Dilated cardiomyopathy following anthracycline-based chemotherapy in a tropical setting: R-CHOP and Chagas disease (a case report)

¹French Guiana University Hospital/Saint-Laurent-du-Maroni Site, Hemato-Oncology Day Hospital Unit, Saint-Laurent-du-Maroni, French Guiana, ²French Guiana University Hospital/Saint-Laurent-du-Maroni Site, Nephrology and Dialysis Unit, Saint-Laurent-du-Maroni, French Guiana, ³French Guiana University Hospital/Saint-Laurent-du-Maroni Site, Cardiology Unit, Saint-Laurent-du-Maroni, French Guiana, ⁴French Guiana University Hospital/Saint-Laurent-du-Maroni Site, Internal Medicine Unit, Saint-Laurent-du-Maroni, French Guiana

^&Corresponding author
Arriel Makembi Bunkete, French Guiana University Hospital/Saint-Laurent-du-Maroni Site, Nephrology and Dialysis Unit, Saint-Laurent-du-Maroni, French Guiana

Introduction    

Dilated cardiomyopathy (DCM) is a severe myocardial disorder characterized by ventricular dilation and systolic dysfunction, ultimately leading to heart failure. It represents a major cause of morbidity and mortality worldwide, with multiple etiologies, including genetic mutations, viral infections, autoimmune conditions, and exposure to cardiotoxic agents such as anthracyclines. Among cancer patients, anthracycline-induced cardiotoxicity is a well-documented phenomenon, with its incidence being dose-dependent and potentially leading to irreversible cardiac damage [1].

In tropical regions, where infectious diseases remain highly prevalent, an additional layer of complexity arises when diagnosing and managing DCM. Chagas disease, caused by the protozoan parasite Trypanosoma cruzi, remains a significant public health concern in Latin America and has been increasingly detected in non-endemic areas due to migration patterns [2]. Chronic Chagas cardiomyopathy is a progressive condition that mimics idiopathic DCM, with patients frequently presenting conduction abnormalities, arrhythmias, and ventricular dysfunction. The presence of Chagas disease in immunosuppressed individuals, including those undergoing chemotherapy, raises concerns regarding reactivation, which can accelerate myocardial deterioration and lead to life-threatening complications [3].

Anthracyclines, such as doxorubicin, have been the cornerstone of chemotherapy regimens for hematologic malignancies, including diffuse large B-cell lymphoma. However, despite their efficacy, these drugs carry the risk of cumulative dose-dependent cardiotoxicity, manifesting as left ventricular dysfunction and heart failure. The mechanisms underlying anthracycline-induced cardiomyopathy involve oxidative stress, mitochondrial dysfunction, and cardiomyocyte apoptosis, which contribute to the progressive decline in cardiac function [4]. In regions where Chagas disease is endemic, distinguishing between anthracycline-induced cardiomyopathy and Chagas cardiomyopathy can be particularly challenging. Both conditions share similar clinical and echocardiographic features, making serological and molecular testing crucial for accurate diagnosis. Furthermore, managing these patients requires a multidisciplinary approach, integrating oncologic, cardiologic, and infectious disease expertise to optimize treatment outcomes and mitigate cardiovascular risks [5].

This case report highlights the diagnostic challenges and clinical implications of DCM in a patient undergoing anthracycline chemotherapy in a tropical setting. It underscores the importance of preemptive screening for infectious diseases, early cardiac monitoring, and tailored therapeutic interventions to prevent adverse outcomes in high-risk populations. Dilated cardiomyopathy (DCM) is a severe and often irreversible complication of anthracycline chemotherapy. In tropical regions, Chagas disease may also be an underlying cause of DCM [1]. This case highlights the importance of differential diagnosis in this context.

Patient and observation     

Patient information: a 56-year-old male, originally from Brazil and an illegal gold miner, was admitted for general health deterioration associated with multiple lymphadenopathies. He reported significant weight loss (>10 kg in three months) and night sweats.

Clinical findings: on examination, the patient presented with a performance status of 2 (WHO scale), generalized lymphadenopathy (cervical, axillary, and inguinal), and no signs of systemic infection. Cardiovascular examination was unremarkable at admission.

