Introduction

High blood pressure, also referred to as hypertension, is a very common condition affecting more than one billion people worldwide.¹ Hypertension causes changes in the body, particularly the heart, through structural changes in the left atrium (LA). The LA is a small chamber within the heart with thin, muscular walls.² It acts to collect oxygenated blood from the pulmonary veins (a vessel that gathers oxygen-rich blood from the lungs back to the heart) and eventually pushes it up to the aorta and out to the rest of the body.² Studies have shown that long-term hypertension (chronic hypertension) can cause LA enlargement, which translates to an abnormal thickening of the atrial muscles.³ 

Following decades of research, scientists have developed antihypertensive medications to reduce your blood pressure and the likelihood of many heart and stroke-related diseases.  One study has concluded a significant reduction of LA size in cases of mild to moderate hypertension through the use of specific antihypertensive medications.⁴ 

Function of the left atrium

As already stated, the LA is a chamber of the heart with thin muscular walls.² It is located on the posterior and superior aspect of the heart on the left-hand side. The LA works in different ways to aid in the cardiac cycle (the process of how your heart beats and pumps blood). During ventricular ejection, the LA acts to collect the oxygenated blood received from the pulmonary vein. The ventricles then relax in a phase called early diastole. Due to ventricular relaxation and the sudden pressure drop, blood quickly moves from the atria into the ventricles in the phase of passive atrial emptying. Lastly, atrial contraction acts to push one-third of the blood from the atria into the ventricles.² Through the close anatomical relation, clinicians have found that the presence of LA enlargement is often due to increased left ventricular filling pressure and diastolic dysfunction (the ventricle is unable to fill and relax properly).⁵

Hypertension & How does it affect the heart?

Chronic hypertension causes increased pressure within the left ventricle of the heart.⁶ This results in thickening of the muscular walls of the ventricle (left ventricular hypertrophy). The thickened ventricle gradually becomes stiffer and less able to relax and fill with blood.⁶ This blood then backs up into LA, causing increased LA filling pressure. To compensate for the increased pressures, the LA undergoes structural remodelling resulting in hypertrophy and enlargement.² 

Consequently, numerous studies have noted the association between increased LA size and the prognosis of many different heart-related diseases, such as atrial fibrillation (AF) and heart failure (AF is when the atria beat chaotically and irregularly).² The reduced blood pumped to the aorta and around the body can have many different symptoms. 

Symptoms 

Whilst LA enlargement may not directly cause any symptoms, symptoms can arise from the conditions causing the enlargement.⁷ These include:

• Fainting
• Tiredness
• Palpitations 
• Difficulty breathing 
• Lower limb swelling⁷

Understanding Antihypertensive Therapy

The British National Formulary (BNF) identified the objective of antihypertensive medications as reducing cardiac-related mortality, including strokes or myocardial infarctions, commonly known as a heart attack.⁸ These medications help to lower blood pressure and prevent any further damage to the heart and other organs like the kidneys, with each drug class acting in their way. ⁸ Given the wide range of antihypertensive drugs available, clinical judgement and tailored treatment plans are essential before the prescription of any of these drugs. The drug classes are given below.

Angiotensin Converting Enzyme Inhibitor (ACEi) 

ACEi are typically the first-line treatment in people younger than 55 years old and in the presence of someone with chronic kidney disease (CKD).⁹ ACEi’s act by inhibiting the conversion of angiotensin I to angiotensin II in the renin-angiotensin-aldosterone system (RAAS). Angiotensin II acts as a potent vasoconstrictor, causing narrowing of the arteries and increased blood pressure. By preventing its conversion, drugs like ramipril and enalapril cause dilated vessels and reduced blood pressure.⁹

Angiotensin II Receptor Blockers (ARB)

ARBs are a type of antihypertensive drugs that lower your blood pressure by inhibiting the binding of angiotensin II to the angiotensin type I receptor in the RAAS pathway.¹⁰ Similar to the action of ACEi, ARBs, like valsartan and losartan, cause dilation of arteries, lowered blood pressure and reduced aldosterone secretion¹⁰ (a steroid hormone that acts to increase sodium and water absorption and, as a consequence, blood pressure).¹¹

