What is cardiac arrhythmia?

Cardiac arrhythmia is an irregular heartbeat. Irregular in the sense the heart can beat too fast (tachycardia), too slow (bradycardia) or have an abnormal rhythm. There is a wide variety of cardiac arrhythmia and some are harmless while others could be life-threatening. Arrhythmias are concerning because they can potentially reduce the amount of blood being pumped through the body. Because blood carries oxygen to all the tissues in the body, a reduction in blood flow could lead to organ damage.

How is the heartbeat generated?

The heart consists of 4 chambers: two upper chambers called the atria and two lower chambers called the ventricles. A heartbeat is initiated by an electrical signal generated in a group of cells at the top of the right atrium called the sinus node or sinoatrial (SA) node. The signal travels down through the atria which causes them to contract and pump blood into the ventricles. The signal moves down to a second node between the atria and ventricles called the atrioventricular (AV) node. Once the ventricles are full of blood, the signal travels down the ventricles on a pathway called the bundle of His. This causes the ventricles to contract and pump blood to the lungs or other areas of the body. The ventricles then relax and the process starts over again. In a healthy heart 60 to 100 signals are sent per minute. Any issues that arise in this process could lead to cardiac arrhythmia.

What causes cardiac arrhythmia?

Heart arrhythmia is caused by anything that blocks, delays, or alters the electrical signals that regulate the heartbeat. Changes to these electrical signals can be due to a number of reasons including:

•       Damage to the AV or SA nodes
•       Damage to the bundle of His
•       Production of electrical signals in other parts of the heart

Other causes of arrhythmia include:

Smoking or High Levels of Nicotine

The mechanism by which smoking induces cardiac arrhythmia is not known. However, there are some hypotheses. Evidence from clinical studies suggests that nicotine can cause atrial fibrillation. Smoking also promotes coronary heart disease and chronic obstructive pulmonary disease (COPD) which themselves can promote arrhythmias.  Many clinical trials have also found that smokers have an increased risk of developing cardiac arrhythmia conditions compared to non-smokers.

Nicotine

Nicotine has been linked to several forms of cardiac arrhythmia including:

•       Transient sinus arrest
•       Bradycardia
•       Sinus tachycardia
•       Atrial fibrillation
•       Sinoatrial block
•       AV block
•       Ventricular tachyarrhythmia

Nicotine promotes irregular heartbeat through many pathways. For example, nicotine can increase the levels of catecholamine (a type of neuromodulator and hormone) in the blood. High catecholamine levels can increase heart rate, and blood pressure, while extremely high levels can cause arrhythmia.  Nictoine can also directly bind to and block a potassium channel called (I K1), which can also result in irregular heartbeat. This block specifically occurs when nicotinic acetylcholine receptors (nAChR) are not stimulated and catecholamines are released. This is in line with studies that find that low levels of the I K1 receptor is associated with the generation of arrhythmias.

An animal study in which dogs were exposed to nicotine (a level equal to smoking two cigarettes in a human) found that it induced several different types of arrhythmia. The most common were supraventricular arrhythmias such as supraventricular bradycardia, supraventricular arrhythmia, sinus arrest, atrial ectopics and atrial tachycardia. These animals also experienced atrioventricular junctional arrhythmias (escape beats, premature contractions, first-degree heart block, second degree heart block and atrioventricular dissociation) and ventricular arrhythmias (ventricular premature contractions and sustained ventricular tachycardia). Even higher doses resulted in fatal irregular heart beat resulting from ventricular flutter and ventricular fibrillation.

Nicotine has also been found to increase atrial fibrosis (thickening of the atria), particularly after heart failure, which in turn increases the likely hood of atrial fibrillation. Nicotine is through to cause atrial fibrosis by blocking the activity of two micro-RNA (mi-R-133 and miR-590) which inhibit transforming growth factor (TGF)-β1 and TGF-β receptor type II —modulators of connective tissue growth factor.

Not only is nicotine from smoking potentially harmful, but chewing nicotine and inhaling nicotine not in cigarettes can increase the chances of developing short-term atrial fibrillation.

Carbon Monoxide

Nicotine is not the only component of tobacco smoke that promotes heart arrhythmia. Carbon monoxide has also been shown to be harmful. Carbon monoxide inhaled in cigarette smoke binds to hemoglobin, the protein in red blood cells that transports oxygen, resulting in fewer cells that are available to carry oxygen, and fewer cells that are capable of releasing oxygen.  Carbon monoxide increases susceptibility to ventricular fibrillation and ventricular arrhythmia in dogs with ventricular tachycardia.