Diagnostic assessment: a biopsy of the left inguinal lymph node confirmed diffuse large B-cell lymphoma. Pre-therapeutic viral serologies (HIV, HBV, HCV, HTLV-1) were negative. Echocardiography showed normal left ventricular dimensions (LVEDD= 50 mm), preserved systolic function (LVEF= 68%), and no valvular abnormalities.

Therapeutic intervention: the patient received six cycles of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone). Mid-treatment imaging revealed a partial response, allowing for treatment continuation.

Follow-up and outcomes: after the sixth cycle, the patient was admitted for acute dyspnea and hemoptysis. Computed tomography angiography ruled out pulmonary embolism but revealed cardiomegaly and bilateral pleural effusion. Echocardiography (ECG) showed sinus tachycardia, a newly developed right bundle branch block, and first-degree atrioventricular block. Echocardiography demonstrated severe left ventricular dysfunction (LVEF = 30%) with global hypokinesia and severe functional mitral regurgitation. Empirical treatment with intravenous diuretics and nitrates improved symptoms. Despite a cumulative doxorubicin dose of only 300 mg/m², anthracycline cardiotoxicity was initially suspected [2]. However, PCR analysis of pleural fluid later confirmed Trypanosoma cruzi infection. Subsequent serology on pre-chemotherapy blood samples confirmed chronic Chagas disease [3]. Benznidazole (5 mg/kg/day for 60 days) was initiated, leading to partial LVEF recovery (46%) and improved functional status with optimal heart failure therapy.

Patient perspective: the patient was informed of the dual etiology of his cardiac condition and the need for long-term follow-up. He expressed gratitude for the comprehensive management and showed adherence to heart failure therapy and antiparasitic treatment.

Informed consent: written informed consent was obtained from the patient for publication of this case report. The patient explicitly agreed to share his case details while maintaining anonymity.

Discussion     

This case underscores the complexity of diagnosing dilated cardiomyopathy (DCM) in an immunocompromised patient undergoing anthracycline chemotherapy. While anthracycline-induced cardiotoxicity is a well-known complication [4], its coexistence with Chagas disease represents a unique challenge in tropical settings. The cardiotoxic effects of anthracyclines are dose-dependent and often manifest as irreversible cardiac dysfunction [5]. In this case, despite a cumulative doxorubicin dose lower than the threshold commonly associated with cardiotoxicity, severe left ventricular dysfunction developed, prompting further investigation.

Chagas disease, caused by Trypanosoma cruzi, remains a major health concern in endemic regions [6]. Chronic Chagas cardiomyopathy can present with ventricular dilation, conduction disturbances, and heart failure. Immunosuppressive therapy, such as chemotherapy, can lead to reactivation of latent infections, exacerbating myocardial damage [7]. The presence of T. cruzi DNA in pleural fluid, confirmed by PCR, along with serological evidence of prior infection, strongly suggests reactivation in our patient. Reactivation of Chagas disease in immunosuppressed patients is a well-documented phenomenon, frequently leading to severe cardiac and systemic complications [8]. The partial improvement in left ventricular ejection fraction (LVEF) following benznidazole therapy highlights the potential benefit of early antiparasitic treatment in cases of Chagas reactivation [9]. While anthracycline-induced DCM is typically considered irreversible, the observed functional recovery suggests that parasite-related myocardial inflammation may have played a role in the deterioration of cardiac function.

This case underscores the need for systematic screening for endemic infections in patients undergoing chemotherapy in tropical regions. Routine pre-chemotherapy serological screening for T. cruzi could have enabled earlier intervention, potentially mitigating cardiac complications. Furthermore, cardiological monitoring, including baseline and follow-up echocardiography, should be mandatory for patients receiving anthracycline-based regimens, particularly those with additional risk factors for cardiomyopathy [10].

Conclusion     

DCM in patients undergoing anthracycline chemotherapy should always prompt a comprehensive etiological evaluation, especially in tropical regions where infectious diseases like Chagas disease are prevalent. This case highlights the importance of preemptive screening, early diagnosis, and integrated management strategies to improve patient outcomes. Multidisciplinary collaboration between oncologists, cardiologists, and infectious disease specialists is crucial in managing such complex cases effectively.

Competing interests     

The authors declare no competing interests.

Authors' contributions     

All the authors have read and agreed to the final version of this manuscript.

References