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44-Year-Old Man With Exertional Dyspnea, Weight Loss, and Palpitations

      A 44-year-old man presented for evaluation of progressive fatigue, dyspnea on exertion, and weight loss. He was previously healthy and was an avid runner until the onset of his symptoms 4 months earlier. He noticed frequent palpitations and had an episode of exertional syncope several days before evaluation. He also described musculoskeletal pain in his back and lower extremities. His appetite was poor, and he reported a 9-kg unintentional weight loss over 3 months. The patient had no history of alcohol, tobacco, or illicit drug use, and his family history was unremarkable.
      On physical examination, the patient was afebrile, his pulse rate was regular at 56 beats/min, and his seated blood pressure was 95/59 mm Hg. He appeared fatigued but in no apparent distress. Neither rashes nor palpable lymphadenopathy was present. His neck was supple, and there was no evidence of jugular venous distention. Cardiac examination revealed frequent pauses and a grade 3/6 holosystolic murmur at the apex without third or fourth heart sounds. His lungs were clear on auscultation, and there was no peripheral edema. The remainder of the complete examination revealed normal findings.
      Laboratory studies were notable for the following (reference ranges provided parenthetically): hemoglobin, 12.8 g/dL (13.5-17.5 g/dL); leukocyte count, 8.7 × 109/L (3.5-10.5 × 109/L); platelet count, 458 × 109/L (150-450 × 109/L); calcium, 12.8 mg/dL (8.9-10.1 mg/dL); creatinine, 1.2 mg/dL (0.8-1.3 mg/dL); troponin T, 0.07 ng/mL (<0.01 ng/mL); and N-terminal pro-B-type natriuretic peptide, 3575 pg/mL (<51 pg/mL). Urinalysis revealed proteinuria (3+), and chest radiography revealed a normal cardiac silhouette with clear lung fields. Electrocardiography (ECG) revealed normal sinus rhythm with criteria for low-voltage and Mobitz type 1 sinoatrial block.
      • 1.
        Which one of the following would be the most appropriate first diagnostic test to investigate the etiology of this patient’s cardiac symptoms?
        • a.
          Transthoracic echocardiography
        • b.
          Chest computed tomographic angiography
        • c.
          Treadmill exercise test
        • d.
          Cardiac catheterization
        • e.
          Endomyocardial biopsy
      This patient presented with a subacute onset of nonspecific cardiac symptoms, including dyspnea and syncope. Examination and laboratory findings are concerning for a systemic process with cardiac involvement. Transthoracic echocardiography is the best next step to determine the underlying etiology. Echocardiography provides a noninvasive assessment of overall cardiac function and is useful for evaluating valvular dysfunction and other structural abnormalities. Chest computed tomographic angiography would be useful for evaluation of pulmonary embolism, which should be a consideration in the setting of unexplained syncope. However, the chronicity of this patient’s symptoms and clinical stability make pulmonary embolism less likely. Treadmill exercise testing would be limited by our patient’s poor exercise capacity and recent exertional syncope. Cardiac catheterization and endomyocardial biopsy are invasive tests that are not urgently indicated in this situation.
      The patient underwent transthoracic Doppler echocardiography, which revealed increased concentric left ventricular wall thickness with a normal chamber size and ejection fraction. The averaged left ventricular longitudinal peak systolic strain was abnormal, with evidence of diastolic dysfunction. Left atrial enlargement, mitral valve thickening, and moderate regurgitation were noted. There was also increased right ventricular wall thickness with mildly elevated estimated right ventricular systolic pressure. The myocardium was noted to have increased echogenicity and a granular appearance.
      • 2.
        Given the constellation of findings, which one of the following is the most likely process causing the patient’s symptoms?
        • a.
          Hypertrophic nonobstructive cardiomyopathy
        • b.
          Infiltrative cardiomyopathy
        • c.
          Fenfluramine-phentermine–related cardiomyopathy
        • d.
          Ischemic cardiomyopathy
        • e.
