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Double Cardiomyopathy: Coexistent Cardiac Amyloidosis and Hypertrophic Obstructive Cardiomyopathy
Double Cardiomyopathy: Coexistent Cardiac Amyloidosis and Hypertrophic Obstructive Cardiomyopathy William P. Buchanan, MD, Steven W. Schreiter, MD, Frederic R. Kahl, MD, Patrick E. Lantz, MD, Herman B. Cheek, MD, John Risley, BS, and Abdel-Mohsen Nomeir, MD, Winston-Salem, North Carolina
A combination of hypertrophic obstructive cardiomyopathy (HOCM) and cardiac amyloidosis in the same patient is very rare. Clinical diagnosis could be extremely difficult and may require myocardial biopsy. We are reporting a patient with this combination who was referred to our institution because of features of HOCM based on clinical, echocardiographic and Doppler criteria. Cardiac amyloidosis was only recognized after myocardial biopsy that failed to reveal evidence of HOCM. Only after the patient expired from severe, intractable heart failure did the autopsy findings confirm the association of HOCM. We believe that the combination of the two cardiomyopathic processes is very rare and makes treatment extremely difficult. ( J AM Soc EcHOCARDIOGR 1993;6:87-90.)
An unusual and rare feature of cardiac amyloidosis is the ability of this disease to present with features of hypertrophic obstructive cardiomyopathy (HOCM) .1 The combination of systolic anterior motion of the mitral valve (MV) leaflet and left ventricular outflow tract (LVOT) obstruction has been previously reported in patients with cardiac amyloidosis simulating HOCM. 2 The association of cardiac amyloidosis and hypertrophic cardiomyopathy in the same patient is extremely rare. A literature search revealed one case report in the English literature.3 We present a patient with terminal heart failure and pathologic evidence of both HOCM and cardiac amyloidosis.
CASE HISTORY
H.W. was a 72-year-old white woman with progressive dyspnea at rest, anorexia, 65-pound weight loss over 6 months, and a recurrent transudative right pleural effusion. Her blood pressure was 78 I 48 mm Hg with a pulse of l 00 beats I min and orthostatic changes on sitting upright. Carotid upstroke was brisk and slightly bifid to palpation. Bilateral cervical, axillary, and inguinal adenopathy was present. There was dullness to percussion at both lung bases. There was an apical S4 gallop and a harsh grade 3 I 6 hoFrom the Department of Medicine, Section on Cardiology, and the Department of Pathology, The Bowman Gray School ofMed· icine, Wake Forest University. Reprint requests: Abdel-Mohsen Nomeir, MD, Department of Medicine, Section on Cardiology, Bowman Gray School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157. Copyright© 1993 by the American Society ofEchocardiography. 0894-7317/93$1.00 + .10 27/l/42016
Figure 1 Parasternal orientation of two-dimensional echocardiogram in diastolic frame (A) and pathologic correlate (B) demonstrating asymmetric septal hypertrophy, small left ventricular chamber size, papillary muscle hypertrophy, a narrow left ventricular outflow tract, and a prominent subaortic shelf. IVS, Interventricular septum; PM, papillary muscle; PLVW, posterior left ventricular wall; L VOT, left ventricular outflow tract; LA, left atrium; Ao, aorta; R V, right ventricle; PLE, pleural effusion. 87
88
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Figure 2 Left ventricular pressure tracing during catheter pullback from the apex to the left ventricular outflow tract demonstrating an intraventricular pressure gradient.