Thiazide & Thiazide-like Diuretics 

Thiazide diuretics like hydrochlorothiazide prevent sodium reabsorption in the distal convoluted tubule of the nephron (a small unit of the kidney's filtration system).¹² By preventing the reabsorption of sodium, water is lost through the kidneys. This lowers the volume of circulating blood and thereby reduces blood pressure.¹²

Calcium Channel Blockers (CCBs)

CCBs, like amlodipine and diltiazem, prevent calcium from moving into the cell by binding to calcium channels located in the heart and vascular smooth muscle¹³ (the muscle found in arteries that control arterial dilation or constriction). This lowers the blood pressure via two different mechanisms. By binding to the calcium channels in the heart, this results in slower myocardial contractility, meaning the heart beats more slowly. The other is through the dilation of peripheral arteries.¹³

How Antihypertensive Therapy Modulates Left Atrial Size

Through the different classes of antihypertensive medication listed, by lowering blood pressure both in the arteries and the heart, the heavy workload on the heart has been reduced. This allows the heart to function more efficiently. 

A study performed by Gottdiener J S et al⁴ found that when patients with mild to moderate hypertension were given hydrochlorothiazide or diltiazem over two years, a significant reduction in LA size was detected when measured with echocardiography. However, whilst hydrochlorothiazide, clonidine, and diltiazem significantly reduced LA size at the one-year mark, hydrochlorothiazide produced a greater decrease in LA size.⁴ Unfortunately, it’s important to remember that clinicians are unable to prescribe hydrochlorothiazide to everyone presenting with LA enlargement. As hydrochlorothiazide is a thiazide diuretic and acts on the kidney, doctors are unable to give this if the person has existing comorbidities like CKD. This is one of the reasons clinical judgement remains paramount in a situation like this. 

A study by Wachtell K et al¹⁴ revealed that when all the key risk factors were looked at together, those with a high LA diameter had a greater risk of developing new-onset AF.  Wachtell K et al also discovered that for every 1 cm increase in LA diameter, you were 5.16 times more likely to develop new-onset AF. On the other hand, for those with a reduced LA diameter, for every 1 cm reduction in LA size, there was a 79% reduction in the risk of AF. Both of these results were statistically significant with a p-value <0.001. This means there is less than a 0.1% chance that these findings are due to random chance.¹⁴ Allowing us to be confident in these results. 

FAQs

What is LA enlargement, and why aren't thicker muscles in the heart a good thing?

In cases of hypertension, the muscles of the LA grow in size and become thicker to compensate for the increased pressure that backs up from the left ventricle.² However, whilst many may think thicker muscles of the heart are a good thing, this stretching causes scarring and injury to the myocardium.⁷ This lowers the LA's ability to stretch and fill with blood. As a result, less blood is pumped to the ventricles and pumped around the body, causing symptoms like fatigue and fainting. 

Is LA enlargement reversible?

Studies like those revealed by Gottdiener J S et al showed evidence of reversed LA size in participants with mild to moderate hypertension.⁴ Whilst these results were promising, they only apply to a certain subset of people with hypertension. There isn't enough evidence to say that these results can be applied to the wider public or how long the reduced LA size will remain after treatment. 

How can I prevent LA enlargement?

As LA enlargement can be a consequence of uncontrolled hypertension, the most manageable lifestyle changes involve:

• Keeping your blood pressure in a normal range (whether that’s through antihypertensive medications or a healthier lifestyle)
• Weight management
• Smoking cessation
• Reduced alcohol intake⁷

It is important to remember that not all cases of LA enlargement are caused by hypertension. That’s why it's important to stay informed, follow up with your doctor regularly and take a proactive role in your health

Summary

Uncontrolled hypertension can cause LA enlargement alongside other heart and stroke-related complications. This results in a structural change of a thicker and stiffer atrium, one less able to relax fully and fill with blood. This reduces the volume of blood pumped out of your heart and causes symptoms of fatigue, tiredness and difficulty breathing. Recent research has found promising new evidence that antihypertensive medications, specifically hydrochlorothiazide, reduce LA size in those with mild to moderate hypertension. This could play an important role in lowering the risk of conditions like new-onset AF and heart failure. 

However, there is insufficient research as to whether the same applies to those with severe hypertension. We can then consider how further research with larger and more varied groups of participants, like those at different stages of hypertension, is needed to decide if this can truly be applied to the general public.