          Chronic myocarditis
      Hypertrophic nonobstructive cardiomyopathy is unlikely because it most commonly presents with asymmetric left ventricular hypertrophy with septal thickening on echocardiography, and ECG often reveals high voltages. Physical examination, laboratory testing, and imaging findings suggest that our patient has an infiltrative cardiomyopathy secondary to an underlying systemic process. His ECG revealed conduction changes with low voltages, and his cardiac biomarkers are elevated. He has restrictive cardiac physiology on echocardiography, renal insufficiency, and proteinuria. These findings are concerning for an infiltrative process such as amyloidosis. Weight loss, nephrotic syndrome, and heart failure symptoms are especially concerning for AL (formerly called primary) amyloidosis. Although low voltage is the most common ECG abnormality in cardiac amyloidosis, conduction delay and arrhythmias are often present. Echocardiography classically shows a granular or sparkling appearance of the myocardium, but this is an insensitive finding with limited specificity. Ventricular wall thickening is usually symmetric with preserved cavity size, although this finding may be difficult to distinguish from hypertrophic nonobstructive cardiomyopathy. Cardiac biomarkers may be elevated in this disease. Use of a fenfluramine-phentermine combination may lead to weight loss, palpitations, and valvular disease but should not cause the echocardiographic findings seen in this case. Ischemic cardiomyopathy may result in decreased voltages on ECG but leads to dilated, eccentric ventricular hypertrophy with reduced ejection fraction. Myocarditis can lead to heart failure, arrhythmias, and elevated biomarkers. Echocardiographic findings in patients with myocarditis often include a dilated left ventricle with normal wall thickness and reduced ejection fraction.
      The patient underwent further laboratory investigation and assessment for a systemic infiltrative process.
      • 3.
        Which one of the following is the best laboratory evaluation at this time?
        • a.
          Serum protein electrophoresis
        • b.
          Urine protein electrophoresis
        • c.
          C-reactive protein
        • d.
          Transthyretin genetic testing
        • e.
          Serum free light chain assay
      Serum and urine protein electrophoresis are often performed when amyloidosis is suspected. However, these tests lack sensitivity, particularly when the amount of serum or urine paraprotein is small. If used, electrophoresis should be completed in conjunction with immunofixation to enhance sensitivity. C-reactive protein may be elevated in our patient, but this is a nonspecific laboratory test and is not indicated at this time. Transthyretin genetic testing is helpful in distinguishing senile systemic from hereditary amyloid disease but not in suspected cases of AL amyloidosis. Assays quantifying serum immunoglobulin free light chains are highly sensitive for AL amyloidosis and should be evaluated in this patient. This is a quantitative test, and monitoring of free light chain levels can be useful when determining response to therapy.
      Additional laboratory testing revealed elevated κ free light chains. Urine protein electrophoresis confirmed a monoclonal κ protein with an M-spike of 120 mg/dL in the gamma region.
      • 4.
        Which one of the following is the best next step to confirm the diagnosis of this patient’s cardiac process?
        • a.
          Fat pad aspirate
        • b.
          Skin biopsy
        • c.
          Renal biopsy
        • d.
          Endomyocardial biopsy
        • e.
          Bone marrow biopsy
      Amyloidosis resulting from an underlying plasma cell disorder is suspected, but tissue is required for definitive diagnosis. Fat pad aspiration with Congo red staining is the preferred initial biopsy specimen because of bleeding and complication risks associated with obtaining tissue from other sites. A skin biopsy is not indicated in this disease and is unlikely to identify amyloid involvement. Amyloid deposition can occur in multiple organs, and alternative biopsy locations include the kidney, liver, rectum, and myocardium. Sensitivity is often high from these sites, especially if there is clinical evidence of organ involvement. All patients with suspected AL amyloidosis should undergo bone marrow biopsy; however, this procedure is generally performed after confirmation of amyloid by fat pad aspiration. Involvement of bone marrow by more than 10% plasma cells with concomitant evidence of monoclonal protein and end-organ damage is diagnostic for multiple myeloma. If less invasive biopsy sites are nondiagnostic, right ventricular endomyocardial biopsy may be necessary. However, the combination of a positive result on a fat pad aspirate and classic ECG findings is sufficient for the diagnosis of cardiac amyloidosis.
      Our patient underwent fat pad aspiration, and the specimen was positive for amyloid on Congo red staining. He subsequently underwent bone marrow biopsy, which revealed hypercellular marrow and amyloidosis with 80% monoclonal κ plasma cells. Myeloma-associated AL amyloidosis was confirmed. His diffuse musculoskeletal pain was likely secondary to underlying multiple myeloma and associated hypercalcemia. A skeletal survey revealed scattered lucencies throughout the axial and appendicular skeleton, consistent with multiple myeloma.
