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Amyloid cardiomyopathy presenting as persistent symptomatic pleural effusions
ARTICLE IN PRESS Respiratory Medicine Extra (2005) 1, 79–80
respiratory MEDICINE Extra
CASE REPORT
Amyloid cardiomyopathy presenting as persistent symptomatic pleural effusions Zoe Daniil, Epaminondas Zakynthinos, Evangelia Papageorgiou, Maria Loannou, Konstantinos Kostikas, Konstantinos Gourgoulianis Department of Respiratory Medicine, University of Thessaly, University Hospital of Larissa, Mezourlo, 41110 Larissa, Greece Received 18 May 2005
KEYWORDS Pleural effusion; Amyloidosis; Cardiomyopathy
Summary A 73-year-old male presented with dyspnea and bilateral transudative pleural effusions that persisted despite aggressive diuresis. No etiology had been established despite an extensive workout. The only abnormal finding was diastolic dysfunction documented in an echocardiographic study. This raised the possibility of amyloid infiltrative cardiomyopathy. The diagnosis was supported by the findings of right cardiac catheterization and established by abdominal fat biopsy. The presence of systemic amyloidosis with myocardial infiltration should be ruled out in any patient with otherwise unexplained transudative pleural effusions and evidence of diastolic heart dysfunction. & 2005 Elsevier Ltd. All rights reserved.
Case history A 74-year-old male, never smoker, was referred for evaluation of dyspnea. He had a five-year history of hypertension treated with a calcium channel blocker. Over the last year he had been hospitalized twice for a right-sided transudative pleural effusion. No etiology had been established despite an extensive workout and only a slight improvement had been achieved with aggressive diuresis. The patient’s routine laboratory tests were normal. The chest X-ray and computed tomography scan revealed bilateral pleural effusions. The ECG showed Corresponding author. Tel.: +302410682898.
E-mail address: [email protected] (Z. Daniil).
nonspecific abnormalities. Bilateral thoracenteses revealed transudative pleural effusions. Transthoracic echocardiogram showed mild left atrial dilation, mild concentric left ventricular hypertrophy predominantly in the interventricular septum, with normal systolic function. Right heart function was normal. Pulmonary artery systolic pressure was 45 mmHg. Diagnostic right heart catheterization was performed and elevated central venous pressure (14 mmHg), systolic and diastolic pulmonary artery pressure (46/26 mmHg), right ventricular end-diastolic pressure (14 mmHg), and pulmonary capillary wedge pressure (22 mmHg) were found. The patient’s echocardiographic study documented diastolic dysfunction, a finding that could be consistent with his history of hypertension
1744-9049/$ - see front matter & 2005 Elsevier Ltd. All rights reserved. doi:10.1016/j.rmedx.2005.05.005
ARTICLE IN PRESS 80
Figure 1 Congo red staining of the abdominal fat biopsy (original magnification 40 10).
and advanced age. However, hypertension alone could not explain the patient’s symptoms and the chronic pleural effusion. Surprisingly, the data obtained during cardiac catheterization were interpreted as evidence of heart failure. Additionally, serum brain natriuretic peptide levels were elevated (571 pg/ml, normal range: 0–100). The mild thickening of the interventricular septum combined with the above findings raised the possibility of amyloid infiltrative cardiomyopathy, a disease that characteristically results in diastolic dysfunction.1 Diastolic dysfunction can raise filling pressures and induce pleural effusion. An abdominal fat biopsy revealed minimal, band-like deposition adjacent to the basement membrane of the sweat gland tubules which appeared apple-green birefringence after Congo red staining and examination under polarized light; this finding confirmed the diagnosis of systemic amyloidosis2 (Fig. 1). The patient was treated with melphalan and prednisolone without any improvement. Six months later he developed bladder amyloidosis that was proven histologically. Amyloid cardiomyopathy is defined pathologically by the deposition of amyloid in the myocardium and clinically by signs of myocardial or conduction system dysfunction.3,4 These abnormalities can be detected with a number of commonly used tests.5 The most common ECG abnormality is low voltage in the limb and chest leads, occurring in over 50% of patients. Diastolic dysfunction is the most common and earliest echocardiographic abnormality in cardiac amyloidosis.6 Right ventricular diastolic dysfunction, symmetric left ventricular wall thickening or asymmetric septal involvement
Z. Daniil et al. can also be demonstrated. The most distinctive echocardiographic finding is a granular, ‘‘sparkling’’ appearance of the myocardium, resulting from the presence of amyloid and collagen nodules in the heart.7 Myocardial biopsies frequently demonstrate amyloid deposits in systemic amyloidosis and suspected cardiac involvement but the indications for endomyocardial biopsy are not well defined and should be performed when positive findings will clearly alter clinical management.8 Pleural effusions have not been extensively studied in systemic amyloidosis. Amyloid pleural transudative effusions may persist despite aggressive diuresis and drainage. Amyloid-induced cardiomyopathy often accompanies pleural effusions, suggesting that effusions may be primarily a consequence of ventricular dysfunction. Low oncotic pressure resulting from amyloidosis-related nephrotic syndrome represents another mechanism, which was not proven in our patient. Amyloid infiltration of the pleura plays also a central role in the creation and persistence of pleural effusions, which, however, are exudative.1 The presence of systemic amyloidosis with myocardial infiltration should be ruled out in any patient with otherwise unexplained transudative pleural effusions and evidence of diastolic heart dysfunction.
