This systematic review compiled the available evidence on the association between parasitic infections and the development of endomyocardial fibrosis (EMF), based on 12 studies involving 16 patients. Despite the small sample size, the findings reveal relevant epidemiological, clinical, and diagnostic patterns, suggesting a possible causal or at least contributory role of certain parasitic infections, particularly Schistosoma mansoni, in the pathogenesis of EMF.
The predominance of Schistosoma mansoni (63%) among the identified parasites reflects the high prevalence of schistosomiasis in tropical and subtropical regions, from which most of the analyzed cases originated. A single case reported in France is likely an imported infection, underscoring the global mobility of parasitic diseases and the importance of considering travel history in diagnosis. Chronic schistosomal infection, particularly in its hepatosplenic form, may trigger persistent immune activation, portal hypertension, and eosinophilic infiltration. These mechanisms are likely contributors to the fibrotic remodeling of the endocardium [27, 28].
This study found that the mean age of affected males and females was in the early-to-mid 30s; previous studies report the first peak of EMF incidence in children and adolescents age 10 to 19 years, with a second peak occurring in the 30s [29, 30]. This discrepancy may reflect underreporting or misdiagnosis of EMF in younger populations, especially in low-resource settings where diagnostic capabilities are limited. Younger patients may also present with milder or nonspecific symptoms that are less likely to prompt detailed cardiac evaluation, contributing to their underrepresentation in published case reports. Additionally, it is possible that there is a genuine trend in the literature toward more frequent reporting of cases in the second peak, potentially due to increased recognition of EMF in adults or a bias toward publishing more complex or severe adult cases. This pattern suggests that both underreporting in children and a higher likelihood of reporting adult cases may have influenced the observed age distribution in this study.
The presence of eosinophilia in some cases suggests a potential eosinophil-mediated immune response, similar to that seen in Loeffler’s endocarditis and hypereosinophilic syndromes [31]. Other identified parasites, including S. haematobium, Wuchereria bancrofti, and Trypanosoma cruzi, have also been linked to cardiovascular manifestations [32, 33], indicating that a range of pathophysiological mechanisms may be involved, such as direct myocardial invasion, immune complex deposition, and chronic inflammation. The life cycle of Schistosoma species offers key insights into potential localized contributions to endomyocardial fibrosis (EMF). Adult worms lay eggs in the mesenteric or pelvic venous systems, which can traverse the inferior vena cava into the right heart and pulmonary circulation. While this migratory route is best known for contributing to pulmonary arterial hypertension (PAH) through the embolization of eggs into pulmonary arterioles, it may also facilitate local myocardial and endocardial injury relevant to EMF [34,35,36,37]. Experimental models have shown that schistosomal eggs lodged in lung vasculature trigger intense granulomatous inflammation, Th2-mediated cytokine release (IL‑4, IL‑13), and perivascular fibrosis, leading to persistent PAH [34]. Similar immune mechanisms, involving eosinophils, immune complexes, and TGF‑β signaling, may plausibly extend to the myocardium when eggs or antigenic debris reach the heart. Indeed, helminth-induced eosinophilic myocarditis and cardiac fibrosis have been documented, with eosinophil-derived proteins (e.g., major basic protein, eosinophilic cationic protein) causing endothelial and myocyte damage [38]. Therefore, the passage of schistosomal eggs through the inferior vena cava not only supports systemic immune activation, but may also provoke localized endocardial and myocardial inflammation. This localized inflammatory milieu, characterized by immune complex deposition, hypereosinophilia, and fibrotic cytokine release, could directly contribute to EMF pathogenesis. While systemic mechanisms remain central, the potential for local egg-induced endocardial injury enriches our understanding of how parasitic infection might drive fibrotic remodeling in the heart.
Clinical presentation varied across studies; however, recurring signs included fibrosis of the right ventricular endocardium (81%), dilated right atrium (75%), pericardial effusion (75%), bilateral lower limb edema (63%), and ascites (63%). The most frequently reported symptoms were abdominal distension (63%) and dyspnea (63%). Atrial thrombosis and atrial fibrillation, each reported in 38% of cases, were the most common complications. In several patients, abdominal distension and hepatosplenomegaly were observed, likely indicating systemic congestion or portal hypertension secondary to right-sided cardiac dysfunction [27, 28].
Thromboembolic events, such as ischemic stroke (13%) and pulmonary embolism (6%), were also reported, highlighting the need for vigilance regarding coagulation abnormalities in this patient population. Outcomes appeared more favorable in those who received a combination of antiparasitic and heart failure therapies. Nonetheless, a case fatality rate of 19%, primarily due to multi-organ failure and thromboembolic events, underscores the severity of EMF and the importance of early diagnosis and comprehensive, multidisciplinary management.
Echocardiography was the most commonly used diagnostic modality (92%), effectively identifying hallmark features of EMF such as ventricular obliteration, endocardial thickening, valvular dysfunction, and thrombus formation [34]. Additional imaging with cardiac MRI, CT, and histopathology was helpful in selected cases, particularly for evaluating fibrosis, calcification, or confirming eosinophilic infiltration.
Parasitological confirmation was achieved through the detection of Schistosoma haematobium by microscopy in a few cases; however, parasitological testing was inconsistently reported, and serological tests for parasite-specific antibodies were more frequently used.
This review has inherent limitations due to the nature of case reports and small case series, including publication bias, limited generalizability, and heterogeneity in diagnostic criteria and therapeutic approaches. The variability in clinical presentation, diagnostic workup, and treatment strategies precluded a meta-analysis and highlights the absence of standardized clinical guidelines for parasite-associated EMF. The temporal association and biological plausibility suggest a contributory role of parasitic infections; however, the possibility of other underlying factors influencing the development or progression of EMF cannot be entirely excluded.
Prospective studies in endemic regions are needed to clarify the causal mechanisms underlying this association. Furthermore, the development of standardized diagnostic algorithms and investigation of immunopathological pathways are essential to improve clinical recognition and patient outcomes. Incorporating parasitic screening in patients with unexplained restrictive cardiomyopathy or EMF, particularly in endemic areas, may allow for earlier diagnosis and targeted treatment.
