Introduction

Arrhythmia is a cardiac condition where the heart experiences irregular heartbeats due to a problem with its electrical conduction system. The heart is a vital organ in our body, therefore, it is important to be able to recognise early signs of arrhythmia and seek medical attention as soon as possible. If not treated, arrhythmia can cause damage to the heart, brain and other important organs as well as causing other cardiac conditions like stroke, heart failure and cardiac arrest. These events are life-threatening and may cause death. Cardiovascular diseases are the leading global cause of mortalities; in the US, it is estimated that more than 25% of deaths are caused by cardiac arrhythmias.⁹

There are many drugs that can treat arrhythmia:

• Class I - Sodium channel blockers
• Class II - Beta-blockers
• Class III - Potassium channel blockers 
• Class IV - Calcium channel blockers

Class II beta-blockers play a huge role in arrhythmia treatment. They are often the first line treatment for atrial fibrillation- the most common type of arrhythmia. It is important to understand how beta-blockers work, the potential side effects and to consider all possible treatment options when managing arrhythmia.¹

Understanding causes and symptoms of arrhythmia

Arrhythmia, commonly known as ‘irregular heartbeat’, is a cardiac condition in which there is a problem with the heart’s electrical conduction system, causing the heartbeat to be too fast, too slow or have an irregular rhythm.

Certain risk factors can trigger arrhythmias, however, in some cases the cause is unknown. Genetic mutations can cause inherited arrhythmia. Certain lifestyle habits like smoking, overconsumption of alcohol and the use of illegal drugs can increase the risk of arrhythmia. The chances of arrhythmia also increase with age as older patients are more likely to have other health conditions like high blood pressure, diabetes and thyroid disease as well as taking medications that interfere with blood pressure etc.

The symptoms of arrhythmia include heart palpitations, dizziness, chest pain, shortness of breath, and fatigue.

Types of arrhythmia

There are many different types of arrhythmia, categorised by the speed of heart rate and where they originate in the heart:¹

• Tachycardia - heart rate faster than 100 beats per minute (bpm)
• Bradycardia - heart rate slower than 60 bpm
• Supraventricular arrhythmia - irregular rhythm, typically tachycardias, in the atria (upper heart chambers) or atrioventricular (AV) node which is an electrical conductor

Types of supraventricular arrhythmia include:¹

• Atrial fibrillation - heart beats irregularly or abnormally fast (most common type)
• Atrial flutter - heart experiences regular and rapid heartbeats
• Paroxysmal supraventricular tachycardia (PSVT) - presence of extra electrical pathways between the atria and ventricle, causing an extra heartbeat

Ventricular arrhythmias start in the ventricles (lower heart chambers). This includes:¹

• Ventricular tachycardia - fast, regular and long-lasting beating of the ventricles
• Ventricular fibrillation - rapid and irregular heartbeats cause the ventricles to quiver instead of operating normally. This is a very serious condition as it can lead to cardiac arrest and potentially, death

Ventricular tachycardia increases the risk of ventricular fibrillation.

What are beta-blockers?

The class of drugs most commonly used to treat heart diseases are beta-blockers. As well as cardiac arrhythmias, it is a popular treatment for other cardiac diseases such as tachycardia, hypertension, myocardial infarction and congestive heart failure. Beta-blockers can also be used to treat non-cardiac conditions. This is because there are three different types of beta receptors on which the drug can act on: Beta-1, Beta-2 and Beta-3 receptors. Beta-1 receptors are found in the heart, beta-2 receptors are ubiquitously expressed and mediate control over smooth muscle (e.g. gut) relaxation, and beta-3 receptors induce the breakdown of fat.²

Beta-blockers are antagonists that bind to specific adrenoreceptors and quite literally block the adrenaline and noradrenaline from binding instead. First-generation beta-blockers non-selectively block beta-1 and beta-2 adrenoceptors which can cause side effects when treating cardiovascular diseases. Therefore, most beta-blockers used to treat cardiovascular diseases are second-generation which are more cardioselective for beta-1 (heart) adrenoceptors. Beta-1 adrenoceptors bind to noradrenaline and adrenaline which mediate the pumping and contracting system in the heart. Beta-adrenoceptors are a member of the G-protein coupled receptors (GPCR) family. Beta-blockers compete for binding on these adrenoceptors and block normal ligand binding. This reduces sympathetic tone that mediates myocardial activity. Thus, the therapeutic implications of beta-blockers are their ability to decrease contractility, heart rate and conduction velocity.³

