Case Description

A 66-year-old male with a history of hypertension and hypothyroidism was referred to stress echocardiography as part of the evaluation of new-onset bilateral leg enema. Initial resting echocardiography revealed a preserved left ventricle ejection fraction (LVEF) of 55%, with moderately reduced right ventricle (RV) function and elevated systolic pulmonary artery pressure (SPAP) of 53 mmHg. During the stress test, the patient developed rapid atrial fibrillation (AF) and underwent electrical cardioversion, with resultant failure to preserve sinus rhythm. Five months later the patient was readmitted due to chest pain and dyspnoea in the presence of increased troponin levels. Electrocardiogram (ECG) showed normal sinus rhythm (75 beats per minute) with right bundle branch block (RBBB) and 1st-degree atrioventricular block. The ECG’s voltage was normal, with no signs of ischemia (Figure 1). Echocardiography demonstrated mild segmental defect with a LVEF of 50%, mild LV hypertrophy with an interventricular septum (IVS) of 13mm, grade 2 diastolic dysfunction with increased E/A ratio and decreased deceleration time (Figure 2), mildly dilated right ventricle and moderate pulmonary hypertension of 51mmHg. The patient was then referred for coronary angiography, which revealed angiographically normal coronary arteries, and the diagnosis remained unclear. Based on the patient’s symptoms of heart failure, angina, elevated troponin levels, paroxysmal AF, increased IVS, and diastolic dysfunction; all in the absence of coronary disease, a suspicion for infiltrative cardiomyopathy was raised. A pyrophosphate nuclear scintigraphy was performed, excluding transthyretin–related amyloidosis. Endomyocardial biopsy showed perivascular depositions of eosinophilic amorphous hyaline material, which stained positively to Congo red staining, representing amyloid deposits. Further blood work revealed a monoclonal lambda spike with increased free light chain levels in the blood (1400 MG/L) and a reduced Kappa/Lambda ratio of 0.01. Bone marrow biopsy showed infiltration with 11% monoclonal plasma cells. Congo red stain was negative. According to the symptoms, cardiac biomarkers and endomyocardial biopsy, the patient was diagnosed with cardiac amyloid light-chain (AL) amyloidosis. Troponin and Pro-Brain natriuretic peptide (Pro-BNP) (10355pg/ml) were both elevated; compatible with rMAYO score 4 [1]. Due to suspicious lung nodules found during the nuclear scintigraphy scan, the patient underwent a Positron Emission Tomography-Computed Tomography (PET- CT) that demonstrated an abdominal mass with lesions suspicions for metastases to the liver and lungs. Biopsy taken from the abdominal mass confirmed the diagnosis of leiomyosarcoma (LMS). The patient was thus simultaneously diagnosed with primary AL amyloidosis and metastatic LMS. While the preferred therapy for LMS is an anthracycline-based regimen, it is risky to administer in this setting due to its cardio toxic potential [2], and data is limited regarding the use of anthracyclines in grade 4 cardiac AL amyloidosis patients. Following a multidisciplinary Concilium of Haematologist, Oncologist and Cardiologist, the patient was initiated with a protocol therapy of bortezomib for his cardiac AL amyloidosis and gemcitabine and paclitaxel for his LMS. Due to symptomatic heart failure (HF), consistent with New York Heart Association III, spironolactone and furosemide were initiated. At that time point, the patient was treated with 2 cycles of bortezomib (1.3 mg/m^2, once weekly) followed by 2 cycles of daratumumab (16 mg/kg), administered in combination with doxycycline 100 mg twice a day, and 2 courses of gemcitabine (1000 mg/m2 given on days 1 and 8 every 21 days) and paclitaxel (175 mg/m2 on day 8 every 21 days). At a 30-day assessment, following the initiation of protocol therapy, a gradual decrease in Lambda levels was observed (Table 1). Follow-up CT showed a right abdominal mass (9.6*9.2cm) with multiple metastases to the liver and lungs (Figure 3). Two days following daratumumab therapy and 8 days following gemcitabine therapy, with an overall 37 days from the initiation of therapy, the patient was referred to the emergency room due to diarrhea and a mechanical fall. While waiting in the emergency room, the patient lost consciousness and cardiopulmonary resuscitation was initiated. Initial blood tests later revealed pancytopenia, acute on chronic renal failure, elevated troponin and BNP, and elevated C-reactive protein (Table 1). Despite appropriate resuscitative efforts, the patient passed away.

Figure 1: Electrocardiogram performed on patient’s index presentation.