losystolic murmur heard best along the left sternal border without radiation to the carotids. The murmur had postextrasystolic accentuation and it also increased in intensity with V alsalva maneuver and decreased with leg raising. There was 2 + pitting bipedal edema. LABORATORY DATA
Chest x-ray film showed evidence of pulmonary edema and cardiomegaly. An electrocardiogram demonstrated normal sinus rhythm with left ventricular hypertrophy. An echocardiogram (Figure 1, A) demonstrated a small left ventricular chamber, asymmetric septal hypertrophy, systolic anterior motion
of the MV leaflet, and moderate mitral regurgitation. The Doppler evaluation was technically difficult but did demonstrate at least a 30 mm Hg LVOT gradient at rest. The interventricular septum measured 29 mm and the posterior left ventricular wall thickness was 18 mm by M-mode echocardiography. Right and left heart catheterization revealed slightly elevated right and left diastolic pressures. Pullback from the left ventricular apex to the outflow tract demonstrated an unprovoked peak resting systolic gradient of 57 mm Hg (Figure 2). Coronary angiography showed nonobstructive coronary artery disease. Biplane left ventriculography revealed a small left ventricular chamber with heavy trabeculations and an ejection fraction of 81%. There was 3 + mitral regurgitation and systolic anterior motion of the anterior MV
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Figure 3 Photomicrograph s of the heart at autopsy. Extensive myofibril disarray is present (A). Perivascular amyloid infiltration is demonstrated by Congo red staining (B) and yellowgreen birefringence under polarized light (C).
leaflet. Rectal and inguinal node biopsies revealed extensive amyloid infiltration. Serum and urine were negative for monoclonal proteins. The results of the nodal biopsies prompted an endomyocardial biopsy of the right ventricular septum that also revealed infiltration of the myocardium with amyloid but no pathologic evidence of hypertrophic cardiomyopathy. HOSPITAL COURSE
During her hospitalization, the patient did not tolerate calcium channel blocker, j3-blocker, disopyramide, or digitalis therapy. Despite manipulations in her volume status, the patient's heart failure worsened. She expired from severe pulmonary edema and respiratory failure l month after her admission to our institution. Autopsy revealed an enlarged heart that weighed 630 gm. The coronary arteries did not contain significant atherosclerosis. There was massive asynunetric septal hypertrophy with the septum measuring 31 mm and the left ventricular free wall measuring 20 mm (Figure l, B). Microscopic examination of the heart revealed extensive septal myocardial
fibril disarray compatible with hypertrophic cardiomyopathy (Figure 3, A). A diffuse perivascular amyloid infiltration was seen with Congo red staining (Figure 3, B) and was confirmed by the presence of typical yellow-green birefringence when viewed under polarized light (Figure 3, C). Autopsy also confirmed the presence of amyloid infiltration involving other organ systems and an atypicallymphoproliferative process involving pericaval lymph nodes and rectosigmoid soft tissue. Immunohistochemical classification on the postmortem tissue was not possible. DISCUSSION
The combination of cardiac amyloidosis and HOCM in the same patient is evidently very rare, with only 3 one previous case report in the English literature. Findings that support the diagnosis of HOCM in our patient include the patient's physical findings, left ventricular hypertrophy on electrocardiogram, asymmetric septal hypertrophy, a resting L VOT gradient, systolic anterior motion of the anterior MV leaflet and, finally, diffuse septal myofibril disarray at
