Endocardial fibroelastosis (EFE) is a term that may sound complex, but understanding it is crucial for deciphering some cardiac dysfunctions. For decades, it was considered a mysterious disease, often striking infants and young children. However, thanks to advancing research, we now know that EFE is not a disease itself, but rather a reaction of the heart's inner lining to various forms of stress, with viral infections being a significant underlying cause. This article will demystify EFE, explore its historical understanding, and highlight the critical role of viruses in its development.

What exactly is Endocardial Fibroelastosis (EFE)?

Imagine the inner surface of your heart, the endocardium, as a smooth, transparent lining that typically appears pink because the colour of the heart muscle is visible through it. In cases of EFE, this lining becomes thickened by layers of collagenous and elastic fibres, appearing opaque or pearly white, particularly in the ventricles. This thickening can cause the endocardium in the right ventricle to become over 10 micrometres thick, and in the left ventricle, over 20 micrometres thick.

The EFE reaction is almost always found in hearts that are under stress and typically affects the chamber experiencing the most strain, which is often the left ventricle. This stress can arise from various conditions, including infections, congenital malformations, or muscle diseases. The most rapid and severe cases of EFE are usually identified during fetal development and early infancy, periods of rapid heart growth, and sadly, these are also the times when patients are most at risk.

From mystery to mechanism: A shifting understanding

For a long time, medical professionals were puzzled by conditions that presented as an enlarged, failing heart in infants without an obvious cause. Pathologists in the early 20th century often grouped such conditions under broad, often vague names like "idiopathic cardiac hypertrophy" or "cardiac enlargement of indeterminate cause". It wasn't until 1943 that pathologists at Sinai Hospital of Baltimore coined the term "endocardial fibroelastosis" to describe the pearly white, microscopically layered endocardium they observed in these infants. This term quickly became widely accepted, synonymous with a dilated, failing infant heart when no other cause was apparent, even though it was initially diagnosed during life without definitive proof.¹

However, as more evidence emerged in the following decades, the concept of EFE as a standalone disease was challenged. In 1957, Black-Schaffer proposed a mechanical explanation: that stress on the ventricle directly causes this endocardial reaction, a concept that has since been confirmed by years of research. This fundamental shift in understanding, recognising EFE as a reaction rather than a disease, paved the way for identifying its numerous underlying causes.

The viral connection: Mumps, coxsackie, and adenovirus

Among the many factors that can trigger the EFE reaction, viral infections have been identified as particularly significant.²

Coxsackie virus

The Early Link In 1962, a landmark report by Fruhling and colleagues from the University of Strasbourg provided strong evidence linking the Coxsackie virus to EFE.¹ They observed epidemics of Coxsackie virus in eastern France that were consistently followed by an increase in EFE cases. Critically, they were able to recover the virus from the hearts or other organs of affected patients from autopsy tissue. Their pathological studies showed a progression: from initial myocarditis (inflammation of the heart muscle), to an intermediate state with both myocarditis and EFE, finally leaving only the endocardial deposits as the inflammation subsided. These findings were later supported by other studies.

Mumps virus

A Fulfilled Postulate: The story of the mumps virus and EFE is equally compelling. In 1963, Noren and associates linked EFE in surviving patients to a history of maternal mumps or mumps exposure during pregnancy.¹ While initially met with controversy, subsequent research strengthened this connection. Notably, virologist St. Geme (an associate of Noren) conducted experiments where the mumps virus was injected into embryonated hens' eggs. The hearts of the resulting chicks showed a progression from acute myocarditis to typical EFE over a year.

The widespread use of the mumps vaccine led to a dramatic reduction in new EFE cases, providing powerful indirect evidence.³ Further molecular work in 1997 by Jeffrey Towbin’s laboratory provided the definitive proof. By studying preserved EFE hearts from an era when mumps was prevalent, they detected mumps viral genome in a majority of the samples, effectively fulfilling Koch's postulates for establishing mumps as an etiologic agent of the EFE reaction.¹

A warning for today 

Despite the success of vaccines, vigilance is crucial. Recent mumps epidemics have occurred in regions like England and Wales (2004-2005) and the United States (2006), largely affecting young adults who may not have been immunised or received an ineffective vaccine. The offspring of these young adults are now considered at risk for developing EFE, underscoring the ongoing relevance of this viral connection.

