Cardiac Arrhythmias: Causes and Manifestations

Cardiac Arrhythmias: Causes and Manifestations

THE Abnormalities in the heart's intrinsic conduction system manifest primarily as cardiac arrhythmias (also called dysrhythmias). These disturbances reflect problems with either 

impulse propagation or impulse initiation.  

Conduction abnormalities are cited as a major cause of arrhythmias.

Disturbances of Impulse Propagation (Conduction Abnormalities)

Conduction disturbances can occur at any point in the conduction pathway and may be partial or complete. They can be caused by factors such as depolarization or abnormal anatomy.

1. Simple Conduction Block: This is a failure of the impulse to propagate through a region of cardiac fibers.

Causes: It can result from disease processes like ischemia or inflammation, or from certain drugs. Injury to tissue (e.g., by stretch or anoxia) can lead to an altered balance of ionic currents, causing depolarization. This depolarization can partially inactivate sodium (INa) and calcium (ICa) channels, slowing the spread of current (conduction) and making the tissue less excitable (partial block) or completely inexcitable (complete block). Metabolism-dependent changes during ischemia and anoxia, such as a fall in intracellular ATP, can activate ATP-sensitive K+ channels (KATP), which tend to keep the membrane potential (Vm) close to the potassium equilibrium potential (EK), making cells less excitable and slowing or blocking conduction. Severe and prolonged reduction of coronary flow, as in myocardial ischemia, can impair the electrical behavior of the heart. Ischemia can lead to a loss of K+ from myocytes and an elevated K+ concentration in the surrounding interstitial fluid, which can cause aberrations of cardiac rhythm and conduction. Under certain pathological conditions, such as when myocardial tissue is deprived of blood supply due to coronary artery disease, fast responses in cardiac muscle may change to slow responses. This conversion can be experimentally induced by blocking fast Na+ channels with tetrodotoxin.

Types of Blocks:

Atrioventricular (AV) Block: This impedes impulse transmission through the AV conduction tissue.

First-degree AV block: Characterized by an abnormal prolongation of the AV conduction time. This is reflected as a prolonged P-R interval on an electrocardiogram (ECG). Most of the prolongation caused by an increased heart rate occurs in the N region of the AV node.

Second-degree AV block: Only a fraction of the atrial impulses are conducted through the AV junction to the ventricles (e.g., a 2:1 conduction pattern). This type of block may serve to protect the ventricles from excessively high contraction frequencies.

Third-degree (complete) AV block: No impulses conduct through the affected area. This means none of the atrial impulses reach the ventricles. For example, complete block at the AV node electrically severs the atria and ventricles, leading to AV dissociation, where each beats under the control of its own pacemakers. The only available ventricular pacemakers are the Purkinje fiber cells, which are unreliable and slow, potentially causing a significant drop in cardiac output and blood pressure18. Strong vagal activity can induce delayed conduction or block, largely in the N region of the AV node. Complete AV block with a slow idioventricular rhythm in the Purkinje network can cause profound bradycardia, often requiring an artificial ventricular pacemaker to maintain adequate cardiac output.

Bundle Branch Block: Impulse conduction may be impaired in the right bundle branch, the main left bundle branch, or divisions of the left bundle branch. This can be a consequence of degenerative processes or coronary artery disease. It leads to characteristic ECG patterns, such as an intermittently wide QRS complex in rate-dependent block within the His-Purkinje system. This block impairs the coordinated spread of the action potential throughout the ventricles, reducing contraction efficiency.

2. Aberrant/Accessory Conduction Pathways: These reflect abnormal anatomy, such as an accessory pathway that rapidly transmits the action potential from the atria to the ventricles, bypassing the normal delay in the AV node7. An example is the bundle of Kent in patients with Wolff-Parkinson-White syndrome, which predisposes affected individuals to supraventricular arrhythmias.

3. Re-entry: This is a type of conduction disturbance where a wave of depolarization travels in a loop and re-enters previously excited tissue. It is a major cause of clinical arrhythmias. Re-entry requires three conditions: a closed conduction loop, a region of unidirectional block (at least briefly), and sufficiently slow conduction around the loop.

4. Unidirectional Block: This is a partial conduction block where impulses travel in one direction but not the opposite. It can result from local depolarization or pathological changes in anatomy. For instance, with an asymmetric lesion, current from many healthy cells might excite a few cells in one direction, but current from the few cannot excite the many in the reverse direction. This allows an impulse to travel down a pathway, encounter a unidirectional block in one branch, travel down an alternative path, and then, if the tissue has recovered, travel retrograde through the blocked region and re-excite the original pathway.

Disturbances of Impulse Initiation (Altered Automaticity)

While the SA node is normally the primary pacemaker, other tissues like the AV node and Purkinje fibers also have intrinsic pacemaker activity. Disturbances in impulse initiation can arise from the SA node itself or from ectopic foci (pacemakers outside the normal centers).

1. Altered Sinoatrial Rhythms: Changes in the SA nodal discharge frequency are usually caused by modulation from the cardiac autonomic nerves.

   1. Sinus Tachycardia: Increased SA node firing rate.

   2. Sinus Bradycardia: Decreased SA node firing rate.

   3. Respiratory Cardiac Dysrhythmia: A normal phenomenon where heart rate subtly changes with each respiratory cycle, reflecting modulation of the SA node by cyclic variations in autonomic tone. Loss of this variation can indicate autonomic dysfunction.

   4. Overdrive Suppression: If an ectopic focus suddenly fires at a high rate, the SA node may remain quiescent for a brief period after the ectopic activity stops. A markedly prolonged sinus node recovery time can occur in patients with sick sinus syndrome37..., potentially leading to a period of cardiac standstill (asystole) and loss of consciousness.

2. Activity from Ectopic Foci: Ectopic pacemakers can serve as safety mechanisms if the normal pacemaking centers fail. However, if an ectopic center fires while the normal SA node is still active, it can induce rhythm disturbances.

   1. Premature Depolarizations (Extrasystoles): These are sporadic rhythm disturbances. An extrasystole is an extra contraction that occurs when a stimulus falls during diastole, followed by a compensatory pause.

   2. Abnormal Automaticity: Under certain conditions, even cells that do not normally have pacemaker properties, like ventricular muscle, can develop abnormal automaticity. For example, a prolonged action potential can lead to an early afterdepolarization. If this afterdepolarization reaches threshold, it can trigger a sequence of slow, pacemaker-like action potentials.

Resulting Arrhythmias

These abnormalities in conduction and automaticity can lead to various types of arrhythmias, including:

Premature depolarizations

Tachycardias: Excessively fast heart rates. This includes supraventricular tachycardia. (which can occur paroxysmally) and ventricular tachycardias. (defined as three or more ventricular extrasystoles). Ventricular tachycardia is life-threatening as it can degenerate into ventricular fibrillation.

Bradycardias: Excessively slow heart rates.

Fibrillation: Rapid, irregular, uncoordinated twitchings of muscle fibers that pump no blood43.... Atrial fibrillation, and ventricular fibrillation exist. Ventricular fibrillation leads to loss of consciousness within seconds and no meaningful cardiac output.

Genetic Basis of Some Arrhythmias

Mutations in genes encoding cardiac ion channels are linked to some inherited forms of cardiac arrhythmias, such as Long QT syndrome (LQTS). LQTS can be detected by a prolonged QT interval on an ECG. Mutations in genes like KCNQ1, KCNH2, and SCN5A alter the function of potassium or sodium channel proteins, leading to conditions like LQT1 or LQT3 syndromes. Acquired LQTS is also common and is often due to drug blockade of hERG potassium channels