Journal of the American Society of Echocardiography January-February 1993
90 Buchanan et al.
autopsy. 4 Features supporting the diagnosis of cardiac amyloidosis in our patient include the presence of orthostatic hypotension, positive Congo red staining, and yellow-green birefringence of the myocardium seen under polarized light, and documented pathologic features of systemic amyloidosis. The clinical and pathologic documentation of both cardiac amyloidosis and HOCM is consistent with a true double cardiomyopathy. This patient's progressive heart failure and pulmonary edema were believed to be the result of severe diastolic dysfunction that can occur in either type of cardiomyopathy. Accurate antemortem diagnosis of the combination of both disease processes would have been impossible without appropriate pathologic confirmation. The echocardiographic and cardiac catheterization data were more consistent with HOCM and, therefore, amyloid involvement of the heart was initially not entertained. However, a recent report in the literature does indicate that up to 8% of cases of cardiac amyloidosis have echocardiographic features mimicking HOCM. 2 Endomyocardial biopsy confirmed cardiac amyloid deposition but did not demonstrate any pathologic features of HOCM. Effective treatment of this "double cardiomyopathy'' would be expected to be difficult. The usefulness of negative inotropic agents in HOCM is well established. However, there are reports of worsening heart failure and deterioration in patients with cardiac amyloidosis treated with calcium channel blockers, and indeed our patient did not tolerate verapamil nor disopyramide
despite overall good left ventricular systolic performance.5 In conclusion, this is a very interesting case of a double cardiomyopathy resulting in severe and medically uncontrolled left ventricular diastolic dysfunction. This case supports the use of endomyocardial biopsy to confirm cardiac amyloidosis if clinically suspected. However, the antemortem diagnosis of both HOCM and cardiac amyloidosis does not appear to be possible and requires detailed pathologic examination of the heart.
REFERENCES l. Weston LT, Raybuck BD, Rabinowitz M, Brinker JA, Oetgen WJ. Primary amyloid heart disease presenting as hypertrophic obstructive cardiomyopathy. Cathet Cardiovasc Diagn 1986;12:176-81. 2. Foley DA, Tajik AJ, Seward JB, Oh JK, Gertz MA, Kyle RA. Cardiac amyloidosis mimicking hypertrophic cardiomyopathy: a lirtle known entity. Circulation 1991;84:1!-630. 3. Daniels RA, Weinberg R, Rangwala AF, Mintz G. Cardiac amyloidosis and idiopathic hypertrophic subaortic stenosis. Journal of the Medical Society of New Jersey 1984;81:481-4. 4. Marion BJ, Epstein SE. Hypertrophic cardiomyopathy. Recent observations regarding the specificity of three hallmarks of the disease: asymmetric septal hypertrophy, septal disorganization and systolic anterior motion of the anterior mitral leaflet. Am J Cardiol1980;45:141-54. 5. Gertz MA, Falk RH, Skinner M, Cohen AS, Kyle RA. Wors· ening of congestive heart failure in amyloid heart disease treated by calcium channel-blocking agents. Am J Cardia! 1985;55:1645.
A combination of hypertrophic obstructive cardiomyopathy (HOCM) and cardiac amyloidosis in the same patient is very rare. Clinical diagnosis could be extremely difficult and may require myocardial biopsy. We are reporting a patient with this combination who was referred to our institution because of features of HOCM based on clinical, echocardiographic and Doppler criteria. Cardiac amyloidosis was only recognized after myocardial biopsy that failed to reveal evidence of HOCM. Only after the patient expired from severe, intractable heart failure did the autopsy findings confirm the association of HOCM. We believe that the combination of the two cardiomyopathic processes is very rare and makes treatment extremely difficult. ( J AM Soc EcHOCARDIOGR 1993;6:87-90.)
An unusual and rare feature of cardiac amyloidosis is the ability of this disease to present with features of hypertrophic obstructive cardiomyopathy (HOCM) .1 The combination of systolic anterior motion of the mitral valve (MV) leaflet and left ventricular outflow tract (LVOT) obstruction has been previously reported in patients with cardiac amyloidosis simulating HOCM. 2 The association of cardiac amyloidosis and hypertrophic cardiomyopathy in the same patient is extremely rare. A literature search revealed one case report in the English literature.3 We present a patient with terminal heart failure and pathologic evidence of both HOCM and cardiac amyloidosis.
