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No potential conflict of interest relevant to this article was reported.
Editor responsible for the review: Claudio Tinoco Mesquita
Chagas disease (CD) is a neglected tropical disease (NTD) caused by
Chagas disease (CD), caused by
The main transmission route in endemic zones is vectorial, although the non-vectorial ways including blood transfusion, mother-to-child, food-borne, contamination and organ transplantation should also be considered.
CD is diagnosed by epidemiologic history and two positive serological tests. The infection has two main clinical phases: acute and chronic. Approximately 70% to 80% of individuals with chronic CD remain asymptomatic, while 20% to 30% develop cardiac and/or gastrointestinal disease.
The electrocardiogram (ECG) is the first diagnostic tool to consider for clinical diagnosis since the earliest signs of cardiac CD (CCD) are generally conduction system disorders and/or ventricular arrhythmias. In addition, the different cardiac imaging modalities: chest X-ray, echocardiography, nuclear medicine, computed tomography (CT), and cardiac magnetic resonance (CMR) play an essential role in the diagnosis and management of CD. Thus, in the present multimodality imaging era, and considering that CCD is a NTD, more prevalent in low-and-middle income countries (LMICs) with limited resources, it is mandatory to wisely use the different imaging tools in the best possible way, considering the characteristics of the individual patient.
To harness the full potential of medical imaging for the effective management of patients with CD, a comprehensive approach is essential. This involves a concerted effort to invest in the education of medical providers. Moreover, facilitating widespread access to diagnostic tools, particularly medical imaging modalities, is imperative. Accessible and timely diagnosis is crucial for providing prompt and targeted interventions, thereby enhancing patient outcomes. Finally, continuous investment in research is vital to advance our understanding of CD, refine imaging modalities and develop innovative solutions for improved patient care.
In this review of the literature, we summarize the main characteristics of CCD regarding epidemiology, pathophysiology and clinical presentation. We also review the indications, advantages, and limitations of cardiac imaging techniques in these patients. We further present some clinical cases where cardiac imaging proved helpful in patients with CCD.
We conducted a narrative review of articles on CD published on PubMed, SciELO, NCBI, Science Direct, and Embase databases over the last 20 years.
Although CD is endemic to Central and South America, patients are also living in non-endemic zones. It has been estimated that around 6–8 million people are infected globally, 65–100 million are at risk of infection, and there are 28,000 new cases annually.
Regarding the economic impact of CD, Lee et al.
The loss of DALYs and the socioeconomic impact of CD are caused by incomplete diagnosis and clinical follow-up; lack of funding and access to health care; insufficient knowledge about CD by primary care physicians and even by cardiologists from non-endemic countries; shortage of financial resources for education and research; as well as inadequate diagnostic tools and treatment.
The pathophysiology of the cardiac damage in CD is complex and involves several mechanisms that lead to inflammation, cell death and fibrosis, including damage to the conduction tissue and categorized into: 1) parasite persistence-dependent myocardial damage, with related myocarditis; 2) parasite-driven adverse immune response; 3) neurogenic disorders, and 4) microvascular disturbances causing myocardial ischemia with normal epicardial coronary arteries.
The risk of sudden cardiac death (SCD) in CCD patients is increased by the presence of severe ventricular dysfunction and malignant ventricular arrhythmias.
CD presents in three clinical phases: acute, indeterminate (or chronic without overt disease), and chronic.
Generally, the acute phase resolves spontaneously in few weeks or months. Sixty to seventy percent of patients may be cured with early specific antiparasitic treatment.
Less than half of patients develop the cardiac and/or gastrointestinal involvement that characterizes the chronic stage of CD years after the acute and indeterminate phases, with unnoticeable parasitemia levels. Genetic predisposition, geographical area (endemic areas), type of infection, immunosuppression status, concomitant chronic diseases, and other factors like age, male sex, alcoholism, persistence of high parasitemia, and severity of the disease in the acute phase have been associated with disease progression.
To identify predictors of the development of cardiac and digestive disorders in CD, Nunes da Costa et al.
Chronic Chagas cardiomyopathy (CCCM) affects approximately 20-30% of infected individuals.
According to the Latin American guidelines for diagnosing and treating Chagas heart disease (
ECG: electrocardiogram; HF: heart failure; LV: left ventricular
Stage
Findings
A
Normal ECG, no heart disease, symptoms or structural disorder
B1
Asymptomatic with ECG changes and no LV dysfunction
B2
Asymptomatic with LV dysfunction but no symptoms of HF
C
LV dysfunction and current or previous symptoms of HF
D
Refractory symptoms of HF at rest despite optimal therapy, requiring specialized and intensive interventions
CCCM is characterized by more intense and extensive inflammation and fibrosis, autonomic dysfunction, higher frequency of atrioventricular and intraventricular blockage, multifocal ventricular extrasystoles. It is also marked by autoimmunity with production of antibodies against myocytes, beta-adrenergic receptors, and neurons, in comparison with other dilated cardiomyopathies.
