echocardiographic studies). The high prevalence of hypertension, diabetes and hyperinsulinism in acromegalic patients casts doubt on the existence of an authentic acromegalic heart muscle disease, secondary to growth hormone excess. Nevertheless, it has been verified in experimental studies that growth Table 1 Patient characteristics
Valve disease Age (years) Sex Hypertension Diabetes LVEDD (mm) LVESD (mm) S (mm) PW (mm) Shortening fraction (%) LV mass (g / m 2 )
Case 1
Case 2
Case 3
Mitral regurgitation 58 Male Yes No 72 50 17 13 30 242
Aortic regurgitation 57 Male Yes Yes 77 56 26 23 27 464
Aortic regurgitation 57 Male No Yes 63 42 17 15 33 195
LVEDD, left ventricular end diastolic diameter; LVESD, left ventricular end systolic diameter; S, septum; PW, posterior wall; LV mass, left ventricular mass.
0167-5273 / 03 / $ – see front matter 2003 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/S0167-5273(02)00527-2
332
E. Paya´ et al. / International Journal of Cardiology 90 (2003) 331–332
hormone, by itself, or by its mediator, insulin-like growth factor-1, produces ventricular hypertrophy with an increase of myocite inotropism. Other factors which suggest the existence of acromegalic cardiomyopathy are the high prevalence of right ventricular diastolic dysfunction [3], and, after treatment with lanreotide, an analog of somatostatin, there is a significant decrease in cardiac mass. Interestingly, acromegalic ventricular hypertrophy develops in the absence of any afterload increase [2]. Growth hormone has been demonstrated to stimulate the accumulation of certain sulphated mucopolysaccharides, which would produce myxomatous degeneration of the valves. A report from an acromegalic patient with mitral regurgitation showed myxomatous degeneration of all four cardiac valves and cystic medial necrosis of the aorta and pulmonary artery [4]. A Japanese report described five surgical cases: one case of aortic and mitral regurgitation, one of aortic regurgitation, and three of mitral regurgitation [5]. Histopathologic examination of the excised valves revealed mucopolysaccharide deposits on the leaflets, and the myocardium showed fibrosis of interstitial spaces and endocardium, and disarrangement and enlargement of muscle fibers. However, a review of 27 autopsied cases of acromegaly [6] revealed that valve disease was present in five cases (19%): two aortic regurgitation, two mitral stenosis and regurgitation (none was rheumatic or luetic in origin) and one calcified stenosis and regurgitation secondary to old, healed, bacterial endocarditis.
We may add that the late diagnose of valve disease in our patients (and probably in acromegaly in general) may be related to the slow course of acromegalic disease, together with factors such as obesity, arthralgias, and fatigue, which reduce life activities, and retard the symptoms secondary to valve disease. Both experimental and clinical data support the existence of an acromegalic cardiomyopathy. The features of this disease would consist of myocardial hypertrophy, interstitial fibrosis, and cellular infiltration consistent with myocarditis. Furthermore, in accordance with these findings, we would add that valve disease due to excess growth hormone should be taken into account in cardiac evaluation of acromegalic patients.
References [1] Melmed S. Acromegaly. New Engl J Med 1990;322:966–77. [2] Sacca´ L, Cittadini A, Fazzio S. Growth hormone and the heart. Endocr Rev 1994;15:555–73. ´ F, Pico´ A, Martınez ´ [3] Marın JG et al. Biventricular impairment in diastolic function in acromegaly. Rev Esp Cardiol 2001;54:37–42. [4] Ondreyco SM, Lewis Jr. HD, Hartman CR. Myxomatous degeneration and cystic medial necrosis associated with acromegaly. Arch Intern Med 1980;140:547–9. [5] Ohtsuka G, Aomi S, Koyanagi H et al. Heart valve operation in acromegaly. Ann Thorac Surg 1997;64:390–3. [6] Lie JT, Grossman SJ. Pathology on the heart in acromegaly: anatomic findings in 27 autopsied patients. Am Heart J 1980;100:41–52.
Letter to the Editor
Heart valve disease in acromegaly ´ a , *, Vicente Climent a , Antonio M. Pico´ b , Juan G. Martınez ´ a, Eduardo Paya´ a , Francisco Marın Francisco Sogorb a a
b
Department of Cardiology, General Hospital of Alicante, C /Pintor Baeza s /n, 03002 Alicante, Spain Department of Endocrinology, General Hospital of Alicante, C /Pintor Baeza s /n, 03002 Alicante, Spain
Received 8 September 2002; received in revised form 23 September 2002; accepted 26 September 2002
Acromegaly is a multiple disorder resulting from a chronic increase in the secretion of growth hormone [1]. The relation between growth hormone and the cardiovascular system has raised great interest as a high prevalence of cardiovascular disease has been described in acromegalic patients [2] (mainly coronary heart disease, arrhythmias, and heart failure), and is the predominant cause of increased mortality in acromegaly. Nevertheless, there are few reports of valvular heart disease in acromegaly. We report three cases of severe valvular heart disease in acromegaly (Table 1): one mitral regurgitation, and two aortic regurgitations (which represents a prevalence of three cases of severe valve disease in our series of 47 acromegalic patients—6.4%). The first case is a 58-year-old man with heart failure. Echocardiographic study showed a myxomatous-like mitral valve with posterior leaflet prolapse and severe regurgitation. Furthermore, he presented a prolapse of the septal and posterior leaflets of the tricuspid valve, also myxomatous-like. The second case is a 57-year-old man; acromegaly was diagnosed 14 years before the diagnosis of a severe aortic regurgitation, non-rheumatic-like. The patient was operated on with a mechanical valve replacement. One year later he suffered an endo*Corresponding author. Tel.: 134-96-593-8358; fax: 134-96-5937722. ´ E-mail address: [email protected] (F. Marın).