CASE HISTORY
H.W. was a 72-year-old white woman with progressive dyspnea at rest, anorexia, 65-pound weight loss over 6 months, and a recurrent transudative right pleural effusion. Her blood pressure was 78 I 48 mm Hg with a pulse of l 00 beats I min and orthostatic changes on sitting upright. Carotid upstroke was brisk and slightly bifid to palpation. Bilateral cervical, axillary, and inguinal adenopathy was present. There was dullness to percussion at both lung bases. There was an apical S4 gallop and a harsh grade 3 I 6 hoFrom the Department of Medicine, Section on Cardiology, and the Department of Pathology, The Bowman Gray School ofMed· icine, Wake Forest University. Reprint requests: Abdel-Mohsen Nomeir, MD, Department of Medicine, Section on Cardiology, Bowman Gray School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157. Copyright© 1993 by the American Society ofEchocardiography. 0894-7317/93$1.00 + .10 27/l/42016
Figure 1 Parasternal orientation of two-dimensional echocardiogram in diastolic frame (A) and pathologic correlate (B) demonstrating asymmetric septal hypertrophy, small left ventricular chamber size, papillary muscle hypertrophy, a narrow left ventricular outflow tract, and a prominent subaortic shelf. IVS, Interventricular septum; PM, papillary muscle; PLVW, posterior left ventricular wall; L VOT, left ventricular outflow tract; LA, left atrium; Ao, aorta; R V, right ventricle; PLE, pleural effusion. 87
88
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Figure 2 Left ventricular pressure tracing during catheter pullback from the apex to the left ventricular outflow tract demonstrating an intraventricular pressure gradient.
losystolic murmur heard best along the left sternal border without radiation to the carotids. The murmur had postextrasystolic accentuation and it also increased in intensity with V alsalva maneuver and decreased with leg raising. There was 2 + pitting bipedal edema. LABORATORY DATA
Chest x-ray film showed evidence of pulmonary edema and cardiomegaly. An electrocardiogram demonstrated normal sinus rhythm with left ventricular hypertrophy. An echocardiogram (Figure 1, A) demonstrated a small left ventricular chamber, asymmetric septal hypertrophy, systolic anterior motion
of the MV leaflet, and moderate mitral regurgitation. The Doppler evaluation was technically difficult but did demonstrate at least a 30 mm Hg LVOT gradient at rest. The interventricular septum measured 29 mm and the posterior left ventricular wall thickness was 18 mm by M-mode echocardiography. Right and left heart catheterization revealed slightly elevated right and left diastolic pressures. Pullback from the left ventricular apex to the outflow tract demonstrated an unprovoked peak resting systolic gradient of 57 mm Hg (Figure 2). Coronary angiography showed nonobstructive coronary artery disease. Biplane left ventriculography revealed a small left ventricular chamber with heavy trabeculations and an ejection fraction of 81%. There was 3 + mitral regurgitation and systolic anterior motion of the anterior MV
Journal of the American Society of Echocardiography Volume 6, Nwnber l
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Figure 3 Photomicrograph s of the heart at autopsy. Extensive myofibril disarray is present (A). Perivascular amyloid infiltration is demonstrated by Congo red staining (B) and yellowgreen birefringence under polarized light (C).
leaflet. Rectal and inguinal node biopsies revealed extensive amyloid infiltration. Serum and urine were negative for monoclonal proteins. The results of the nodal biopsies prompted an endomyocardial biopsy of the right ventricular septum that also revealed infiltration of the myocardium with amyloid but no pathologic evidence of hypertrophic cardiomyopathy. HOSPITAL COURSE
During her hospitalization, the patient did not tolerate calcium channel blocker, j3-blocker, disopyramide, or digitalis therapy. Despite manipulations in her volume status, the patient's heart failure worsened. She expired from severe pulmonary edema and respiratory failure l month after her admission to our institution. Autopsy revealed an enlarged heart that weighed 630 gm. The coronary arteries did not contain significant atherosclerosis. There was massive asynunetric septal hypertrophy with the septum measuring 31 mm and the left ventricular free wall measuring 20 mm (Figure l, B). Microscopic examination of the heart revealed extensive septal myocardial
fibril disarray compatible with hypertrophic cardiomyopathy (Figure 3, A). A diffuse perivascular amyloid infiltration was seen with Congo red staining (Figure 3, B) and was confirmed by the presence of typical yellow-green birefringence when viewed under polarized light (Figure 3, C). Autopsy also confirmed the presence of amyloid infiltration involving other organ systems and an atypicallymphoproliferative process involving pericaval lymph nodes and rectosigmoid soft tissue. Immunohistochemical classification on the postmortem tissue was not possible. DISCUSSION
The combination of cardiac amyloidosis and HOCM in the same patient is evidently very rare, with only 3 one previous case report in the English literature. Findings that support the diagnosis of HOCM in our patient include the patient's physical findings, left ventricular hypertrophy on electrocardiogram, asymmetric septal hypertrophy, a resting L VOT gradient, systolic anterior motion of the anterior MV leaflet and, finally, diffuse septal myofibril disarray at