How beta-blockers help in arrhythmia

There are four classes of antiarrhythmic drugs, beta-blockers are class II agents. These drugs work by reducing sympathetic tone on cardiac electrical activity via beta-1 adrenoceptor antagonism. Beta-blockers aid in arrhythmia as they slow sinoatrial and atrioventricular nodal rates (the rate at which electrical signals are conducted in the heart), which stabilises cardiac rhythm and helps the regulation of heart rate. They also reduce proarrhythmic events by preventing sympathetic triggers. Propranolol is a non-selective beta-adrenoceptor antagonist (first generation) used to treat supraventricular and ventricular arrhythmia by stabilising the heart cell membranes. Metoprolol, atenolol and bisoprolol are beta-1 selective antagonists (second generation) that treat arrhythmia by reducing sympathetic activity and stabilising the membrane.⁴

Considerations before taking beta-blockers

As beta-adrenoceptors are ubiquitously expressed, they mediate a range of physiological effects. Beta-blockers are typically well tolerated, however, some may experience adverse effects. The use of non-selective beta-blockers can cause dizziness, nausea, fatigue, diarrhoea, and hyperglycaemia.⁵ Bradycardia and hypotension are potential adverse cardiovascular conditions resulting from the use of beta-blockers. Medical history evaluation is important when considering patient eligibility for beta-blockers. Asthmatic patients may experience bronchospasm when taking non-selective beta-blockers and are therefore advised to opt for beta-1 selective beta-blockers instead.⁶ Patients diagnosed with Raynaud syndrome are advised against taking beta blocks due to the risk of exacerbation.¹ Patients diagnosed with chronic obstructive pulmonary disease are strongly discouraged from taking beta-blockers as they worsen symptoms.

Dosage and administration

Beta-blockers can be administered orally, intravenously, intramuscularly and in ophthalmic form. Dosage and treatment plans depend on the specific drug; long-acting drugs like metoprolol only need to be administered once a day. Most beta-blockers are administered twice daily and some drugs like propranolol are administered 3-4 times a day. Ongoing courses of beta-blockers require constant monitoring and adjustment. Heart rate and blood pressure need to be routinely monitored. Adjustments in dosage or type of beta-blocker may be required if adverse effects arise. It is important to start with a low dose and gradually increase dosage when starting on beta-blockers, as the risk of overdose could lead to lowering heart rate and blood pressure to a dangerous level. 

In cases of beta-blocker overdose, glucagon is administered first, followed by transcutaneous or transvenous pacing if glucagon fails. When ending a course of beta-blockers, it is equally as important to gradually reduce the dosage as opposed to quitting cold turkey. Quitting suddenly can cause rebound angina.^1,7

Combination therapies

Compared to other classes of antiarrhythmic drugs like class I sodium channel blockers and class III potassium channel blockers, beta-blockers have relatively weak antiarrhythmic action. It may be the case that another drug aside from beta-blockers is prescribed to treat arrhythmia. More than one type of antiarrhythmic drug can be used to treat atrial fibrillation/flutter. In cases of beta-blocker contraindication, a potassium or calcium channel blocker may be used instead. Patients may also consider combination therapy to treat arrhythmia. Adopting lifestyle changes can significantly help manage the disorder. Studies have shown that body weight and obesity are strongly associated with the onset of atrial fibrillation; when fat is deposited in the heart, the structural change disrupts the heart’s normal electrical signalling. Maintaining a healthy diet and exercising can help maintain and lose weight, reducing the risk of obesity. Consider quitting or reducing the amount of alcohol, drugs or smoking/cigarettes consumed.⁸

Summary

Beta-blockers are a safe and effective drug used to treat arrhythmia. However, there is much emphasis on individual and personalised medicine. Treatment efficacy can depend on the type of arrhythmia, pre-existing medical conditions, dosage and any displayed side effects. In most cases, patients will undergo combination therapy - both pharmacological and non-pharmacological intervention. Antiarrhythmic drugs display different efficacy depending on the type of arrhythmia, for example, class II sodium channel blockers are the preferred drug class used to treat ventricular tachycardia. Despite this, the use of beta-blockers remains one of the most widely used agents in treating heart rhythm disorders, specifically arrhythmias. Future perspectives and research regarding the management of arrhythmia lie in the technological evolution of cardiac devices and the digitalisation of healthcare, these advancements will aid in the monitoring and management of arrhythmia. Alongside the use of drug treatments like beta-blockers, these combined therapies will improve the quality of life of cardiovascular patients and reduce mortality rates.⁹