      • 5.
        Which one of the following is the best therapeutic option for this patient?
        • a.
          Cardiac transplant
        • b.
          Implantable cardioverter-defibrillator placement
        • c.
          Systemic chemotherapy
        • d.
          Ventricular assist device placement
        • e.
          Plasmapheresis
      In addition to management of the cardiac manifestations in this patient, treatment of his underlying disease is paramount. This patient has multiple myeloma with evidence of diffuse AL amyloid deposition. Cardiac transplant is performed rarely because of concern for progressive disease and deposition in the donor organ.
      • Kapoor P.
      • Thenappan T.
      • Singh E.
      • Kumar S.
      • Greipp P.R.
      Cardiac amyloidosis: a practical approach to diagnosis and management.
      Implantable cardioverter-defibrillator therapy has not been found to improve mortality in cardiac amyloidosis, and the device may have reduced function due to myocardial infiltration.
      • Sharma N.
      • Howlett J.
      Current state of cardiac amyloidosis.
      The patient should be referred for systemic chemotherapy to decrease progressive organ dysfunction. Autologous stem cell transplant can be used in eligible patients to offer prolonged remission and definitive disease management. Ventricular assist devices are not routinely used in cardiac amyloidosis for multiple reasons, including restrictive cardiac physiology and associated procedural difficulty in affected individuals. Plasmapheresis can be used when symptoms of hyperviscosity are present but does not have a role in the management of this patient.
      Our patient began systemic chemotherapy with cyclophosphamide, bortezomib, and dexamethasone in anticipation of a future stem cell transplant. His free light chain level normalized with marked improvement in cardiac symptoms, biomarkers, and functional status. His proteinuria decreased as well. The patient subsequently received myeloablative chemotherapy in preparation for autologous stem cell transplant for definitive management of his myeloma-associated AL amyloidosis.

      Discussion

      Our patient presented with subacute symptoms of exertional dyspnea, weight loss, and palpitations. He also experienced a syncopal episode and diffuse musculoskeletal pain. Examination and laboratory findings were concerning for cardiac involvement by a systemic process. Echocardiography revealed a concentric increase in left ventricular wall thickness with enhanced echogenicity and preserved ejection fraction. Fat pad aspirate confirmed amyloid deposition, and subsequent bone marrow biopsy and skeletal survey results were consistent with multiple myeloma. This case highlights the diagnosis and management of cardiac manifestations in a patient with myeloma-associated AL amyloidosis.
      Amyloidosis refers to a collection of conditions in which abnormal protein folding results in insoluble fibril deposition in tissues. The disease can affect a multitude of organs throughout the body, including the heart, kidney, gastrointestinal tract, liver, and autonomic nervous system. The major types of amyloidosis, classified on the basis of their precursor protein, include light chain (AL), senile systemic (wild-type transthyretin), hereditary (mutant transthyretin), and secondary (AA) disease. The frequency of cardiac involvement varies among the types of amyloidosis and is common with senile systemic amyloidosis and light chain (AL) disease, as seen in this case.
      • Selvanayagam J.B.
      • Hawkins P.N.
      • Paul B.
      • Myerson S.G.
      • Neubauer S.
      Evaluation and management of the cardiac amyloidosis.
      The AL fibrils are derived from monoclonal immunoglobulin light chains and can be produced by a variety of plasma cell dyscrasias.
      • Falk R.H.
      • Comenzo R.L.
      • Skinner M.
      The systemic amyloidoses.
      These fibrils adopt a β-pleated sheet configuration rendering them insoluble when deposited extracellularly. Although uncommon, periorbital purpura due to capillary fragility may be seen in affected individuals and is indicative of amyloid deposition. This finding coupled with macroglossia is highly specific for AL amyloid disease.
      • Kapoor P.
      • Thenappan T.
      • Singh E.
      • Kumar S.
      • Greipp P.R.
      Cardiac amyloidosis: a practical approach to diagnosis and management.
      • Selvanayagam J.B.
      • Hawkins P.N.
      • Paul B.
      • Myerson S.G.
      • Neubauer S.
      Evaluation and management of the cardiac amyloidosis.
      The constellation of anemia, hypercalcemia, bony lesions, and renal dysfunction should prompt suspicion for multiple myeloma. Myeloma complicated by amyloidosis involves the deposition of light chain fibrils.
      • Palumbo A.
