BASIC CARDIAC ELECTROPHYSIOLOGY
Mechanisms of arrhythmia initiation, maintenance, and termination are best understood by reviewing the basic electrophysiologic properties of the cardiac cells. The resting cardiac transmembrane potential is normally –50 to –95 mV (depending on the type of cardiac cell) and is maintained by the electrochemical equilibration of the sodium (Na+), potassium (K+), calcium (Ca2+), and chlorine (Cl–) ions. From an electrophysiological standpoint, cardiac cells can be classified into fast-response (contractile cells) and slow-response (automatic) cells. Sinus node and atrioventricular (AV) node cells are considered slow response cells. The electrophysiological properties during diastole (resting phase) and systole (activation phase) are different.
The cardiac transmembrane action potential of fast response cells consists of 5 phases (Fig. 5-1):
Phase 0: Rapid depolarization is caused by a sudden influx of Na+ ions.
Phase 1 (absent in slow-response cells): Early rapid repolarization due to inactivation of the inward Na+ channels and simultaneous activation of outward K+ channels, resulting in a net efflux of positive ions.
Phase 2 (absent in slow-response cells): The plateau phase may last several hundred milliseconds and is mainly due to the outward K+ and Cl– ion current with an inward current of Na+ and Ca2+.
Phase 3: Final rapid repolarization occurs due to opening of slow delayed rectifier K+ channels and simultaneous closure of inward Na+ and Ca2+ channels, resulting in a net efflux of positive ions.
Phase 4: The resting membrane potential is reached. It is usually rectilinear in fast-response cells due to inward Na+ and Ca2+ currents and outward K+ currents.
In slow-response cells, resting transmembrane potential is slightly less negative (around –60 mV) and is followed by gradual diastolic depolarization, which is responsible for the property of automaticity. Diastolic depolarization is caused predominantly by an inward current of both Na+ and Ca2+ with slow/small outward current of K+.
Different classes of antiarrhythmics have their effects on 1 or more phases (Table 5-1).
|Class||Effect on Phases||Example Drugs|
|Class Ia||Depress phase 0, prolong repolarization||Quinidine, procainamide, disopyramide|
|Class Ib||Depress phase 0, shorten repolarization||Lidocaine, phenytoin, mexiletine|
|Class Ic||Depress phase 0, minimal effect on repolarization||Flecainide, propafenone, moricizine|
|Class II||Decrease slope of phase 4||Propranolol, esmolol, timolol, metoprolol, atenolol|
|Class III||Prolong phase 3||Amiodarone, sotalol, ibutilide, dofetilide|
|Class IV||Prolong phase 2||Verapamil, diltiazem|
|Class V||Adenosine, digoxin, magnesium sulfate|
In addition to class III, amiodarone can act as a class Ia, II, and IV drug.
The conduction system of the heart and their action potentials. (Left panel: Data from Donahue JG, Choo PW, Manson JE, et al. The incidence of herpes zoster. Arch Intern Med. 155:1605-1609, 1995; Choo PW, Galil K, Donahue JG, et al. Risk factors for postherpetic neuralgia. Arch Intern Med. 1997;157:1217-1224. Right panel: Reproduced with permission from Elmoselhi A, Seif M. Electrophysiology of the Heart. In: Elmoselhi A. eds. Cardiology: An Integrated Approach. New York, NY: McGraw-Hill; 2018).
During normal antegrade conduction, an action potential is first generated in the sinoatrial (SA) node due to its automaticity. It is then conducted to the atrioventricular (AV) node, down the bundle of His and into the Purkinje fibers via cell-to-cell conduction facilitated by gap junctions.
The SA node is the natural pacemaker of the heart and is located epicardially, at the junction of superior vena cava and the right atrium. It is heavily innervated by vagal fibers, but also has a high concentration of β-adrenergic receptors, which makes the SA node susceptible to vagal inputs (decreasing automaticity) and circulating catecholamines (increasing automaticity).
The AV node is located within the Koch triangle, anterior to the coronary sinus ostium and just above the septal leaflet of the tricuspid valve. The AV node has pacemaker activity as well but at a slower automaticity than the SA node. Its main function is to cause a delay in the electrical activity between the atria and ventricles in order to coordinate atrial and ventricular contractions. Like the SA node, the AV node is also influenced by vagal inputs and circulating catecholamines.