Journal of the American Society of Echocardiography January-February 1993
90 Buchanan et al.
autopsy. 4 Features supporting the diagnosis of cardiac amyloidosis in our patient include the presence of orthostatic hypotension, positive Congo red staining, and yellow-green birefringence of the myocardium seen under polarized light, and documented pathologic features of systemic amyloidosis. The clinical and pathologic documentation of both cardiac amyloidosis and HOCM is consistent with a true double cardiomyopathy. This patient's progressive heart failure and pulmonary edema were believed to be the result of severe diastolic dysfunction that can occur in either type of cardiomyopathy. Accurate antemortem diagnosis of the combination of both disease processes would have been impossible without appropriate pathologic confirmation. The echocardiographic and cardiac catheterization data were more consistent with HOCM and, therefore, amyloid involvement of the heart was initially not entertained. However, a recent report in the literature does indicate that up to 8% of cases of cardiac amyloidosis have echocardiographic features mimicking HOCM. 2 Endomyocardial biopsy confirmed cardiac amyloid deposition but did not demonstrate any pathologic features of HOCM. Effective treatment of this "double cardiomyopathy'' would be expected to be difficult. The usefulness of negative inotropic agents in HOCM is well established. However, there are reports of worsening heart failure and deterioration in patients with cardiac amyloidosis treated with calcium channel blockers, and indeed our patient did not tolerate verapamil nor disopyramide
despite overall good left ventricular systolic performance.5 In conclusion, this is a very interesting case of a double cardiomyopathy resulting in severe and medically uncontrolled left ventricular diastolic dysfunction. This case supports the use of endomyocardial biopsy to confirm cardiac amyloidosis if clinically suspected. However, the antemortem diagnosis of both HOCM and cardiac amyloidosis does not appear to be possible and requires detailed pathologic examination of the heart.
REFERENCES l. Weston LT, Raybuck BD, Rabinowitz M, Brinker JA, Oetgen WJ. Primary amyloid heart disease presenting as hypertrophic obstructive cardiomyopathy. Cathet Cardiovasc Diagn 1986;12:176-81. 2. Foley DA, Tajik AJ, Seward JB, Oh JK, Gertz MA, Kyle RA. Cardiac amyloidosis mimicking hypertrophic cardiomyopathy: a lirtle known entity. Circulation 1991;84:1!-630. 3. Daniels RA, Weinberg R, Rangwala AF, Mintz G. Cardiac amyloidosis and idiopathic hypertrophic subaortic stenosis. Journal of the Medical Society of New Jersey 1984;81:481-4. 4. Marion BJ, Epstein SE. Hypertrophic cardiomyopathy. Recent observations regarding the specificity of three hallmarks of the disease: asymmetric septal hypertrophy, septal disorganization and systolic anterior motion of the anterior mitral leaflet. Am J Cardiol1980;45:141-54. 5. Gertz MA, Falk RH, Skinner M, Cohen AS, Kyle RA. Wors· ening of congestive heart failure in amyloid heart disease treated by calcium channel-blocking agents. Am J Cardia! 1985;55:1645.