Oxidative Stress

There is conflicting clinical trial evidence suggesting that oxidative stress induced from smoking may also contribute to atrial fibrillation. However, animal studies have shown that oxidative stress can alter heart tissue resulting in more arrhythmogenic events. There is evidence that smoking-related oxidative stress promote various cardiovascular diseases.

Environmental Tobacco Smoke

Some studies have found an association between heart rate variability and environmental tobacco smoke exposure.

Postoperative atrial fibrillation associated with smoking

Up to 30% of patients experience postoperative atrial fibrillation (POAF) following heart surgery. There is evidence that smoking may actually reduce the risk of developing POAF.  This is believed to be because smoking results in a higher adrenergic state, which allows smokers to tolerate increases in catecholamine induced from surgical stress. This protective effect disappears in people that have quit smoking.

Heavy alcohol use

Drinking alcohol can slow the intra-atrial conduction, the His-ventricular interval and shortened sinus node recovery time during electrical impulse stimulation of the heartbeat. Atrial and ventricular tachyarrhythmia could be induced in 71% of cases in moderate to heavy drinkers. Patients with atrial fibrillation that drink experience shorter atrial refractory times and slowed conduction compared to nondrinkers.

There are several potential mechanisms by which alcohol could promote cardiac arrhythmia. Alcohol has been shown to cause damage to gap junction intracellular channels resulting in abnormal signal conduction. It can cause myocyte (heart cell) damage and inflammation as well as short term oxidative stress. Not surprisingly, alcohol has several electrophysiological effects such as reducing atrial and pulmonary vein action potentials, shortening the atrial refractory period. Reducing the speed of intra- and inter-atrial conduction and enhancing AV-node conduction.  Lastly, alcohol can have autonomic effects on the heart such as shorten the activity of the vagal nerve, the nerve that stimulates the pulse that causes the heart to beat, reducing heart rate variability and inhibiting vagal nerve activity.

Long term consumption of alcohol leads to several conditions that can case changes to atrial activity leading to AF. These conditions include left ventricle remodeling, obstructive sleep apnea, high blood pressure, atrial inflammation and oxidative stress. These conditions promote left atrial remodeling, dilation, fibrosis and increase left atrial pressure. These factors, supported by vagal nerve activation and short term bind drinking promote atrial fibrillation.

Substance Abuse (specifically cocaine and amphetamines)

•       Some prescription and over-the-counter drugs

High levels of caffeine

Animal studies revealed that treatment with caffeine reduced susceptibility to ventricular fibrillation in non-ischemic and ischemic animal models. However, this increase in susceptibility can block by treatment with beta blockade. Animals taking high doses, but not moderate doses, also were more susceptible to ventricular tachycardia induced by ventricular pacing. Another study observed an increase in the incidence of supraventricular and ventricular arrhythmias, while other forms of arrhythmia (ventricular tachycardia, atrial flutter and atrial fibrillation) were seen at higher doses. Caffeine is also capable of increasing the rate of spontaneous discharge from active fibers.

Human studies have found that caffeine can affect the refractory period of atrial, ventricular and nodal tissue. However, it is unclear how this relates to susceptibility for arrhythmia. Patients with ventricular ectopy have an increased risk of experiencing heart beat irregularities when ingesting caffeine. However, there is insufficient evidence to show an increase in risk for other patients already susceptible to cardiac arrhythmia such as patients that have recently experienced a heart attack, non-sustained ventricular tachycardia, or malignant ventricular arrhythmia.

•       Emotional distress such as  intense emotional stress and anger

o   Emotional distress causes the heart to pump harder, resulting in raised blood pressure and release of stress hormones that can cause arrhythmias

•       Heart Failure

Heart failure occurs when the body is unable to pump body in a way that sufficient supplies the body with blood. Atrial fibrillation occurs in 19-37% of individuals living with heart failure. However, it occurs in up to 50% of individuals hospitalized during heart failure.

•       Heart conditions that damage the heart’s electrical system such as:

o   High blood pressure

o   Coronary heart disease

o   Heart failure

o   Overactive thyroid gland (high thyroid hormone production)

o   Underactive thyroid gland (low thyroid hormone production)

o   Rheumatic heart disease

•       Congenital heart defects (i.e. heart effects present at birth) like Wolff-Parkinson-White syndrome.