      • Anderson K.
      Multiple myeloma.
      When myocardium is involved, patients may present with nonspecific dyspnea, lower extremity edema, and syncope. Pulmonary edema is infrequent. Myocardial amyloid involvement leads to a restrictive cardiac physiology with possible concomitant conduction system disease. Blood pressure is often low and may be representative of decreased cardiac output with autonomic dysfunction.
      Approximately half of patients with AL amyloid will have low voltages on ECG (defined as limb leads <5 mm in height), and this is the most common finding in affected individuals.
      • Murtagh B.
      • Hammill S.C.
      • Gertz M.A.
      • Kyle R.A.
      • Tajik A.J.
      • Grogan M.
      Electrocardiographic findings in primary systemic amyloidosis and biopsy-proven cardiac involvement.
      A pseudoinfarct pattern with QS waves in any 2 consecutive leads is another frequent finding in cardiac amyloidosis. Criteria for left ventricular hypertrophy may be present in a subset of patients along with axis deviation. Affected individuals are prone to QTc prolongation as well as supraventricular, junctional, and ventricular arrhythmias. Conduction system disease can manifest as syncope or dysrhythmias, as seen in this case. Death in more than half of patients with cardiac amyloidosis is due to heart failure or refractory arrhythmia.
      • Selvanayagam J.B.
      • Hawkins P.N.
      • Paul B.
      • Myerson S.G.
      • Neubauer S.
      Evaluation and management of the cardiac amyloidosis.
      Echocardiography should be the first noninvasive test performed to evaluate for cardiac amyloidosis, although imaging alone cannot confirm the diagnosis. Echocardiographic findings include increased left ventricular wall thickness with diastolic dysfunction.
      • Klein A.L.
      • Hatle L.K.
      • Taliercio C.P.
      • et al.
      Serial Doppler echocardiographic follow-up of left ventricular diastolic function in cardiac amyloidosis.
      Ejection fraction is generally preserved. However, these findings are prevalent in other cardiac conditions and have poor specificity for amyloidosis. Increased myocardial echogenicity with a granular or sparkling appearance has been commonly described, although this description has limited sensitivity in cardiac amyloidosis and may be more indicative of late-stage disease.
      • Selvanayagam J.B.
      • Hawkins P.N.
      • Paul B.
      • Myerson S.G.
      • Neubauer S.
      Evaluation and management of the cardiac amyloidosis.
      • Klein A.L.
      • Hatle L.K.
      • Taliercio C.P.
      • et al.
      Serial Doppler echocardiographic follow-up of left ventricular diastolic function in cardiac amyloidosis.
      Patients with more advanced disease can present with right ventricular thickening and diastolic dysfunction, atrial enlargement, and valvular changes. Pericardial effusion is a common finding. Cardiovascular magnetic resonance imaging is an emerging diagnostic technique with increasing utility in evaluating and recognizing cardiac amyloidosis. Left ventricular late gadolinium enhancement and suboptimal nulling of the myocardium are highly suggestive of the disease and seem to be more sensitive for amyloid deposition than echocardiography.
      • Maceira A.M.
      • Joshi J.
      • Prasad S.K.
      • et al.
      Cardiovascular magnetic resonance in cardiac amyloidosis.
      However, gadolinium contrast is contraindicated in moderate to severe renal dysfunction, which is a common manifestation in patients with systemic amyloid deposition.
      Serum laboratory screening for suspected AL amyloidosis should include free light chain assays or immunofixation, as these tests have high sensitivity for the disease. Tissue is required for the definitive diagnosis of amyloidosis. The criterion standard for diagnosing cardiac amyloidosis is endomyocardial biopsy, although this is often unnecessary if echocardiographic findings are suggestive of disease and histologic diagnosis can be made from other tissue.
      • Falk R.H.
      Diagnosis and management of the cardiac amyloidosis.
      • Guan J.
      • Mishra S.
      • Falk R.H.
      • Liao R.
      Current perspectives on cardiac amyloidosis.
      Tissue biopsy revealing apple green birefringence when stained with Congo red and visualized under polarized light is diagnostic. Amyloid-positive biopsy specimens should undergo further analysis with mass spectrometry to determine the subtype.
      • Kapoor P.
      • Thenappan T.
      • Singh E.
      • Kumar S.
      • Greipp P.R.
      Cardiac amyloidosis: a practical approach to diagnosis and management.
