Cardiac Tamponade Associated With Azacitadine Use in a Patient With Myelodysplastic Syndrome

Abstract

INTRODUCTION: Myelodysplastic syndromes (MDS) are a group of myeloid clonal disorders that have a heterogeneous spectrum of disease. The clinical presentation arises from cytopenias with potential to evolve into acute myeloid leukemia. Definitive cure may be attained via allogenic hematopoietic stem cell transplantation, however hypomethylating agents, such as Azacitadine, are commonly used as treatment. Common side effects include inhibition of hematopoietic cells, nausea, liver and kidney injury. Pan-serositis is a rare side effect and infrequently reported. Moreover, acute pericardial tamponade is a side effect not previously described in the literature. CASE PRESENTATION: A 58-year-old man with untreated high risk MDS presented with one week of worsening dyspnea. He was hemodynamically stable with an unremarkable physical exam. Laboratory testing revealed a hemoglobin of 6.2g/dl and symptoms were attributed to acute on chronic anemia. Computed tomography (CT) angiography of the chest showed normal perfusion, normal lung parenchyma and heart size with no pericardial effusion. Symptoms and anemia resolved with multiple transfusions of packed red blood cells. Bone marrow biopsy showed 10-15% myeloblasts with dysplastic changes, and he was started on cytotoxic therapy with Azacitidine as a bridge to potential transplant. On day five of treatment, he developed a dry cough and dyspnea that progressed over the next days. One day after finishing the 7-day course of Azacitatine, CT of the chest revealed a moderate to severe pericardial effusion with no right heart strain and large bilateral pleural effusions. Vital signs were notable for borderline hypotension with mild tachycardia. He had muffled heart sounds and diminished bilateral lower lobe breath sounds. Echocardiogram showed signs of impending cardiac tamponade. Emergency pericardial window with subsequent bilateral chest tube insertion was performed. Fluid studies showed no evidence of underlying malignant infiltration or infectious etiology. Further treatment with Azacitabine was held and symptoms resolved. DISCUSSION: Azacitidine causes demethylation of genes involved in cell-cycle regulation, apoptosis and cell adhesion, which are associated with disease progression in MDS. Pericardial effusions have rarely been reported as a side effect of this medication, and to our knowledge, there are no reports in the literature describing the development of acute pericardial tamponade. The Naranjo drug reaction probability scale was 6 indicating probable adverse reaction. Possible mechanisms suggest an underlying cascade of immune mediated delayed hypersensitivity caused by the chemotherapy. CONCLUSIONS: Further analysis is needed to determine the cardiotoxic side-effect profile of hypomethylating agents in order to improve awareness and therefore prompt recognition of a potentially life-threatening event such as acute pericardial tamponade.