Adenovirus and other pathogens

Beyond mumps and Coxsackie, other viruses like adenovirus have also been linked to myocarditis that can lead to EFE. Bacterial infections, such as Lactobacillus endocarditis, have also been reported in association with EFE.⁴ This reinforces the idea that various infectious agents can stress the heart and trigger the endocardial reaction.

How does infection lead to EFE?

While the exact biochemical pathways are complex, the basic mechanism involves the heart's response to stress. When a viral infection stresses the heart, particularly the smooth muscle cells within the endocardium, these cells begin to proliferate. They transform and migrate, producing an excess of elastin and collagen fibres. This accumulation of fibres leads to the characteristic thickening of the endocardium seen in EFE. This process is most active during periods of rapid growth, such as fetal development and early infancy.¹

Researchers often draw analogies to conditions like pulmonary hypertension, where similar smooth muscle cell proliferation and fibre production occur in response to stress in blood vessels. This suggests a complex network of signalling molecules, influenced by both environmental stressors (like viruses) and potentially genetic variations, in determining why some individuals develop EFE while others don't.¹

Why accurate terminology matters

It's vital for ongoing research and clinical practice to understand that EFE is a reaction, a secondary feature, not a primary disease entity. Referring to it as a "disease" or using outdated terms like "primary endocardial fibroelastosis" (which implies no known cause) can hinder accurate diagnosis, treatment, and scientific progress. Instead, when the cause is unknown, "idiopathic endocardial fibroelastosis" is the more appropriate term.¹ Modern classification systems, like the North American Pediatric Cardiomyopathy Registry, treat EFE as a "modifying characteristic" of an underlying cardiomyopathy, rather than a separate disease.

By using precise language, we ensure that clinicians and researchers focus on identifying and treating the underlying cause, whether it's a viral infection, a genetic condition, or another form of cardiac stress.

Conclusion

The journey from viewing Endocardial Fibroelastosis as a mysterious disease to understanding it as a reaction to underlying cardiac stress, particularly from viral infections, represents a significant advance in cardiology. The roles of mumps, Coxsackie, and adenovirus are well-established, highlighting the profound impact of infectious agents on heart development and health. As we witness resurgences of vaccine-preventable diseases like mumps, it serves as a crucial reminder for vigilance in public health and continued research into the intricate mechanisms of heart disease. Recognising EFE as a reaction, rather than a standalone illness, is fundamental to better diagnosis, treatment, and ultimately, healthier hearts for the youngest and most vulnerable among us.

Summary

Endocardial fibroelastosis (EFE) is the thickening of the heart's inner lining (endocardium) by collagen and elastic fibres. It is now understood to be a reaction to various forms of stress on the heart, not a disease itself. Viral infections play a significant role as an underlying cause, with strong evidence linking Coxsackie virus and especially the mumps virus to EFE development. The widespread mumps vaccine led to a sharp decline in EFE cases, but recent mumps epidemics raise concerns about future occurrences. Other stressors, including genetic conditions and congenital malformations, can also trigger EFE. Accurate terminology is vital, as referring to EFE as a disease delays understanding and progress.

Frequently Asked Questions (FAQs)

What is Endocardial Fibroelastosis (EFE)?

EFE is a condition where the inner lining of the heart, called the endocardium, becomes abnormally thickened with layers of collagen and elastic fibres. Normally, the endocardium is thin and transparent, but with EFE, it appears opaque or pearly white.

Is EFE a disease on its own?

No, EFE is not considered a disease itself. Instead, it is a "reaction" of the endocardium to an underlying stress or disease affecting the heart. It's a secondary feature that can be associated with many different conditions.

What viral infections are known to cause EFE?

The Coxsackie virus and the mumps virus have been clearly established as causes of EFE. Adenovirus is also listed as a viral cause of myocarditis (heart muscle inflammation) that can be associated with EFE.