      Investigation for an underlying plasma cell dyscrasia with bone marrow biopsy is indicated when AL amyloid deposition is established.
      • Falk R.H.
      Diagnosis and management of the cardiac amyloidosis.
      The most common plasma cell dyscrasia is multiple myeloma, although only a minority of patients with myeloma have development of amyloidosis.
      • Klein A.L.
      • Hatle L.K.
      • Taliercio C.P.
      • et al.
      Serial Doppler echocardiographic follow-up of left ventricular diastolic function in cardiac amyloidosis.
      The presence of at least 10% clonal plasma cells in the bone marrow with associated organ dysfunction and monoclonal protein in the serum or urine is diagnostic for myeloma.
      • Palumbo A.
      • Anderson K.
      Multiple myeloma.
      Skeletal survey is required to identify myeloma-associated bone lesions.
      Troponin T elevation, as seen in this case, suggests ongoing myocyte damage and has been shown to be a negative prognostic factor.
      • Falk R.H.
      Diagnosis and management of the cardiac amyloidosis.
      • Dispenzieri A.
      • Gertz M.A.
      • Kyle R.A.
      • et al.
      Serum cardiac troponins and N-terminal pro-brain natriuretic peptide: a staging system for primary systemic amyloidosis.
      Both troponins and N-terminal pro-B-type natriuretic peptide serve as independent predictors of survival in patients with AL amyloidosis.
      • Dispenzieri A.
      • Gertz M.A.
      • Kyle R.A.
      • et al.
      Serum cardiac troponins and N-terminal pro-brain natriuretic peptide: a staging system for primary systemic amyloidosis.
      Once congestive heart failure occurs in AL amyloidosis, median survival if left untreated is less than 6 months.
      • Guan J.
      • Mishra S.
      • Falk R.H.
      • Liao R.
      Current perspectives on cardiac amyloidosis.
      Thus, prompt recognition of symptoms, diagnosis, and initiation of therapy is imperative.
      Management of cardiac amyloidosis involves treatment of cardiac symptoms as well as the underlying systemic process. The mainstay of therapy for AL amyloid cardiomyopathy involves the use of diuretics.
      • Selvanayagam J.B.
      • Hawkins P.N.
      • Paul B.
      • Myerson S.G.
      • Neubauer S.
      Evaluation and management of the cardiac amyloidosis.
      • Falk R.H.
      Diagnosis and management of the cardiac amyloidosis.
      If concomitant nephrotic syndrome is present, high doses may be required to achieve a euvolemic fluid status. Although there is no data supporting their effectiveness in amyloidosis, β-blockers may be used in selected patients with associated tachydysrhythmias, but close monitoring and dose titration are imperative. Bradycardia, conduction delay, and hypotension limit the role of β-blockade in cardiac amyloidosis. The use of angiotensin-converting enzyme inhibitors and angiotensin inhibitors in cardiac amyloidosis remains controversial, and these agents should be administered with caution because of their potential for profound hypotension. Calcium channel blockers are contraindicated in patients with cardiac amyloidosis because of their negative inotropic effects.
      • Selvanayagam J.B.
      • Hawkins P.N.
      • Paul B.
      • Myerson S.G.
      • Neubauer S.
      Evaluation and management of the cardiac amyloidosis.
      • Falk R.H.
      Diagnosis and management of the cardiac amyloidosis.
      Digoxin also binds avidly to myocardial amyloid, and although the degree of pharmacological effect is uncertain, its use could lead to increased toxicity.
      • Kapoor P.
      • Thenappan T.
      • Singh E.
      • Kumar S.
      • Greipp P.R.
      Cardiac amyloidosis: a practical approach to diagnosis and management.
      • Falk R.H.
      Diagnosis and management of the cardiac amyloidosis.
      The definitive treatment of AL-type cardiac amyloidosis is aimed at eradication of the underlying plasma cell disorder with prevention of successive free light chain production and amyloid deposition. Disrupting pathologic protein production can result in disease regression, preservation of organ function, and prolonged survival.
      • Rosenzweig M.
      • Landau H.
      Light chain (AL) amyloidosis: update on diagnosis and management.
      Multiple chemotherapeutic regimens are available, and regimens vary on the basis of the patient’s ability to tolerate therapy, organ involvement, and presence of underlying myeloma. The most common regimens are melphalan based, although the use of newer agents such as the proteasome inhibitor bortezomib is becoming first-line treatment for patients with advanced cardiac involvement.