Atypical angina pectoris, often unrelated to exertion and unresponsive to nitrates, is common in patients with CCD. This occurs even in the presence of transient or definite ST-T changes on ECG, abnormal Q waves, and segmental LV wall motion abnormalities, mimicking coronary artery disease (CAD). However, there is no significant epicardial obstructive CAD. Microvascular disturbances and inflammation have been suggested as possible explanations.
Patients with Chagas heart disease have a worse prognosis than other cardiomyopathies. Male gender has been associated with higher mortality rates.
Diagnosis of CD is made by detecting the parasite in the acute phase, with high levels of parasitemia by one of three methods: direct (confirmation of the presence of
In the chronic phase, parasitemia is low and, consequently, the most effective diagnostic methods involve identifying antibodies against the etiologic agent. At least two serological methods must be used to confirm the diagnosis. The most used are enzyme-linked immunosorbent assay, indirect immunofluorescence, and indirect hemagglutination.
Chagas cardiomyopathy is usually considered a dilated cardiomyopathy. However, the typical distribution of fibrosis to the LV posterior, apicolateral, and apical regions, and the involvement of the sinus node and electric conduction system help distinguish it from other cardiomyopathies.
The more frequent ECG alterations are RBBB, left anterior fascicle block (LAFB), non-sustained ventricular tachycardia (VT), atrioventricular block of variable degree, sinus bradycardia, atrial fibrillation (AF), and changes in the ST segment and T-wave.
When available, 24-h Holter monitoring is recommended in the first evaluation of all patients with the cardiac form of CD and whenever new symptoms suggestive of cardiac arrhythmias appear. This recording helps to detect an increased risk of SCD and unmask signs of autonomic dysfunction, such as a reduced heart rate variability.
Cardiomegaly with enlargement of the right and left heart chambers may appear in advanced stages of CD, but pulmonary congestion is usually mild or absent.
When available, an exercise test should be performed to detect ventricular arrhythmias, assess functional capacity, and evaluate the autonomic dysfunction through the chronotropic response and heart rate in the first minute of recovery. It is also possible to assess ST changes in differential diagnosis in patients with chest pain to exclude CAD.
The echocardiogram is the most used imaging modality for diagnosing and following-up CD patients due to its wide availability and information on ventricular function. Three-dimensional echocardiography can quantify LV volumes and function more accurately, as no geometric assumptions are required. Regional strain is beneficial in CCD due to the segmental myocardial pattern of damage, mainly for recognition of subclinical myocardial dysfunction during the indeterminate phase.
Segmental wall motion abnormalities (from hypokinesia to aneurysm formation) can be seen since the early stages of the chronic phase, mainly in the apex and in basal segments of the inferior and inferolateral wall.
The “Recommendations for Multimodality Cardiac Imaging in patients with CD: A Report from the American Society of Echocardiography in Collaboration With the InterAmerican Association of Echocardiography (ECOSIAC) and the Cardiovascular Imaging Department of the Brazilian Society of Cardiology (DIC-SBC)”,
ECG and echocardiogram should be performed as part of the initial evaluation of all patients with newly diagnosed CD to exclude LV dysfunction, aneurysms, and conduction abnormalities or arrhythmias;
ECG follow-up is reasonable every two to five years in the indeterminate form.
Echocardiography should be performed if any changes in ECG findings or clinical condition suggesting possible HF are noted.
CMR provides very accurate and reproducible information of the LV and RV function, with high spatial resolution, and not dependent on geometric assumptions. It can identify myocardial fibrosis using late gadolinium enhancement (LGE). LV apical aneurysms can be detected in 20–28% of CCD patients on CMR, with no sex-based difference.
CMR allows to identify the consequences of inflammation due to cardiac cell injury caused by T. cruzi and its related immune reactions using T2-weighted and LGE sequences for detecting myocarditis.
Up to 20% of asymptomatic chronic-stage patients without LV segmental motion abnormalities have signs of fibrosis on CMR, whose extent relates to the severity of LV systolic dysfunction and the presence of ventricular arrhythmias,
Other findings throughout all phases of CCD are myocardial edema (increase in T2-weighted -T2W- myocardial signal intensity) and hyperemia (T1-weighted myocardial early gadolinium enhancement –MEGE),
CMR confirms the tendency for more extensive disease in men. Assunção et al.
