The Yield of Echocardiography in the Diagnosis of Infective Endocarditis in Patients Undergoing Chemotherapy for Acute Myeloid Leukemia

Abstract

INTRODUCTION:The pathogenesis of infective endocarditis (IE) , a typical biofilm-associated infectious disease frequently caused by commensal or pathogenic bacteria, is mainly attributed to the formation of septic vegetations, which are fibrin-platelet complexes embedded with bacteria on heart valves detected by echocardiography. Patients with acute myeloid leukemia (AML) are prone to neutropenia, immunosuppression and central venous catheters leading to high rates of bacteremia. It has been postulated that despite high rates of bacteremia, patients with AML undergoing intensive chemotherapy are only rarely able to form vegetations due the frequent thrombocytopenia associated with such treatment (McCormick 2002). Here, we sought to determine the rate of echocardiographic detection of IE in patients with AML and chemotherapy induced thrombocytopenia .METHODS:To assess the yield of echocardiography, we conducted a retrospective, single center, analysis of patients with AML who underwent treatment using anthracycline or fludarabine induction and intermediate/high dose cytarabine based consolidation. At all time points, patients with febrile neutropenia were empirically treated with piperacillin/tazobactam ± aminoglycosides and underwent appropriate investigations including blood cultures. Cultures were drawn every 24 to 48 hours with fevers and daily, if positive, till culture clearance. Patients with positive blood cultures for organisms associated with IE underwent an echocardiogram as standard of care.RESULTS:From January 2010 to January 2018, 296 patients underwent curative intent chemotherapy for treatment of acute myeloid leukemia (AML) at the University of Alberta Hospital, Edmonton, Canada. The median age of all patients was 56.7 years (IQR: 44-64) and 40.2% were females. During the induction or consolidation chemotherapy , 53 echocardiogram were done to investigate 53 episodes of bacteremia in 50 patients (16.9%) who had organisms associated with IE (Table 1). Two echocardiograms were done to investigate possible culture negative IE based upon clinical suspicion. Transesophageal echocardiogram were utilized in 19 patients (36%) while transthoracic echocardiogram were done in 34 patients (64%). The median platelets count on the day of the echocardiogram was 23 x109/L (IQR: 14-38). Viridans Group Streptococci and Staphylococcus aureus were the most frequent isolates cultured in the blood in 36% and 16% of cases, respectively. The median duration of bacteremia was 1 day (IQR 1-2). Three (5.6%) patients had echocardiographic findings suggestive of IE based on a positive transesophageal study (n=2) or transthoracic study (n=1). Among these, two were secondary to Enterococcus bacteria and involved the mitral valve and the third was secondary to a non-HACEK gram-negative bacteria leading to tricuspid valve involvement .CONCLUSION:This study is the first to suggest that despite the high prevalence of Viridans Group Streptococci and Staphylococcusaureus in patients with AML undergoing chemotherapy, echocardiographic findings of IE in these patients are rare, with the notable exception of Enterococcal and Non-HACEK gram negative organisms. In contrast, in the general population, Viridans Group Streptococci and Staphylococcus aureus and bacteremia are associated with IE in 20% and 63% %, respectively (Westling 2009, Rasmussen 2011). The low incidence in our cohort may be attributed to impaired fibrin-platelet deposition in these patients with inability to mount a vegetation response, or the early initiation of broad spectrum antibiotics. Given these findings, the value of routine echocardiography should be questioned in patients with AML without other clinical features of IE. DisclosuresSandhu:Bioverativ: Honoraria; Celgene: Honoraria; Novartis: Honoraria; Janssen: Honoraria; Amgen: Honoraria. Brandwein:Pfizer: Consultancy; Celgene: Consultancy; Boehringer Ingelheim: Consultancy, Research Funding; Novartis: Consultancy; Lundbeck: Consultancy.