Case Discussion <Case Presentation>      A 56-year-old man was admitted to the hospital because of intolerable orthopnea and paroxysmal nocturnal dyspnea.      This patient had a history of diabetes mellitus for more than one year under regular use of oral hypoglycemic agents. Progressive dyspnea on exertion and edema of lower legs developed in 1 month before admission. He denied chest pain, symptoms of upper respiratory infection, or fever. He denied taking Chinese herbs. On physical examination, the blood pressure was 90/60mmHg, the temperature was 36.6oC, the pulse was 90 and the respirations were 26. The neck jugular vein was engorged. Bilateral pulmonary crackles were heard. The heart sounds were normal. His abdomen was distended with shifting dullness. There was severe peripheral edema (+++). Electrocardiography (Fig. 1) and chest X-ray (Fig. 2 ) were performed. An echocardiography showed left ventricular ejection fraction of 45% and concentric left ventricular hypertrophy. Oral digoxin and intravenous nitroglycerine were administered.      However, the dyspnea and chest tightness deteriorated weeks later. A follow-up echocardiography revealed generalized cardiac hypokinesia and left ventricular ejection fraction of 30 %. He was sent to the intensive care unit because of shock status. Low dose dopamine and angiotensin converting enzyme inhibitor (ACEI) were given to control his congestive heart failure. Cardiac catheterization with biopsy was performed. The catheterization data showed high left and right ventricular end-diastolic pressure. Restrictive cardiomyopathy was suspected, and endomyocardial biopsy was performed. The pathology report showed amyloidosis. Bone marrow biopsy revealed an increased plasma cell ratio. Under the use of diuretics and dobutamine, his symptoms improved gradually. The nerve conduction velocity showed bilateral carpel tunnel syndrome and sensorimotor neuropathy. The significant laboratory values were summarized as following. <Laboratory values> Hematologic laboratory values Date RBC Hb Hct MCV Plt WBC  Seg  Lym On admission 3.26 10.3 31 95.1 143 5720 61.6 26.7 On 10th hospital day 2.86 9.0  27.5 96.2 170 5350 64.1 22.8 On 20th hospital day 2.7 8.4 26.6 98.3 135 5430 74.7 15.5  Blood chemical values. Date A/G Bil-T/D GOT GPT ALP GGT  LDH CRP On admission 3.99/4.4  0.81/0.3 66 5 88 135   0.95 On 10th hospital day 3.74/3.6 0.26 28 28         On 20th hospital day               2.18                 Date BUN Cre Na K Ca Mg On admission 28.6 1.02 135.9 6.76(h3) 2.23   On 10th hospital day 34.5 1.59 136.8 4.4 2.19   On 20th hospital day 27.5 1.26 134.6 3.93                   On admission CK/CK-MB/Troponin-I: 81/36.8/1.2 Nerve conduction velocity on 24th hospital day: sensorimotor polyneuropathy, superimposed with entrapment neuropathy involving bilateral median nerves at the wrist, carpel tunnel syndrome. Echocardiography: On admission: LVEF 63%, LA 41 (19-40), AO 23 (20-37), AV 19 (16-26), IVS 16 (7-10), LVPW 18 (8-13), LVEDD 38 (35-53), LVESD 25 (20-35), mild MR, Mild TR, AV flow 99cm/s (PG 3), MV flow E 111 A 29, Minimal pericardial effusion On 10th hospital day: LVEF 61%, mitral flow 112 in inspiration, 96.6 in expiration minimal pericardial effusion, TR 245 (PG 24) Swan-Ganz data on 10th hospital day: C.I. 2.05 SVRI 2220 PVRI 506 PAWP 26 CVP 325 Cath data on 5th hospital day: patent coronary arteries, LVEF 56%, LV 108/31, RV 57/26, thick LV Autoimmune profile on 9th hospital day: RA factor <20, ANA 1:40, C3 87.6, C4 22.8 Serum IFE on 10th hospital day: a dense IgA/λmonoclonal gammopathy Urine electrophoresis: a monoclonal gammopathy Urine IFE: a dense lambda Bence-Jones protein IgG 594 (1140-1700), IgA 2200 (180-340), IgM 25.2 (90-230), β2-micoglobulin 8.367 (0.7-2.0) Anti-HCV (-), HBsAg (-)  病案分析       本病例為一典型之鬱血性心衰竭的患者，其臨床表現包括：dyspnea，orthopnea，paroxysmal nocturnal dyspnea，neck vein distension以及extremity edema等等。慢性之鬱血性心衰竭常伴隨四個房室的擴大，如本病例在胸部X光與心臟超音波所見。下肢水腫雖可見於其他疾病，但同時合併頸靜脈怒張、腹脹與腹水時，再加上腎功能與肝功能正常就幾乎可以排除由心臟以外的疾病所引起的問題。       限制性心肌病變之主要特色為異常的心臟舒張功能。原因為心室壁過度僵硬，而導致心室充填受到阻礙。其可能發生之原因包括：amyloidosis，hemochromatosis，glycogen deposition，endomyocardial fibrosis，sarcoidosis等等。各種癌症浸潤引發之心肌病變也是可能因素之一。