Kansas Journal of 2011 An Unusual Cardiac Manifestation

An Unusual Cardiac Manifestation of Bassem Chehab, M.D., Mark Wiley, M.D., Peter Tadros, M.D. University of Kansas Medical Center Cardiovascular Research Institute; Cardiovascular Division Kansas City, KS

Introduction is a systemic or organ- multiple fat biopsies without any conclusive limited disease in which there is evidence of amyloidosis. Cardiac MRI also extracellular deposition of fibrils was performed and was non-conclusive for that gradually replace normal tissue in the diagnosis of cardiac amyloid. various organs in different pathological Meanwhile, she had worsening dyspnea and states, leading to loss of normal tissue interval increase in her architecture.1 The extent and location of size along with worsening tricuspid and amyloid deposition is directly responsible regurgitation. for the degree of cardiac failure.1,2 Her physical exam was positive for a 3/6 Usually 25% of the myocardium is systolic murmur at the level of the mitral replaced by amyloid deposition for valve radiating to the axillary region and symptoms to appear with congestive bilateral lower extremities edema. Chest x- failure being the most common presentation ray revealed only mild . Her of cardiac amyloidosis. In the clinical electrocardiogram obtained at rest is shown workup of patients with diastolic heart below in Figure 1. She underwent elective failure and myocardial hypertrophy, cardiac pericardiocentesis and pericardial fluid amyloidosis is an important differential analysis revealed only chronic inflammatory diagnosis. Once congestive pattern with modest improvement in her occurs, the median survival is less than six symptoms. She was started on diuretic months in untreated patients, and is the most with good response and significant common cause of death.2 improvement in her symptoms. She underwent a right heart catheterization and a Case Report right ventricular biopsy revealing a positive A 57-year-old female with a history of Congo red staining consistent with cardiac hypertension, diabetes mellitus, paroxysmal amyloidosis. atrial , morbid obesity, and multiple myeloma presented for recurrent Discussion episodes of shortness of air for the past six Cardiac amyloidosis is an invariably months. The initial echocardiogram revealed progressive infiltrative that normal left ventricular systolic function, carries a grave prognosis. Cardiac moderate tricuspid and mitral valve involvement may be present in up to one- regurgitation, severe diastolic dysfunction, third of patients with primary amyloidosis and a “speckled-like" pattern suggestive of (designated AL) resulting from possible amyloid disease. She underwent dyscrasias. 1,2 Although only 10% of the

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Figure 1. ECG revealing normal sinus rhythm with . Note the low voltage findings, anterior wall infarct (pseudo-infarct pattern), absent R wave in precordial leads, and possible inferior wall infarct. Artifacts noted in lead V6. patients with multiple myeloma develop systolic and abnormal diastolic function.2,4 systemic light-chain amyloid disease, their Cardiomegaly may be present on chest prognosis is very poor, especially in the roentgenography. The electrocardiogram presence of cardiac amyloidosis.3 most often reveals low QRS voltage, and Myocardial infiltration tends to be less with and abnormal axis are secondary amyloidosis (designated AA), in also common. A pattern of old anterior which the AA protein deposits tend to be may be simulated by smaller and more perivascular in location, diminutive or absent R waves in the right thus less likely to produce myocardial precordial leads, or by an old inferior dysfunction.2,4 Other forms include familial infarction by inferior Q-waves (pseudo- and senile amyloidosis.2 infarct pattern).2,6 Amyloid infiltration of The term amyloidosis means “starch- the atrium predisposes to , like.” The heart infiltrated with amyloid and ventricular are also appears tan and waxy and is rubbery in common. Atrioventricular conduction consistency. The atria also are enlarged defects are common and electro- significantly. Histologically, amyloid physiological testing is usually necessary to deposits can be detected with Congo red or detect significant intrahisian block. Sinus Sirius red staining and are present between node dysfunction is also common and the cardiac myocytes.2,5 ECG may show sick sinus syndrome.6 There are four overlapping syndromes is quite valuable and that may occur with cardiovascular reveals increased ventricular wall thickness involvement of amyloidosis, including with small intracavitary chambers, enlarged restrictive cardiomyopathy, systolic heart atria, and a thickened interatrial septum. failure, orthostatic , and The walls of the ventricles often reveal a presentation with conduction system distinctive appearance with a sparkling and disease. Most commonly, patients with granular texture, most likely resulting from cardiac amyloidosis present with signs of the amyloid deposition itself. Pericardial congestive heart failure with preserved effusions may be present, but usually do not