Although myocardial fibrosis was similarly prevalent in female and male patients (87% vs. 71%, p = 0.21), the amount was significantly higher in males. Furthermore, in both sexes, fibrosis distribution was similarly frequent in lateral and inferior LV segments, but significantly higher in the septal and apical segments in male patients.
MUGA scan acquisition and processing are reproducible, providing more precise information on ventricular function in patients with CD than echo. In contrast to M-mode and 2D echo, MUGA averages hundreds of cardiac cycles and does not depend on geometric assumptions for LVEF calculation. In addition, it is possible to quantify RV function and to assess ventricular dyssynchrony.
In CCD, MPI with Single-Photon Emission Computed Tomography (SPECT) can show not only fixed perfusion defects, associated with areas of fibrosis and wall motion abnormality,
It is possible to assess intraventricular synchronism using phase analysis in gated SPECT MPI.
In a study of 36 patients with CCD assessed with stress-rest MPI SPECT initially and after a mean follow-up of 5.6 years, 20 (56 %) showed reversible myocardial perfusion defects.
Although most patients with CD have epicardial coronaries without significant lesions, cardiac catheterization may be necessary in some cases to rule out epicardial CAD, which could coexist with CD.
Abnormalities in sympathetic innervation constitute an early finding in CCD, preceding other cardiac changes in one-third of patients and can be associated with areas that will develop regional wall motion abnormalities and perfusion defects.
Miranda et al.
FDG-PET identifies areas of myocardial inflammation in patients with non-ischemic cardiomyopathies.
Some case reports have described increased uptake of
1Cardiac CT could be considered in three scenarios in CD patients
To exclude CAD in patients with low to intermediate pretest probability, due to its high negative predictive value.
In planning of complex electrophysiological procedures to avoid coronary arteries injuries during ablation.
To assess ventricular function and morphology if there are contraindications for CMR and poor acoustic windows for echo.
A proposal for an algorithm for diagnosing CCD is presented in
The leading cause of mortality in the chronic phase of CD is SCD, accounting for 50%-65% of deaths.
The Rassi score for patients with established CCD includes six factors (a combination of clinical symptoms, test results, and demographics) with weighted values to categorize patients by risk of 10-year mortality: low (10%), medium (44%), and high (84%).
Myocardial scar has been related to sustained VT, cardiovascular death, hospital admission for heart failure, heart transplantation, and appropriate implantable cardioverter-defibrillator therapy.
CD remains a largely neglected disease with insufficient diagnostic and therapeutic pathways. To properly face this health problem through a multidisciplinary, comprehensive, and timely approach, some points should be considered:
CD has long-term clinical repercussions and causes high care costs exacerbated by social and economic conditions of the inhabitants of LMICs in endemic areas. Therefore, research and investment in community prevention strategies (pharmacological or non-pharmacological) are important .
High-quality epidemiological research and investment in education are needed to improve the recognition and care of CD patients both in endemic and non-endemic areas.
The appropriate and efficient use of cardiac imaging is crucial to detect the cardiac involvement in patients with CD, as well as to stage the disease, stratify patient risk and address management with a personalized approach. Thus, investment in diagnostic methods and medical providers’ education is needed.
New biomarkers for early detection of the disease and monitoring of therapeutic efficacy are needed. These biomarkers will help to guide risk stratification and treatment guidelines.
The early mortality and substantial disability stemming from CD impose a considerable social and economic burden, particularly in the Latin America Andean region. The complex nature of Chagas heart disease underscores the critical role of cardiac imaging not only in detecting cardiac involvement but also in accurately staging the disease, stratifying patient risk, and guiding effective management strategies (
As we confront the challenges presented by Chagas heart disease, it becomes increasingly evident that investment in the education of medical providers is paramount. Providing healthcare professionals with the knowledge and skills to recognize, diagnose, and manage Chagas heart disease is fundamental to improve patient outcomes.
Furthermore, a comprehensive approach requires the development and implementation of accurate diagnostic methods, with a particular emphasis on advanced imaging techniques. These methods play a pivotal role in early detection and intervention, essential components in the effort to alleviate the burden imposed by Chagas heart disease.
Concomitantly, the urgency for investment in research persists. Advancements in understanding the pathophysiology, epidemiology, and treatment modalities are crucial for refining our approach to Chagas heart disease. Appropriate allocation of resources towards research initiatives will undoubtedly contribute to the development of innovative and effective strategies to combat this pervasive health challenge.
Study Association
This study is not associated with any thesis or dissertation work.
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This article does not contain any studies with human participants or animals performed by any of the authors.
Sources of Funding: There were no external funding sources for this study.