本病例就是極為罕見的由multiple myeloma引起的限制性心肌病變。在臨床診斷上，必須仰賴right ventricular transvenous endomyocardial biopsy才能確立最後的診斷，治療之預後通常也不理想。           繼續教育考題 1. (A) Which of the following is not included in the major Framingham criteria for diagnosis of congestive heart failure? A Extremity edema. B Neck vein distension. C Rales. D Acute pulmonary edema. E S3 gallop. 2. (C) Which of the following disorders can lead to both cardiogenic and noncardiogenic pulmonary edema? A Gram-negative septicemia. B Heroine overdose. C Sarcoidosis. D Central nervous system disorders. E Exposure to high altitude. 3. (A) Which of the following statements about restrictive cardiomyopathy is not true? A  The restrictive cardiomyopathy is characterized by impairment to ventricular contraction. B The cardiac silhouette is usually mildly enlarged. C ECG typically shows low-voltage QRS complexes. D Echocardiography usually reveals normal systolic and increased left ventricular wall thickness. E All of the above statements are true. 4. (B) Which of the following disease will result in a speckled appearance of thickened left ventricular wall in echocardiography? A Alcoholic cardiomyopathy. B Amyloidosis. C Hemochromatosis. D Viral myocarditis. E Tuberculosis. 5. (E) Which of the following criteria is not considered as with high estimated tumor burden of multiple myeloma? A Hemoglobin < 8.5 g/L. B Serum calcium >3 mmol/L. C Advanced lytic bone lesions D High M-component production. E Platelet < 100 K/mm3. 6. (D) What item below is false to differentiate restrictive cardiomyopathy from constrictive pericarditis? A Pericardial knock may be present in constrictive pericarditis but usually absent in restrictive cardiomyopathy B Pulsus paradoxus may be present in both restrictive cardiomyopathy and constrictive pericarditis C Equal RV and LV diastolic pressure cannot exclude restrictive cardiomyopathy D In restrictive cardiomyopathy, early diastolic filling tends to excessively rapid in contrast to constrictive pericarditis E S3 gallop can exist in restrictive cardiomyopathy 7. (C) Which item below is not an ever-documented etiology of restrictive cardiomyopathy? A Carcinoid B Anthracycline toxicity C Penicillamine toxicity D Metastatic malignancy E Radiation 8. (C) What item below is true about primary amyloidosis? A Carpal tunnel syndrome is a common manifestation B Rectal, skin or fat pad biopsy often shows amyloid deposition C Isolated cardiac amyloidosis can often be cured with heart transplantation D Bone marrow transplantation is the only way to cure E Primary amyloidosis is the most common etiology of infiltrative restrictive cardiomyopathy 9. (A) What item below is false about restrictive cardiomyopathy due to amyloidosis? A Digoxin is beneficial for controlling arrhythmia B Rapidly progressive bi-ventricular failure is common C Sudden death as a result of arrhythmic in origin is relatively common D Orthostatic hypotension is a common manifestation E Although angina pectoris is common, the coronary arteries usually are patent 10. (A) Which chromosome abnormality is not common in myeloma? A  t(8;14) B –13q14 C –17p13 D 11q abnormality E  t(11;14)

答案解說 (A) Extremity edema is one of the minor criteria for the diagnosis of congestive heart failure. (C) Sarcoidosis can cause both cardiogenic and noncardiogenic pulmonary edema. (A) Restrictive cardiomyopathy is characterized by impairment to ventricular relaxation. (B) Speckled appearance of thickened left ventricular wall in echocardiography is a specific finding of cardiac amyloidosis. (E) Thrombocytopenia is not included in the criteria for the diagnosis of high tumor burden in multiple myeloma. (D) In constrictive pericarditis, early diastolic filling tends to be excessively rapid in contrast to restrictive cardiomyopathy (C) All other items have been documented to cause restrictive cardiomyopathy. (C) Heart transplantation only cannot cure cardiac amyloidosis, which will recur definitely. (A) Digoxin may selectively bind to amyloid fibrils in the myocardium, and lead to severe arrhythmia. Therefore, digoxin should be used extremely cautiously in cardiac amyloidosis. (A ) t(8;14) is common in Burkitt’s lymphoma rather myeloma.