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advance to tamponade. Doppler echo- Approaches for patients with AL cardiography is valuable to evaluate amyloidosis involve chemotherapy with diastolic dysfunction, the degree of which alkylating agents alone or in combination offers prognostic information.3,6,7 Cardiac with autologous bone marrow stem cell MRI has a very high sensitivity for the transplantation and heart transplantation.2,11 detection of cardiac amyloid, and also may In terms of conventional cardiac be valuable in measuring the extent of medications, the use of digitalis glycosides amyloid deposition in the heart, a significant requires additional vigilance because prognostic factor.8,9 patients with cardiac amyloidosis have The diagnosis of cardiac amyloidosis increased sensitivity to digitalis can be ascertained by either: (1) a positive preparations. Calcium-channel antagonists biopsy from a noncardiac tissue in addition also require caution because their negative to sonographic evidence of amyloidosis, inotropic effect has the potential to which includes a mean left ventricular wall exacerbate heart failure. Pacemakers are thickness of greater than 12 mm in the frequently indicated for conduction system absence of other causes of LV hypertrophy, disturbances, and implantable cardioverter- or (2) an illustrating defibrillators may be considered. The amyloid deposition in addition to laboratory mainstay of symptom relief in volume and clinical evidence of organ involvement. overloaded patients is the judicious use of In patients with cardiac involvement, diuretics, which requires very careful endomyocardial biopsy is a relatively safe titration, in combination with rigorous fluid procedure in experienced hands with 100% restriction.10 sensitivity in diagnosis of cardiac amyloidosis. Biopsy specimen from the Conclusion involved organ, such as the heart or from the In summary, cardiac amyloidosis is a abdominal fat pad, exhibits a red or pink progressively infiltrative cardiomyopathy color under light microscopy after chemical that should be suspected in patients with staining with Congo red and a dramatic multiple myeloma and worsening dyspnea. apple-green birefringence under polarized It carries a poor prognosis even with light.2,5,6 aggressive therapy. A cardiac screening in Patients with cardiac amyloidosis have all patients with multiple myeloma should few treatment options, although there are include at least an electrocardiogram and ongoing attempts to modify the severe complete cardiac sonography. natural history of this disorder.10

References 1 Gertz MA, Comenzo R, Falk RH, et al. 2 Falk RH. Diagnosis and management of Definition of organ involvement and the cardiac amyloidoses. Circulation 2005; treatment response in immunoglobulin 112(13):2047-2060. light chain amyloidosis (AL): A consensus 3 Dubrey SW, Cha K, Skinner M, LaValley opinion from the 10th International M, Falk RH. Familial and primary (AL) Symposium on Amyloid and Amyloidosis, cardiac amyloidosis: Echocardio- Tours, France, 18-22 April 2004 . Am J graphically similar diseases with distinctly Hematol 2005; 79(4):319-328. different clinical outcomes. Heart 1997; 78(1):74-82.

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4 Kyle RA, Gertz MA. Primary systemic 9 Kusunose K, Yamada H, Iwase T, et al. amyloidosis: Clinical and laboratory Images in cardiovascular medicine. features in 474 cases. Semin Hematol Cardiac magnetic resonance imaging and 1995; 32(1):45-59. 2-dimensional speckle tracking 5 Pellikka PA, Holmes DR Jr, Edwards WD, echocardiography in secondary cardiac Nishimura RA, Tajik AJ, Kyle RA. amyloidosis. Circ J 2010; 74(7):1494- Endomyocardial biopsy in 30 patients with 1496. primary amyloidosis and suspected cardiac 10 Parikh S, de Lemos JA. Current involvement. Arch Intern Med 1988; therapeutic strategies in cardiac 148(3):662-666. amyloidosis. Curr Treat Options 6 Rahman JE, Helou EF, Gelzer-Bell R, et Cardiovasc Med 2005; 7(6):443-448. al. Noninvasive diagnosis of biopsy- 11 Seldin DC, Anderson JJ, Sanchorawala V, proven cardiac amyloidosis. J Am Coll et al. Improvement in quality of life of Cardiol 2004; 43(3):410-415. patients with AL amyloidosis treated with 7 Devereux RB, Alonso DR, Lutas EM, et high-dose and autologous stem al. Echocardiographic assessment of left cell transplantation. Blood 2004; : Comparison to 104(6):1888-1893. necropsy findings. Am J Cardiol 1986; 57(6):450-458. Keywords: , multiple 8 Vogelsberg H, Mahrholdt H, Deluigi CC, myeloma, amyloidosis, et al. Cardiovascular magnetic resonance in clinically suspected cardiac amyloidosis: Noninvasive imaging compared to endomyocardial biopsy. J Am Coll Cardiol 2008; 51(10): p. 1022- 1030.

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