The bundle of His is located in the membranous portion of interventricular septum and connects the AV node and bundle branches. The bundle of His branches off into right and left bundle branches at the level of the muscular intraventricular septum. The left bundle branch further divides into anterior and posterior fascicles. The ends of these branches then connect with the terminal Purkinje fibers, which form interweaving networks on the endocardial surface of both ventricles.
The normal ECG is made up of a P wave, PR segment, QRS complex, ST segment, T wave, and QT interval. The P wave reflects atrial activation. The PR segment corresponds to the duration of atrioventricular conduction and is normally between 120 and 200 msec. The QRS complex represents the ventricular activation and is normally less than 100 msec. The ST segment and T wave reflect electrical ventricular recovery. The QT interval includes the total duration of ventricular activation and recovery and is normally less than 450 msec. Because the length of the QT interval is heart-rate dependent, a heart-rate adjusted value called QTc (corrected QT) is commonly used.
Tachycardia is defined as heart rate greater than 100 beats per minute (bpm). Sustained tachyarrhythmias are common in critically ill patients and occur at a frequency of approximately 12% in patients admitted to intensive care unit (ICU).1 There are 3 mechanisms of tachyarrhythmias: abnormal automaticity, triggered activity, and reentry.2 Normal automaticity originates in a normal pacemaker site of the heart (eg, sinus tachycardia), whereas abnormal automaticity results from a tissue that, under normal conditions, does not exhibit pacemaker properties but can become automatic under abnormal circumstances (eg, accelerated idioventricular rhythm). Triggered activity refers to spontaneous depolarization that occurs during or immediately after the cardiac action potential, giving rise to extrasystole, which can then precipitate tachyarrhythmias.2 Reentrant tachyarrhythmias result from 2 electrically distinct pathways that connect to create a circuit.
Sinus tachycardia is sinus rhythm at a heart rate greater than 100 bpm and usually reflects an underlying process such as hypovolemia. The management for sinus tachycardia is directed at treating the underlying cause.
Focal atrial tachycardia has a discrete origin within the atrium and will usually generate a regular rhythm ranging from 100 to 250 bpm3 (Fig. 5-2). The P-wave axis on ECG will differ from that of sinus rhythm. Nonsustained focal atrial tachycardias are common and often do not require treatment.
Unlike focal atrial tachycardia, which has a discrete origin, multifocal atrial tachycardia is an irregular rhythm with at least 3 distinct P-wave morphologies on ECG, with a rate between 100 and 130 bpm.3 The mechanism is unclear, but it is associated with underlying conditions, particularly pulmonary disease, pulmonary hypertension, coronary artery disease, and valvular heart disease. First-line management is directed at treating the underlying condition. If needed, AV nodal blockers such as beta-blockers and calcium channel blockers (CCB) can be used to control the heart rate. Neither electrical cardioversion nor oral antiarrhythmics is useful for suppressing this arrhythmia.3
Atrial fibrillation (AF) is the most common sustained arrhythmia4 and occurs when there are structural and/or electrophysiological abnormalities of the atrial tissue5 (Fig. 5-3). It is associated most commonly with structural heart disease, advancing age, hypertension, heart failure, and coronary artery disease.5 Atrial fibrillation can be classified by the duration of episodes. Paroxysmal atrial fibrillation resolves spontaneously or through intervention within 7 days, but episodes may reoccur. Persistent atrial fibrillation may persist for more than 7 days and is considered long-standing persistent AF if it persists for more than 12 months. Permanent atrial fibrillation occurs when attempts to restore to sinus rhythm are stopped. Nonvalvular AF occurs in the absence of rheumatic mitral stenosis, bioprosthetic or mechanical heart valve, or mitral valve repair.5 The ECG will have no discernible P waves and the ventricular rhythm and rate can vary.