References 1. Berk JL, Keane J, Seldin DC, et al. Persistent pleural effusions in primary systemic amyloidosis. Chest 2003;124: 969–77. 2. Gillmore JD, Hawkins PN. Amyloidosis and the respiratory tract. Thorax 1999;54(5):444–51. 3. Swanton RH, Brooksby IA, Davies MJ, Coltart DJ, Jenkins BS, Webb-Peploe MM. Systolic and diastolic ventricular function in cardiac amyloidosis. Studies in six cases diagnosed with endomyocardial biopsy. Am J Cardiol 1977;39: 658–64. 4. Chew C, Ziady GM, Raphael MJ, Oacley CM. The functional defect in amyloid heart disease. The ‘‘stiff heart’’ syndrome. Am J Cardiol 1975;36:438–44. 5. Falk RA, Comenzo RL, Skinner M. The systemic amyloidosis. N Engl J Med 1997;337:898–909. 6. Rahman JE, Helou EF, Gelzer-Bell R, et al. Noninvasive diagnosis of biopsy-proven cardiac amyloidosis. J Am Coll Cardiol 2004;43:410–5. 7. Siqueira-Filho AG, Cunha CL, Tajik AJ, Seward TT. M-mode and two-dimensional echocardiographic features in cardiac amyloidosis. Circulation 1981;63:188–96. 8. Tyberg TI, Goodyer AV, Hurst III VW, Alexander J, Langou RA. Left ventricular filling in differentiating restrictive amyloid cardiomyopathy and constrictive pericarditis. Am J Cardiol 1981;47:791–8.
respiratory MEDICINE Extra
CASE REPORT
Amyloid cardiomyopathy presenting as persistent symptomatic pleural effusions Zoe Daniil, Epaminondas Zakynthinos, Evangelia Papageorgiou, Maria Loannou, Konstantinos Kostikas, Konstantinos Gourgoulianis Department of Respiratory Medicine, University of Thessaly, University Hospital of Larissa, Mezourlo, 41110 Larissa, Greece Received 18 May 2005
KEYWORDS Pleural effusion; Amyloidosis; Cardiomyopathy
Summary A 73-year-old male presented with dyspnea and bilateral transudative pleural effusions that persisted despite aggressive diuresis. No etiology had been established despite an extensive workout. The only abnormal finding was diastolic dysfunction documented in an echocardiographic study. This raised the possibility of amyloid infiltrative cardiomyopathy. The diagnosis was supported by the findings of right cardiac catheterization and established by abdominal fat biopsy. The presence of systemic amyloidosis with myocardial infiltration should be ruled out in any patient with otherwise unexplained transudative pleural effusions and evidence of diastolic heart dysfunction. & 2005 Elsevier Ltd. All rights reserved.
Case history A 74-year-old male, never smoker, was referred for evaluation of dyspnea. He had a five-year history of hypertension treated with a calcium channel blocker. Over the last year he had been hospitalized twice for a right-sided transudative pleural effusion. No etiology had been established despite an extensive workout and only a slight improvement had been achieved with aggressive diuresis. The patient’s routine laboratory tests were normal. The chest X-ray and computed tomography scan revealed bilateral pleural effusions. The ECG showed Corresponding author. Tel.: +302410682898.
