Introduction

Heart enlargement (cardiomegaly) is a life-threatening condition that should not be underestimated or left untreated. ‘Cardiomegaly’ is an umbrella term used to define an enlarged heart, derived from ‘cardio’, meaning heart, and ‘-megaly’, indicating an increase in size. The enlargement can be observed in the left or right ventricles or the atria.¹ 

Understanding cardiomegaly

 Cardiomegaly is a condition that often remains undetected until symptoms such as fatigue and shortness of breath begin to appear. However, the cases diagnosed are on the rise. It is typically an outcome of other underlying disorders that affect the heart muscle function.¹ As a result of these underlying conditions, the heart cannot supply adequate amounts of blood to the whole body. In order to increase the cardiac output, which is the amount of blood your heart pumps per minute, the body activates many compensatory mechanisms, one of which is enlarging the heart to maintain enough blood flow to the body.² 

Cardiomegaly is often diagnosed by chest X-ray or CT imaging through identifying the cardiothoracic ratio, which measures the ratio of the heart width to the chest width. A ratio of more than 50% indicates cardiomegaly. Treatment of cardiomegaly is based on the underlying conditions, such as hypertension, diabetes and arrhythmias.¹

The relationship between hypertension and cardiomegaly

Hypertension is the medical term used for high blood pressure, and it is associated with various health conditions, including cardiomegaly. Prolonged high blood pressure increases the workload of the heart by forcing the heart to pump against a greater pressure, which may result in structural changes to the heart. To compensate for the demand, the heart may thicken its walls (remodelling) to pump more strongly to maintain adequate blood flow throughout the body, particularly the left ventricle, which supplies oxygenated blood.³

Another complicated system in the human body that regulates fluid retention and blood vessel constriction, the Renin-Angiotensin-Aldosterone system (RAAS), plays a key role in the progression of cardiomegaly.³ This will be discussed in detail later in this article.

Understanding the mechanism of your body, the relationship between the blood pressure and cardiomegaly, and the management of hypertension is therefore important to prevent further heart damage.

Why are antihypertensive drugs recommended for heart enlargement?

Through various mechanisms such as relaxation of the muscles surrounding blood vessels or reduction of water intake and cardiac fibrosis (scarring), these medications decrease blood pressure and the resistance that the heart needs to pump against.  These changes reduce the workload of the heart, preventing progression of cardiomegaly and potentially reversing remodelling. The symptoms of heart enlargement would further improve as the heart function is enhanced.³  

Common antihypertensive drug classes used in heart enlargement

You can think of the human body as a very complicated machine, where various mechanisms and systems are intricately intertwined, working in harmony to sustain life. Disturbance to any of these systems can cause serious outcomes. Through precise interventions guided by knowledge in medical science, these systems can be regulated to treat or manage various conditions. There are various types of antihypertensive drug classes, and not all of them are used in cardiomegaly. If you are dealing with cardiomegaly, your doctor might suggest taking one of these or a combination of these antihypertensive medicines: ACE inhibitors, ARBs, beta-blockers, CCBs, diuretics and aldosterone antagonists.¹

ACE inhibitors (angiotensin-converting enzyme inhibitors)

The renin-angiotensin-aldosterone system plays a vital role in the regulation of blood pressure and the maintenance of heart function. Understanding this system is important to acknowledge how these medicines work, their effects on your body and how they can be helpful for the treatment of cardiomegaly.

Angiotensinogen, mainly produced by the liver, is converted to angiotensin I, an inactive peptide, by renin. Renin is an enzyme released by juxtaglomerular cells of the kidneys. Angiotensin I is then converted to its active form, angiotensin II, by angiotensin-converting enzyme (ACE). Angiotensin II has various actions in our body to regulate blood pressure and maintain homeostasis. Angiotensin II is a potent vasoconstrictor as it narrows the blood vessels, resulting in increased blood pressure. It also stimulates aldosterone release by the adrenal gland, acting on the kidneys to increase reabsorption (retention) of water and salt, further increasing blood pressure. Additionally, angiotensin II promotes cardiac remodelling and scarring (fibrosis), where scar tissue replaces the healthy heart muscle (myocardium).⁴ Myocardium is the muscular layer of the heart composed of cardiac muscle cells, responsible for the pumping action. However, when these healthy cardiac muscle cells are replaced by scar tissue, it thickens. This structural change in the heart reduces the heart's ability to contract, resulting in weaker pumping activity and an increased workload on the heart.⁵

A drug class called angiotensin-converting enzyme inhibitors is considered the first-line treatment of hypertension and can be used in cardiomegaly to prevent further progression. As the name implies, they block the conversion of inactive angiotensin I to angiotensin II. A decrease in angiotensin II levels results in vasodilation and reduced blood pressure, therefore reducing the workload of the heart. Additionally, angiotensin-converting enzyme inhibition decreases aldosterone secretion and heart remodelling, including myocardial hypertrophy (increase in size of the heart), improves heart function over time, and reduces further progression of the condition. Examples of this drug class are Ramipril and Lisinopril.^1,5