Treatment of AF is either to maintain sinus rhythm or to control the heart rate.6 The Pharmacological Intervention in Atrial Fibrillation (PIAF) study showed that there was no difference in symptom improvement from either approach, and a sub-study showed no difference in quality of life.7 The STAF study8 showed no difference with primary endpoints of death, cardiopulmonary resuscitation, cerebrovascular event, and systemic embolism, but more hospitalization in the rhythm-control group from repeated cardioversions and initiation of antiarrhythmic, and a tendency toward greater mortality in the rate-control group (2.5% vs 4.9%). The RACE study9 showed no difference after a 2.3-year follow up for primary endpoints of death from cardiovascular causes, heart failure, thromboembolic complications, bleeding, pacemaker implantation, and adverse drug effects. The AFFIRM study6 followed patients from a mean of 3.5 years to a maximum of 6 years, and 63% of the rhythm-control group were in normal sinus rhythm (NSR) compared to 34.6% of patients in the rate-control group. Despite this, there were 356 deaths (23.8%) in the rhythm-control group versus 310 deaths (21.3%) in the rate-control group, but these rates were not statistically significant.6 Gillinov et al10 showed that rate and rhythm controls were associated with similar days of hospitalization, complication rates, and persistent atrial fibrillation 60 days after onset in patients who develop postoperative atrial fibrillation after cardiac surgery. Rate control can be achieved via beta-blockers, digoxin, diltiazem, or verapamil for a left ventricular ejection fraction (LVEF) of 40% or greater, and beta-blockers or digoxin for LVEF less than 40% (Class of Recommendation [COR] I, Level of Evidence [LOE] B).11 Amiodarone can be given in hemodynamically unstable patients or severely depressed EF (COR IIb, LOE B).11 For rhythm control, flecainide and propafenone can be given if there is no structural heart disease; ibutilide can be given, but there is a risk of torsade de pointes; vernakalant can be given to patients with mild heart failure; and amiodarone can be given to patients with ischemic heart disease and heart failure.11
Thromboembolic risk management is an important part of AF management with the highest risk being advanced age and previous transient ischemic attack (TIA) or cerebrovascular accident (CVA).11 The decision for no anticoagulation versus warfarin versus novel oral anticoagulants (NOAC) is complex and should be based on an individual’s risk of stroke and bleed, which can be determined via CHA2DS2-VASc or CHADS2 scores or the presence of moderate to severe mitral valve stenosis and/or mechanical valves.5 An increase in the stroke risk of approximately 2% with each 1-point increase in CHADS2 score has been shown in multiple non–valvular atrial fibrillation cohorts.12 Compared to the CHADS2 score, the CHA2DS2-VASc score includes a larger number of risk factors. Based on this risk stratification scheme, women cannot achieve a score of 0.5 A CHA2DS2-VASc score of 1 or more for men or 2 or more for women recommends anticoagulation (COR IIa, LOE B), NOAC preferred over vitamin K antagonists (VKA) (COR I, LOE A).11 For moderate to severe mitral valve stenosis or mechanical valves, VKA is preferred for anticoagulation (COR I, LOE A).11 Patients with contraindication to anticoagulation but who are at risk for CVA can opt to have left atrial appendage devices (COR IIb, LOE B).11
For patients who presents with TIA/CVA and new onset atrial fibrillation and after exclusion of hemorrhagic conversion, NOAC is started 1 day after TIA, 3 days after mild CVA (National Institutes of Health Stroke Score [NIHSS] < 8), 6 days after moderate CVA (NIHSS 8–15), and 12 days after severe CVA (NIHSS ≥16) (COR IIa, LOE C).11 Aspirin is initiated until the appropriate time to start NOAC (COR IIa, LOE B). For intracranial hemorrhage, anticoagulants can be initiated 4 to 8 weeks after bleeding is controlled (COR IIb, LOE B).11
Patients who are in atrial fibrillation for more than 48 hours should be on oral anticoagulants for 3 weeks or more prior to cardioversion and continued for 4 weeks or more.
Atrial flutter is a macroreentrant atrial tachycardia that has a constant atrial rate but can have either a constant or a variable ventricular response, depending on the conduction through the AV node (Fig. 5-4). Typical flutter is the result of a reentrant circuit in the right atrium and traverses the cavotricuspid isthmus. It will have the classic “saw-tooth” waves on the ECG at a rate of 250 to 350 bpm. Counterclockwise flutter is characterized by negative flutter waves in the inferior leads with positive P waves in V1; clockwise flutter will show the opposite pattern.3 Atypical flutter is generally due to circuits around scar tissue or surgical incisions, and the cavotricuspid isthmus is not involved.13 It will not have the classic saw-tooth pattern but will have a constant P wave morphology and a rate between 250 to 350 bpm. As with AF, management of atrial flutter is directed at either rate or rhythm control. Rate control is generally less effective in atrial flutter, so rhythm control may be preferred. Radiofrequency ablation is the preferred approach but electrical cardioversion may be utilized. If chemo-cardioversion is preferred, ibutilide is used.14 Additionally, patients with atrial flutter share the same risk of thromboembolism as those with AF; therefore, the same anticoagulation recommendations apply.3
Atrioventricular nodal reentrant tachycardia (AVNRT) is a common, generally benign arrhythmia usually seen in young adults without structural or ischemic heart disease. Syncope is uncommon and sudden cardiac death is very rare3 (Fig. 5-5). It appears to be due to a reentrant circuit within the AV node and perinodal tissues, and utilizes the fast and slow pathways4 and the ventricular rate can range from 110 to 250 bpm.3 “Typical” AVNRT accounts for more than 80% of AVNRT and is initiated by a premature beat, which conducts in an antegrade fashion to the ventricles via the slow pathway and conducts retrogradely to the atria via the fast pathway. This is represented as a negative P waves in the inferior leads and a short RP segment, usually less than 90 ms on the surface ECG.3
AV Nodal Conduction. In AV nodal conduction, there are two pathways, Slow Pathway with short refractory time, and Fast Pathway with long refractory time. In sinus rhythm (A), impulse are conducted through both but reach the bundle of His (H) only through the Fast Pathway. In B, due to the long refractory time of the Fast Pathway, a premature atrial impulse is carried through the Slow Pathway and into the bundle of His. In C and D, the impulse from the Slow Pathway may enter the Fast Pathway retrograde, if it has recovered and reentry. SA = Sinoatrial Node; AV = Atrioventricular Node; H = Bundle of His; RBB = Right Bundle Branch; LBB = Left Bundle Branch.