E-mail address: [email protected] (Z. Daniil).
nonspecific abnormalities. Bilateral thoracenteses revealed transudative pleural effusions. Transthoracic echocardiogram showed mild left atrial dilation, mild concentric left ventricular hypertrophy predominantly in the interventricular septum, with normal systolic function. Right heart function was normal. Pulmonary artery systolic pressure was 45 mmHg. Diagnostic right heart catheterization was performed and elevated central venous pressure (14 mmHg), systolic and diastolic pulmonary artery pressure (46/26 mmHg), right ventricular end-diastolic pressure (14 mmHg), and pulmonary capillary wedge pressure (22 mmHg) were found. The patient’s echocardiographic study documented diastolic dysfunction, a finding that could be consistent with his history of hypertension
1744-9049/$ - see front matter & 2005 Elsevier Ltd. All rights reserved. doi:10.1016/j.rmedx.2005.05.005
ARTICLE IN PRESS 80
Figure 1 Congo red staining of the abdominal fat biopsy (original magnification 40 10).
and advanced age. However, hypertension alone could not explain the patient’s symptoms and the chronic pleural effusion. Surprisingly, the data obtained during cardiac catheterization were interpreted as evidence of heart failure. Additionally, serum brain natriuretic peptide levels were elevated (571 pg/ml, normal range: 0–100). The mild thickening of the interventricular septum combined with the above findings raised the possibility of amyloid infiltrative cardiomyopathy, a disease that characteristically results in diastolic dysfunction.1 Diastolic dysfunction can raise filling pressures and induce pleural effusion. An abdominal fat biopsy revealed minimal, band-like deposition adjacent to the basement membrane of the sweat gland tubules which appeared apple-green birefringence after Congo red staining and examination under polarized light; this finding confirmed the diagnosis of systemic amyloidosis2 (Fig. 1). The patient was treated with melphalan and prednisolone without any improvement. Six months later he developed bladder amyloidosis that was proven histologically. Amyloid cardiomyopathy is defined pathologically by the deposition of amyloid in the myocardium and clinically by signs of myocardial or conduction system dysfunction.3,4 These abnormalities can be detected with a number of commonly used tests.5 The most common ECG abnormality is low voltage in the limb and chest leads, occurring in over 50% of patients. Diastolic dysfunction is the most common and earliest echocardiographic abnormality in cardiac amyloidosis.6 Right ventricular diastolic dysfunction, symmetric left ventricular wall thickening or asymmetric septal involvement
Z. Daniil et al. can also be demonstrated. The most distinctive echocardiographic finding is a granular, ‘‘sparkling’’ appearance of the myocardium, resulting from the presence of amyloid and collagen nodules in the heart.7 Myocardial biopsies frequently demonstrate amyloid deposits in systemic amyloidosis and suspected cardiac involvement but the indications for endomyocardial biopsy are not well defined and should be performed when positive findings will clearly alter clinical management.8 Pleural effusions have not been extensively studied in systemic amyloidosis. Amyloid pleural transudative effusions may persist despite aggressive diuresis and drainage. Amyloid-induced cardiomyopathy often accompanies pleural effusions, suggesting that effusions may be primarily a consequence of ventricular dysfunction. Low oncotic pressure resulting from amyloidosis-related nephrotic syndrome represents another mechanism, which was not proven in our patient. Amyloid infiltration of the pleura plays also a central role in the creation and persistence of pleural effusions, which, however, are exudative.1 The presence of systemic amyloidosis with myocardial infiltration should be ruled out in any patient with otherwise unexplained transudative pleural effusions and evidence of diastolic heart dysfunction.
References 1. Berk JL, Keane J, Seldin DC, et al. Persistent pleural effusions in primary systemic amyloidosis. Chest 2003;124: 969–77. 2. Gillmore JD, Hawkins PN. Amyloidosis and the respiratory tract. Thorax 1999;54(5):444–51. 3. Swanton RH, Brooksby IA, Davies MJ, Coltart DJ, Jenkins BS, Webb-Peploe MM. Systolic and diastolic ventricular function in cardiac amyloidosis. Studies in six cases diagnosed with endomyocardial biopsy. Am J Cardiol 1977;39: 658–64. 4. Chew C, Ziady GM, Raphael MJ, Oacley CM. The functional defect in amyloid heart disease. The ‘‘stiff heart’’ syndrome. Am J Cardiol 1975;36:438–44. 5. Falk RA, Comenzo RL, Skinner M. The systemic amyloidosis. N Engl J Med 1997;337:898–909. 6. Rahman JE, Helou EF, Gelzer-Bell R, et al. Noninvasive diagnosis of biopsy-proven cardiac amyloidosis. J Am Coll Cardiol 2004;43:410–5. 7. Siqueira-Filho AG, Cunha CL, Tajik AJ, Seward TT. M-mode and two-dimensional echocardiographic features in cardiac amyloidosis. Circulation 1981;63:188–96. 8. Tyberg TI, Goodyer AV, Hurst III VW, Alexander J, Langou RA. Left ventricular filling in differentiating restrictive amyloid cardiomyopathy and constrictive pericarditis. Am J Cardiol 1981;47:791–8.