Unveiling Endomyocardial Fibrosis (EMF): Diagnosis and Evaluation

Endomyocardial fibrosis (EMF), also known as Loffler and Davies disease, is a mysterious heart condition characterized by fibrosis in the heart's chambers, leading to severe damage and valve issues. It primarily affects impoverished communities in tropical Africa, where diagnostic tools and medical care are scarce.(1)

The disease's progression involves inflammation, necrosis, thrombosis, and eventually fibrosis. The exact cause remains unclear, with factors such as ethnicity, diet, poverty, infection, and eosinophilia playing potential roles. Although cerium and malnutrition have been considered, their direct link to EMF is unconfirmed. Parasites like microfilaria and malaria are associated with EMF, suggesting their involvement in its pathogenesis.(2)

Diagnosing endomyocardial fibrosis can be challenging due to its rarity and the lack of standard diagnostic criteria. However, there are key clinical and imaging methods that can aid in its identification.(3)

Advancements in diagnosing endomyocardial fibrosis

Traditionally, researchers relied on post-mortem examinations and angiography for diagnosing EMF. However, recent advancements in diagnostic methods, such as echocardiography and cardiac magnetic resonance (CMR), have significantly improved the accuracy of EMF diagnosis. Mocumbi and colleagues have introduced a scoring system to assess EMF severity. The scoring system is more effective in population-based surveys where early disease stages can be detected.(2)

      I.          Clinical Stages of EMF

The early symptoms of EMF are often nonspecific and can resemble febrile illnesses, including lymphadenopathy and occasionally splenomegaly. This similarity often leads to provisional diagnoses of malaria, which is prevalent in the same regions as EMF. Unfortunately, EMF becomes more apparent in its advanced stages of heart failure. Alderman described the disease's initial clinical presentation and stages:

·       The necrotic stage with fever and lymphadenopathy

·       The thrombotic stage with thrombotic emboli and splinter haemorrhages

·       The fibrotic stage characterized by restrictive myopathy

Most EMF patients are diagnosed late, presenting with advanced heart failure, gross ascites, anorexia, weight loss, and occasional chest pain. Tense ascites is a common feature in EMF cases, and it is often associated with mild or no oedema, reflecting a systemic impact of the disease.(2)

    II.          Cardiac findings in EMF from ECG and chest X-ray

Electrocardiogram (ECG) and chest X-ray findings play a crucial role in diagnosing EMF, although they often lack specificity.(3)

·       ECG: This usually reveals non-specific abnormalities. Sinus tachycardia is observed in approximately 22% of cases, while 43% show signs of atrial abnormality. First-degree heart block is identified in 39% of patients, and atrial fibrillation is present in 13%. However, these findings are not exclusive to EMF, making it challenging to rely solely on them for diagnosis.

·       Chest X-rays: This tends to display non-specific features. Cardiomegaly, an enlargement of the heart, is a common finding in EMF patients. Additionally, pericardial effusion, the accumulation of fluid around the heart, is present in 87% of cases. Though, they do not provide a definitive diagnosis of EMF.

 III.          Haemotalogical investigations

·       Iron deficiency anaemia is a common feature in EMF patients, with haemoglobin levels as low as 5g/dL and depleted iron stores.

·       Absolute eosinophilia is not typically seen in patients who present late with heart failure. High eosinophil counts characterize the early phases of the disease.

·      Leukocytosis, an increase in white blood cells, is not a prominent feature of EMF.

·       Hypomagnesemia has been reported in several EMF patients. This condition has been considered a potential risk factor when combined with Cerium, an element found in diets rich in tubers.(4)

 IV.          Echocardiography as a key diagnostic tool (1)

Echocardiography has emerged as the gold standard tool for diagnosing EMF. This diagnostic method involves examining the heart from various angles using five standard echocardiographic views:

• Parasternal long axis (PLX)
• Short axis (SX)
• Apical four chambers (AP4)
• Apical long-axis (APLX)
• Apical two chambers (AP2)

Five primary diagnostic echocardiographic features of EMF are commonly observed together:

·       Apical fibrosis

·       Ventricular wall fibrosis

·       Significant atrial enlargement

·       Atrioventricular valve regurgitation

·       Obliteration of the ventricular cavity

The second group of features, though not present in all patients, can provide further confirmation of the diagnosis. These include:

·       Pericardial effusion

·       Formation of an endocardial fibrous shelf (EFS) which extends into the posterior left ventricular wall recess and engulfs the posterior mitral valve leaflet.