Atrioventricular reentrant tachycardia (AVRT) is dependent on an accessory pathway in addition to the AV node as part of the reentrant circuit4 (Fig. 5-6). Ventricular rates can vary but are generally between 150 and 250 bpm. Unlike AVNRT, the RP segment in AVRT is usually greater than 90 ms.4 Orthodromic AVRT is the most common type of AVRT. It is usually narrow complex, and the circuit consists of antegrade conduction from the atria to ventricles through the AV node and retrograde conduction from the ventricles to atria over the accessory pathway with completion of the circuit when the atria conduct back into the AV node.3 Preexcited AVRT, including antidromic AVRT, is usually wide complex and uses the accessory pathway for antegrade conduction with retrograde conduction through the AV node. A preexcited QRS complex will have a short PR interval (< 120 ms) and a delta wave (slurred upstroke of the QRS complex). Atrial fibrillation can conduct antegradely via the accessory pathway leading to rapid, irregular, wide, and bizarre-looking QRS complexes.
Accessory pathways. In A, orthodromic AVRT, the impulse is carried through the AV node (AV) and Bundle of His and exits through the Accessory Pathway (AP). This creates a normal QRS. In B, antidromic AVRT, the impulse is carried through the ventricle via the Accessory Pathway and exits via AV node. This creates a wide QRS. AV=Atrioventricular Node; SA=Sinoatrial Node; AP=Accessory Pathway; LBB = Left Bundle Branch; RBB = Right Bundle Branch.
The acute and long term treatment of supraventricular tachyarrhythmias are seen in Figures 5-7 and 5-8).
Acute treatment of supraventricular tachyarrhythmias. AVN = atrioventricular node; AVNRT = atrioventricular nodal reentrant tachycardia; AVRT = atrioventricular reentrant tachycardia; DCCV = direct current cardioversion; IV = intravenous; PO = oral; VFib = ventricular fibrillation; WPW = Wolff-Parkinson-White.
Preexcitation is due to simultaneous antegrade ventricular activation via the AV node and an accessory pathway (Fig. 5-9). The incidence of preexcitation on ECG is about 0.1% to 0.3% of the general population15 with most cases occurring in healthy individuals with no organic heart disease; however, about 7% to 10% of patients have associated Ebstein anomaly.4 When symptoms such as syncope or palpitations accompany preexcitation on ECG, a preexcitation syndrome is established, which has an increased risk of sudden cardiac death of up to 4% over a lifetime.15 Therefore, catheter ablation should be considered for any patient who is at high risk or who has symptoms/tachycardia refractory to medical therapy.4 Medical therapy aimed at slowing conduction through the accessory pathway is reasonable for those patients with high risk but no symptoms.4 In patients with preexcitation and acute tachycardia, it is reasonable to use AV nodal blocking medications if the QRS is narrow. If the QRS is wide, it is unsafe to use AV nodal blocking agents, as this may cause preferential conduction through the accessory pathway leading to ventricular fibrillation. Beta-blockers, CCBs, digoxin, and adenosine are contraindicated. If tachycardia persists, synchronized direct current cardioversion (DCCV) is the treatment of choice.4 Similarly, in those with accessory pathway and another type of supraventricular tachycardia (SVT), such as atrial fibrillation, AV nodal blocking agents should be avoided.15