Ventricular Fibrillation after Bortezomib Therapy in a Patient with Systemic Amyloidosis
A 64-year-old female suffering from general fatigue, appetite loss, and weight loss was referred to our institute for the investigation of M-protein and hypercalcemia. Upon hospital admission, her Eastern Cooperative Oncology Group performance status was 2 and her Karnofsky performance status (KPS) was approximately 50%. She was also found to suffer from class II heart failure according to the functional classification system of New York Heart Association (NYHA). Physical examination revealed a palpable liver edge 15 cm below the costal margin and bilateral pretibial pitting edema.\nResults of her blood test revealed the following: aspartate aminotransferase, 81 (normal, 13-33) U/L; alkaline phosphatase, 534 (115-359) U/L; γ-glutamyl transpeptidase, 311 (10-47) U/L; lactate dehydrogenase, 343 (119-229) U/L; calcium, 11.7 (8.7-10.3) mg/dL; creatinine, 1.18 (0.4-0.7) mg/dL; brain natriuretic peptide (BNP), 1630.5 (0-8.4) pg/mL; N-terminal prohormone of BNP (NT-proBNP), 8290 (0-125) pg/mL; and troponin T, 0.242 (0-0.014) ng/mL. Her serum beta-2 microglobulin level was 5.5 (0-2.5) mg/L and free light chain difference (FLC-diff) was 33.46 mg/dL.\nImmunoelectrophoresis demonstrated a monoclonal immunoglobulin light-chain with λ isotype in the urine. A bone marrow aspirate revealed 10% plasma cells with CD38+, CD138+, and cytoplasmic λ+ phenotypes. An iliac biopsy confirmed the infiltration of plasma cells. Diffuse osteoporosis was revealed by radiography, and magnetic resonance imaging showed the absence of focal lesions. Histopathological examination revealed amyloid infiltration in biopsy samples of the gastric mucosa.\nMarked cardiomegaly was noted on chest radiography. Electrocardiography (ECG) revealed left-axis deviation, low-voltage QRS complexes, and first degree atrioventricular block (). A 24-h Holter ECG demonstrated 129 beats of ventricular premature contractions (VPCs) and 1268 beats of atrial premature contractions (APCs), including 5 VPC short runs (maximum, 5 runs) and APC short runs (maximum, 8 runs; ). Transthoracic echocardiography revealed a left ventricular ejection fraction of 64%, diffuse thickening of the left and right ventricular walls with granular sparkling, and pericardial effusion.\nShe was diagnosed with systemic AL amyloidosis associated with Bence Jones protein type multiple myeloma (MM). After written informed consent was obtained from the patient, administration of dexamethasone and bortezomib (oral dexamethasone, 20 mg/day, days 1-4; bortezomib, 1.3 mg/m2/day, subcutaneous injection on day 4) was initiated under 24-h ECG monitoring (). The incidence of tachycardia was decreased through dexamethasone treatment. Serum calcium levels were corrected by intravenous infusions of normal (0.9%) saline with elcatonin, leading to increased body weight. After adjustment of infusions and diuretic treatment, her body weight returned to that at baseline. The day before the onset of VF, her serum mineral levels were within normal limits as follows: calcium, 9.2 mg/dL; magnesium, 1.8 (1.8-2.7) mg/dL; and potassium, 3.9 (3.6-4.9) mmol/L. The patient no longer complained of insomnia, constipation, or the stress of hospital admission. However, approximately 84 h after bortezomib administration, in the middle of the night, the patient conversed with nursing staff and walked to the rest room for urination. A few minutes later, her cardiac monitor alarm sounded and showed VF pattern. She was found lying down at her bedside. Cardiopulmonary resuscitation (CPR) using direct current shocks with epinephrine and amiodarone was initiated. Her serum mineral levels were as follows: sodium, 138.1 (138-146) mmol/L; potassium, 3.56 mmol/L; ionized calcium, 1.11 (1.1-1.4) mmol/L; and bicarbonate, 29.9 (22-30) mmol/L. Continuous CPR for approximately 30 min failed to recover the cardiac features required to sustain the general circulation, but just after the injection of vasopressin, her arterial pulsations recovered. However, she died of heart failure 8 h after the onset of VF.\nAutopsy revealed congested, hemorrhagic lungs and right and left ventricular hypertrophy (heart weight, ≥400 g). Gross examination revealed round-to-web-like yellow waxy deposits in the myocardium. Histopathological examination revealed cardiac amyloid deposition, even in the atrioventricular node, and no ischemic lesion was complicated (). The amyloidosis had also spread to the tongue, lung, liver, colon, kidney, bone marrow, adrenal gland, thyroid gland, and ovaries.