When Your Heart Skips a Beat – It Could Be Serious

What is arrhythmia and how can we treat it?

NOTE: This article is also available in another language (FRANÇAIS).

Cardiac arrhythmia is a symptom with many possible causes. An irregular heartbeat could be a sign of coronary artery disease, genetic mutations, electrolyte imbalances, or even blunt force trauma. For example, Buffalo Bills safety Damar Hamlin collapsed on the field after a tackle, which some doctors speculate caused an arrhythmia that led to cardiac arrest.

Every cell in the body requires oxygen, carried by blood that is pumped throughout the body by a beating heart. The heart is a 4 chambered, muscular organ, composed of two atria and two ventricles. It alternately relaxes, allowing chambers to fill with blood and then contracts, forcing blood out of its chambers. Electrical activity, transport of charged ions through cardiac ion channels, is what mediates these important mechanical events. Electrical conduction and the mechanical events are elegantly organized into a precise rhythm because the delivery of oxygenated blood is extremely vital.

We spoke with Charles River experts Brian Roche and James Kramer to learn more about arrhythmias. Brian is a general manager for Pharmacology Discovery Services in Ashland, Ohio, and James is a senior manager for Automated Ion Channel Screening in Cleveland.

Eureka: What exactly is an arrhythmia?

James: An arrhythmia is the irregular beating of the heart that may compromise the pumping action of the heart. There are many types of arrhythmias ranging from those that change the heart rate, making it too slow or too fast. There are others that cause the heart to beat in an irregular manner. The most lethal kind is a ventricular fibrillation which is so chaotic that blood is not pumped efficiently, resulting in oxygen loss to the body and possibly death.

Brian: (During ventricular fibrillation), there are many areas of the left ventricle of the heart that are firing at once. This arrhythmia gives the appearance of the heart as shimmering like a bowl of Jell-O compared to the rhythmic contracting relaxation motion of a normal hearts function.

Eureka: What are the major causes of arrhythmia?

Brian: Most arrhythmias are generated because of cardiovascular disease, metabolic disease, or predisposition from a heart condition. Atherosclerosis (or narrowing of coronary arteries) may lead to insufficient oxygen reaching those cardiac cells downstream of the narrowing or blockage. A myocardial infarction may result from this lack of oxygen as cellular processes are disrupted that may lead to arrhythmia generation. There are also genetic abnormalities that may affect cardiac cellular processes and predispose a person to arrhythmia generation. Other risk factors for arrhythmia generation include hydration status, electrolyte imbalance, body temperature changes, over exertion, previous MI, and age.

James: Some drugs may inadvertently block cardiac ion channels. Seldane, an antihistamine, and Prepulsid, an anti-GERD drug, are two examples of marketed drugs that in rare instances blocked the hERG potassium channel, prolonged the QT interval and caused ventricular fibrillation. It was largely due to rare events like these that made the hERG ion channel assay a requirement.

Eureka: What happened to cause football player Damar Hamlin’s cardiac arrest?

Brian: There is a lot of speculation to the causes of cardiac arrest demonstrated by the NFL athlete Damar Hamlin. As the cardiac arrest appeared to occur just after making a tackle, potentially taking a hit to the chest, he may have suffered from commotio cordis. This is a condition where several factors have to line up: direct force to the heart in an exact location of the chest and within a precise period of the heart’s function. This condition is rare, seen more in younger athletes playing hockey, lacrosse, or baseball where the implement (e.g., puck or ball) hits the young athlete in the chest resulting in ventricular fibrillation and sudden cardiac arrest. There may be other, undiagnosed, heart conditions that could lead to sudden cardiac arrest.

Eureka: How important are automated external defibrillators (AEDs) in offsetting damage from sudden cardiac arrhythmia?

Brian: According to recent statistics, sudden cardiac arrest occurs every 1.7 seconds in America. The automated electrical defibrillator (AED) is an amazing invention that brought this life saving device to areas outside of a hospital and accounts for increasing survival by 80% if initiated with 3 minutes of the cardiac arrest. As survival rates are related to the time the AED is applied, having an AED nearby is critical as it may take 8 to 12 minutes for first responders to arrive at the scene. Every additional minute that passes from the start of cardiac arrest decreases survival rate.

Eureka: What work does Charles River do to research arrythmias, and how drugs could cause them?

James: Our research facility in Cleveland, Ohio, offers the world’s most complete library of validated human ion channel-expressing cell lines. Services range from early functional screens for profiling drug candidates to a complete set of in vitro GLP service products for cardiac risk assessment. We evaluate the effects of new drugs on cardiac ion channels expressed in heterologous cell lines. We have identified many drugs that inadvertently inhibit the function of cardiac ion channels, possibly averting tragic cases of arrhythmias in the clinic.

Brian: The in vivo safety pharmacology groups work closely with the in vitro experts within CRL to assess potential adverse effects of drugs on the cardiovascular system. In particular, the in vivo studies assess the electrocardiogram (ECG) for arrhythmias and/or biomarkers within the ECG intervals of each heartbeat that may indicate the potential for proarrhythmia. We focus on providing the safety profile of the compounds in development, but we are also driven to provide innovation within the field as continued reduction in the risk for the adverse event of proarrhythmia.