carditis by Staphylococcus epidermidis over the prosthesis, proceeding to valve replacement. The third case is a 57-year-old man, for whom acromegaly was diagnosed 9 months before the diagnosis of a moderate–severe aortic regurgitation without cardiac symptoms. Ventricular hypertrophy is unequivocally known in acromegaly (our patients had severe hypertrophy in echocardiographic studies). The high prevalence of hypertension, diabetes and hyperinsulinism in acromegalic patients casts doubt on the existence of an authentic acromegalic heart muscle disease, secondary to growth hormone excess. Nevertheless, it has been verified in experimental studies that growth Table 1 Patient characteristics
Valve disease Age (years) Sex Hypertension Diabetes LVEDD (mm) LVESD (mm) S (mm) PW (mm) Shortening fraction (%) LV mass (g / m 2 )
Case 1
Case 2
Case 3
Mitral regurgitation 58 Male Yes No 72 50 17 13 30 242
Aortic regurgitation 57 Male Yes Yes 77 56 26 23 27 464
Aortic regurgitation 57 Male No Yes 63 42 17 15 33 195
LVEDD, left ventricular end diastolic diameter; LVESD, left ventricular end systolic diameter; S, septum; PW, posterior wall; LV mass, left ventricular mass.
0167-5273 / 03 / $ – see front matter 2003 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/S0167-5273(02)00527-2
332
E. Paya´ et al. / International Journal of Cardiology 90 (2003) 331–332
hormone, by itself, or by its mediator, insulin-like growth factor-1, produces ventricular hypertrophy with an increase of myocite inotropism. Other factors which suggest the existence of acromegalic cardiomyopathy are the high prevalence of right ventricular diastolic dysfunction [3], and, after treatment with lanreotide, an analog of somatostatin, there is a significant decrease in cardiac mass. Interestingly, acromegalic ventricular hypertrophy develops in the absence of any afterload increase [2]. Growth hormone has been demonstrated to stimulate the accumulation of certain sulphated mucopolysaccharides, which would produce myxomatous degeneration of the valves. A report from an acromegalic patient with mitral regurgitation showed myxomatous degeneration of all four cardiac valves and cystic medial necrosis of the aorta and pulmonary artery [4]. A Japanese report described five surgical cases: one case of aortic and mitral regurgitation, one of aortic regurgitation, and three of mitral regurgitation [5]. Histopathologic examination of the excised valves revealed mucopolysaccharide deposits on the leaflets, and the myocardium showed fibrosis of interstitial spaces and endocardium, and disarrangement and enlargement of muscle fibers. However, a review of 27 autopsied cases of acromegaly [6] revealed that valve disease was present in five cases (19%): two aortic regurgitation, two mitral stenosis and regurgitation (none was rheumatic or luetic in origin) and one calcified stenosis and regurgitation secondary to old, healed, bacterial endocarditis.
We may add that the late diagnose of valve disease in our patients (and probably in acromegaly in general) may be related to the slow course of acromegalic disease, together with factors such as obesity, arthralgias, and fatigue, which reduce life activities, and retard the symptoms secondary to valve disease. Both experimental and clinical data support the existence of an acromegalic cardiomyopathy. The features of this disease would consist of myocardial hypertrophy, interstitial fibrosis, and cellular infiltration consistent with myocarditis. Furthermore, in accordance with these findings, we would add that valve disease due to excess growth hormone should be taken into account in cardiac evaluation of acromegalic patients.
References [1] Melmed S. Acromegaly. New Engl J Med 1990;322:966–77. [2] Sacca´ L, Cittadini A, Fazzio S. Growth hormone and the heart. Endocr Rev 1994;15:555–73. ´ F, Pico´ A, Martınez ´ [3] Marın JG et al. Biventricular impairment in diastolic function in acromegaly. Rev Esp Cardiol 2001;54:37–42. [4] Ondreyco SM, Lewis Jr. HD, Hartman CR. Myxomatous degeneration and cystic medial necrosis associated with acromegaly. Arch Intern Med 1980;140:547–9. [5] Ohtsuka G, Aomi S, Koyanagi H et al. Heart valve operation in acromegaly. Ann Thorac Surg 1997;64:390–3. [6] Lie JT, Grossman SJ. Pathology on the heart in acromegaly: anatomic findings in 27 autopsied patients. Am Heart J 1980;100:41–52.