ARBs (angiotensin II receptor blockers)

Angiotensin II receptor blockers (ARBs), similarly to ACE inhibitors, act on the renin-angiotensin-aldosterone system (RAAS). This time, instead of blocking the angiotensin II conversion, this drug class directly acts on the angiotensin II receptors and blocks the action. Our cells have various types of receptors, which are protein structures that receive stimuli, triggering cellular responses. If these receptors are blocked, the specific molecule, in this case angiotensin II, can not bind to the receptor to trigger a response. When angiotensin II action is blocked, it promotes blood vessel relaxation and decreased blood pressure, aldosterone secretion and cellular hypertrophy. If a patient cannot tolerate ACE inhibitors due to adverse effects such as coughing, ARBs are recommended as an alternative, as they are generally better tolerated and associated with a lower incidence of adverse effects compared to ACE inhibitors. Examples of drugs included in this class include Losartan and Valsartan.⁵

Aldosterone antagonists (mineralocorticoid receptor antagonists)

Aldosterone antagonists are medications that block the action of aldosterone, a hormone involved in fluid retention and cardiac tissue fibrosis. By reducing aldosterone's effects, they decrease fluid buildup and prevent further fibrosis of heart tissue. These drugs are especially helpful for patients with heart failure and reduced ejection fraction (meaning the heart is less efficient at pumping). An example of this group is Spironolactone.

Beta-blockers

Beta-blockers are medications that inhibit beta receptors predominantly found in the heart, lungs, and kidneys. By blocking these receptors, beta-blockers reduce myocardial contractility, heart rate, and cardiac output, thus lowering the heart's workload. In the kidneys, they also decrease renin release, leading to decreased angiotensin I and II production, which results in vasodilation and reduced cardiac hypertrophy. These actions help improve symptoms and reverse cardiac hypertrophy in patients with heart failure. Carvedilol and Bisoprolol are examples of beta-blockers.

Calcium channel blockers (CCBs)

Calcium channel blockers are drugs that prevent calcium ions from entering cardiac and vascular smooth muscle cells. This reduces the constriction of these muscles, promoting arterial relaxation, lowering peripheral vascular resistance, and reducing blood pressure. In the heart, these drugs decrease the force of contraction (negative inotropic effect) and slow the heart rate (negative chronotropic effect), which together lower cardiac output. Calcium channel blockers are particularly effective in elderly patients or those with isolated systolic hypertension. Amlodipine and Diltiazem are examples of this drug class.

Diuretics

Diuretics reduce salt and water retention, reducing the blood volume and pressure in the veins. This decreases the cardiac workload and remodelling. Diuretics improve symptoms in patients with heart enlargement, such as swelling. Hydrochlorothiazide and Furosemide are the commonly used diuretics.⁵

Combination therapy

A combination of drug classes may be preferred by physicians based on the patient's risk profile and condition to enhance therapeutic efficacy, allowing the medications to work synergistically for improved blood pressure control and reduction of cardiac hypertrophy. Individuals with only mild symptoms benefit from lifestyle modifications and one of the drug classes mentioned, particularly ACE inhibitors, ARBs or beta-blockers. If the patient is experiencing heart failure symptoms, diuretics are added to these medications.¹ ACE inhibitors and beta-blockers can be combined due to their complementary actions, reducing blood pressure and the stress on the heart synergistically.⁷

Treatment should be tailored to individuals, considering other conditions that patients might have, such as diabetes, kidney function and heart failure, as well as the side effects the patients might be experiencing. After the initiation of any drugs, monitoring for the adverse effects and the progress is crucial.

Summary

Cardiomegaly can be the result of various possible underlying conditions. Identifying the primary contributing factor is important for effective treatment and reversal of cardiac hypertrophy. Treatment centres around managing these conditions and reducing their progression. Various classes of hypertensives play key roles in managing heart enlargement.¹ 

ACE inhibitors, aldosterone receptor blockers and aldosterone antagonists act on the renin-angiotensin-aldosterone system and reduce blood pressure, cardiac hypertrophy and remodelling. Beta-blockers inhibit the beta-adrenergic receptor activation, decrease myocardial contractility and cardiac workload. Calcium channel blockers inhibit the influx of calcium, relaxing vascular smooth muscles and producing negative inotropic and chronotropic effects. Diuretics reduce salt and water reabsorption, resulting in decreased blood pressure. Through various mechanisms, all these medications reduce blood pressure and the stress of the heart, improving the symptoms and facilitating the recovery of the heart, potentially reversing cardiomegaly.^1,5  The choice of medication depends on the condition, symptoms and tolerance of the patient. Effective management not only includes drug treatments, but also lifestyle modifications such as maintaining a balanced diet, living smoke-free and staying active.⁸