Furthermore, the presence of pericardial calcification has been noted, leading to a form of constrictive pericarditis known as endomyocardiopericarial fibrosis (EMPF). Three echocardiographic types of EMF have been recognized:

·       Left ventricular (53%)

·       Right ventricular (18%)

·       Biventricular (29%)

These echocardiographic findings correlate well with intraoperative and postmortem findings, including the three layers within the myocardium, the formation of a line of cleavage utilized in surgical procedures, and the characteristic enlargement of the atria.

    V.          Cardiac magnetic resonance

CMR has taken precedence over cardiac catheterization as the primary diagnostic tool for EMF. CMR employs various imaging techniques, including cine imaging, first-pass contrast-enhanced perfusion, and Late Gadolinium Enhancement (LGE), to identify the presence of EMF. Through CMR, physicians can visualize critical diagnostic features of EMF, such as the obliteration of the ventricle, apical dimples, thrombi, grossly dilated atria, and regurgitant atrioventricular valves. Furthermore, CMR images commonly reveal pericardial effusion and ascites, characteristic findings in EMF cases.(1)

 VI.          Cardiac catheterisation

Cardiac catheterization plays a crucial role in EMF patients, particularly in procedures like excision biopsy of the endocardium. Histological examination of EMF reveals distinctive features, including:

·       Reactive fibrosis

·       Deposition of type-1 collagen

·       Subendocardial infarction

·       Eosinophil infiltration in the upper myocardium

·       Thrombus formation

·        Mild inflammatory infiltrates, primarily composed of lymphocytes, are frequent

Cardiac catheterization offers the opportunity for direct sampling of endocardial tissue, allowing for precise histological assessment and contributing to our understanding of EMF's underlying pathological processes.(2)

Conclusion

The diagnosis of EMF relies on advanced imaging techniques, notably echocardiography and cardiac magnetic resonance. These tools reveal characteristic features such as apical fibrosis, ventricular wall fibrosis, atrial enlargement, valve regurgitation, and ventricular obliteration. Cardiac catheterization can offer histological insights. Early diagnosis is critical to improve the management of this enigmatic and often devastating cardiac condition.

Cover Image Credit: 

M. P. M. Graham-Brown, A. S. Patel, D. J. Stensel, D. S. March, A.-M. Marsh, J. McAdam, G. P. McCann, J. O. Burton, "Imaging of Myocardial Fibrosis in Patients with End-Stage Renal Disease: Current Limitations and Future Possibilities", BioMed Research International, vol. 2017, Article ID 5453606, 14 pages, 2017. https://doi.org/10.1155/2017/5453606

References

1.         Khalil SI. Endomyocardial Fibrosis: Diagnosis and Management. JVD. 2020 Feb;Volume 8:1–9.

2.         Duraes AR, de Souza Lima Bitar Y, Roever L, Neto MG. Endomyocardial fibrosis: past, present, and future. Heart Fail Rev. 2020 Sep;25(5):725–30.

3.         de Carvalho FP, Azevedo CF. Comprehensive Assessment of Endomyocardial Fibrosis with Cardiac MRI: Morphology, Function, and Tissue Characterization. RadioGraphics. 2020 Mar;40(2):336–53.

4.         Grimaldi A, Mocumbi AO, Freers J, Lachaud M, Mirabel M, Ferreira B, et al. Tropical Endomyocardial Fibrosis: Natural History, Challenges, and Perspectives. Circulation. 2016 Jun 14;133(24):2503–15.

What is the gold standard tool for the diagnosis of endomyocardial fibrosis?

1. Echocardiography
2. Cardiac catheterization
3. Cardiac magnetic resonance
4. Electrocardiography