      • Sharma N.
      • Howlett J.
      Current state of cardiac amyloidosis.
      • Rosenzweig M.
      • Landau H.
      Light chain (AL) amyloidosis: update on diagnosis and management.
      If patients are eligible, myeloablative chemotherapy with subsequent stem cell transplant can be pursued. Response is variable, but a sustained reduction of monoclonal light chain values by greater than 50% has been associated with increased survival.
      • Selvanayagam J.B.
      • Hawkins P.N.
      • Paul B.
      • Myerson S.G.
      • Neubauer S.
      Evaluation and management of the cardiac amyloidosis.
      Cardiac amyloidosis increases morbidity and mortality from autologous stem cell transplant, and the presence of New York Heart Association class III or IV heart failure is largely considered a contraindication.
      • Selvanayagam J.B.
      • Hawkins P.N.
      • Paul B.
      • Myerson S.G.
      • Neubauer S.
      Evaluation and management of the cardiac amyloidosis.
      • Falk R.H.
      Diagnosis and management of the cardiac amyloidosis.
      Therefore, early diagnosis is crucial before the disease progresses to the point that patients are unable to tolerate therapy.
      Cardiac amyloidosis is characterized by amyloid deposition in the myocardium, resulting in restrictive physiology and subsequent heart failure. Characteristic ECG and echocardiographic findings can be suggestive of infiltrative disease. Diagnosis requires tissue biopsy, although laboratory studies can provide useful prognostic indicators. Cardiac amyloidosis results in poor survival if left untreated. Early recognition and diagnosis is imperative so that timely therapy can be initiated in an attempt to improve patient outcomes.

      References

        • Kapoor P.
        • Thenappan T.
        • Singh E.
        • Kumar S.
        • Greipp P.R.
        Cardiac amyloidosis: a practical approach to diagnosis and management.
        Am J Med. 2011; 124: 1006-1115
        • Sharma N.
        • Howlett J.
        Current state of cardiac amyloidosis.
        Curr Opin Cardiol. 2013; 28: 242-248
        • Selvanayagam J.B.
        • Hawkins P.N.
        • Paul B.
        • Myerson S.G.
        • Neubauer S.
        Evaluation and management of the cardiac amyloidosis.
        J Am Coll Cardiol. 2007; 50 ([published correction appears in J Am Coll Cardiol. 2011;57(13):1501]): 2101-2110
        • Falk R.H.
        • Comenzo R.L.
        • Skinner M.
        The systemic amyloidoses.
        N Engl J Med. 1997; 337: 898-909
        • Palumbo A.
        • Anderson K.
        Multiple myeloma.
        N Engl J Med. 2011; 364: 1046-1060
        • Murtagh B.
        • Hammill S.C.
        • Gertz M.A.
        • Kyle R.A.
        • Tajik A.J.
        • Grogan M.
        Electrocardiographic findings in primary systemic amyloidosis and biopsy-proven cardiac involvement.
        Am J Cardiol. 2005; 95: 535-537
        • Klein A.L.
        • Hatle L.K.
        • Taliercio C.P.
        • et al.
        Serial Doppler echocardiographic follow-up of left ventricular diastolic function in cardiac amyloidosis.
        J Am Coll Cardiol. 1990; 16: 1135-1141
        • Maceira A.M.
        • Joshi J.
        • Prasad S.K.
        • et al.
        Cardiovascular magnetic resonance in cardiac amyloidosis.
        Circulation. 2005; 111: 186-193
        • Falk R.H.
        Diagnosis and management of the cardiac amyloidosis.
        Circulation. 2005; 112: 2047-2060
        • Guan J.
        • Mishra S.
        • Falk R.H.
        • Liao R.
        Current perspectives on cardiac amyloidosis.
        Am J Physiol Heart Circ Physiol. 2012; 302: H544-H552
        • Dispenzieri A.
        • Gertz M.A.
        • Kyle R.A.
        • et al.
        Serum cardiac troponins and N-terminal pro-brain natriuretic peptide: a staging system for primary systemic amyloidosis.
        J Clin Oncol. 2004; 22: 3751-3757
        • Rosenzweig M.
        • Landau H.
        Light chain (AL) amyloidosis: update on diagnosis and management.
        J Hematol Oncol. 2011; 4: 1-8