Introduction

Heart enlargement, or also cardiomegaly, is a medical condition in which the heart is bigger than an average human’s heart. An enlarged heart implies that the heart, or a portion of it, may have grown thicker or stretched out. The cause of this condition varies across individuals; although genetics, family history, and lifestyle environmental factors may increase the chance of an enlarged heart developing. Numerous acquired disorders that affect the heart muscle (referred as cardiomyopathies) can also present with heart enlargement. Because the heart would have to work twice as hard to pump the blood effectively, this could result in an irregular blood flow pattern, and develop into cardiac failure or hypertension if left untreated.¹

With the recent advancement in technology, biomarkers can be used to monitor the progression of heart enlargement. A biomarker is a specific biological molecule, such as a protein or a hormone, that is present in the blood, tissues, or bodily fluids. and can be measured in the body, to provide information about a person's health. To elaborate, we can identify genetic abnormalities through biomarkers, which may reveal whether an individual may be at risk of contracting specific illnesses, or determine how successfully an illness or a condition is being treated in the body. 

Blood biomarkers are increasingly utilised due to its nature of being more accessible, accurate, and cost-effective in comparison to other biomarkers.² By observing the development of heart enlargement, we can gain an insight to any diseases that may have caused heart enlargement, or was developed from this condition, to ensure more immediate treatment. 

Key blood biomarkers 

Natriuretic peptides 

Natriuretic peptides (NPs) are a type of hormone/paracrine factors present in your heart and blood vessels, and form the natriuretic peptide system (NPS). The NPS promotes cell growth, regulating fluid and any inflammatory processes, and balancing electrolytes. This system comprises several peptides, including the atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and the N-Terminal fragment of BNP (NT-pro-BNP). 

When the heart chambers experience an increased in the amount of pressure, which is frequently brought on by conditions such as heart failure, ANP and BNP are released in the bloodstream. BNP is produced in the ventricles when the heart experiences strain from an increased wall tension or stretching. However, ANP is released from the atria in reaction to a high blood volume or pressure. Both of these peptides cooperate together to maintain the dilation or widening of your veins and arteries, thereby ensuring an easier blood flow and  any blood clots from occurring. NPs are also found in the kidneys, and are able to encourage salt and fluid excretion to lower blood pressure. As a result, the heart attempts to lessen a volume overload, which is reflected in elevated levels of these peptides.³

BNP and its precursor, NT-proBNP, are particularly useful at being consistently quantified in blood. The information helps to determine cardiac stress caused by heart enlargement and the overall heart function. The amount of the BNP in your blood is determined by a blood test; a high level of this peptide indicates that the heart is overworking to pump blood, which can lead to problems without any intervention.⁴

Not only does the BNF test aid doctors in ruling out any other health conditions, but it allows your healthcare provider to map out appropriate treatments in accordance to the size and state of the heart. 

Troponins

Troponin is a type of protein that is localised in several of your muscles, including your heart muscle. It plays a critical role for the contraction of your heart - to put it in other terms, it facilitates heartbeats. Troponin is normally found in low concentration in the blood; however, if your heart muscle is injured or damaged from a heart attack and is unable to receive oxygen-rich blood, a portion of this protein is correspondingly released from the muscles into your bloodstream.⁵ The amount of troponin released depends on the extent of the heart’s injury.

Although troponins are primarily known for detecting acute myocardial injury, troponin levels also rise in chronic heart conditions, indicating ongoing stress or micro-injury within an enlarging heart. Troponin testing helps monitor disease progression by identifying subtle heart damage early, allowing for targeted interventions.⁶

Galectin-3

Galectins are carbohydrate-binding proteins that are expressed by immune cells, and play an important role in tissue repair, inflammation, and in cellular functions (i.e. cell repair and growth). Research has demonstrated that one of its subgroups, galectin-3 (Gal-3), is frequently detected in various diseases - including heart disease. Gal-3 can be employed as a sensitive diagnostic or prognostic biomarker since it is easily released from wounded and inflammatory cells to the cell surface and into bodily fluids (such as serum and urine).

Depending on the underlying causes of heart failure, clinical studies indicate that serum and myocardial (the middle muscular layer of the heart wall) Gal-3 levels in patients with heart failure represent cardiac inflammatory conditions. Even more so, Gal-3 can be regarded as a suitable biomarker for both cardiac inflammation and fibrosis. Fibrosis refers to the thickening of tissues.⁷ A high plasma Gal-3 content is associated with heart failure clinical outcomes in the general population. Both patients with short-term and long-term heart failure, with preserved or reduced ejection fraction, have negative clinical outcomes linked to elevated serum levels of Gal-3.⁸

In other words, we can use Gal-3 levels to monitor structural changes in the heart’s size and shape (also known as cardiac remodelling). 

Soluble ST2 (sST2)

As a member of the interleukin-1 receptor family, soluble ST2 is produced in reaction to fibrosis, inflammation, and cardiac stress. Elevated sST2 levels are linked to ventricular strain and remodelling, both of which are important contributors in the pathogenesis of heart enlargement. SST2 levels increase with worsening heart enlargement, suggesting elevated cardiac stress and possible structural alterations. Tracking sST2 levels over time allows healthcare providers to adjust treatments, aiming to slow or reverse the enlargement process.⁹

Growth differentiation factor-15 (GDF-15)

The growth differentiation factor-15 (GDF-15) is a type of cytokine that targets inflammation and is involved in key cellular functions. Studies have found that patients with an elevated level of GDF-15 in the blood are associated with a higher risk of cardiovascular disease development in the general population. This suggests detrimental structural alterations in the heart.¹⁰ By triggering prompt therapeutic modifications to stop deteriorating cardiac problems, GDF-15’s presence in the blood acts as a significant predictive marker for the progression and complications of the disease., GDF-15 also helps with early diagnosis and management of heart enlargement.

Summary

Heart enlargement is a condition characterised by a heart that is bigger than the average heart. We can use distinct biomarkers, such as BNP, troponins, Gal-3 ssT2, and GDF-15 to effectively monitor the progression of heart enlargement, to prevent the worsening state of the heart. 

Biomarkers help to detect any early signs of heart failure, due to the heart having to work twice as hard when it is stretched out from its enlarged condition. As a result, doctors are able to determine and predict any long-term outcomes, as well as personalising treatment plans to ensure better management.