Emergent Management of Asystole

Background

Asystole is cardiac standstill with no cardiac output and no ventricular depolarization, as shown in the image below; it eventually occurs in all dying patients.

Rhythm strip showing asystole.

Pulseless electrical activity (PEA) is the term applied to a heterogeneous group of dysrhythmias unaccompanied by a detectable pulse. Bradyasystolic rhythms are slow rhythms; they can have a wide or narrow complex, with or without a pulse, and are often interspersed with periods of asystole. When discussing pulseless electrical activity, ventricular fibrillation (VF) (see the following image) and ventricular tachycardia (VT) are excluded.

Rhythm strip showing ventricular fibrillation. NextPathophysiology

Asystole can be primary or secondary. Primary asystole occurs when the heart's electrical system intrinsically fails to generate a ventricular depolarization. This may result from ischemia or from degeneration (ie, sclerosis) of the sinoatrial (SA) node or atrioventricular (AV) conducting system. Primary asystole is usually preceded by a bradydysrhythmia due to sinus node block-arrest, complete heart block, or both.

Reflex bradyasystole/asystole can result from ocular surgery,[1, 2] retrobulbar block, eye trauma, direct pressure on the globe, maxillofacial surgery, hypersensitive carotid sinus syndrome, or glossopharyngeal neuralgia. Episodes of asystole and bradycardia have been documented as manifestations of left temporal lobe complex partial seizures.[3] These patients experienced either dizziness or syncope. No sudden deaths were reported, but the possibility exists if asystole were to persist. The longest interval was 26 seconds.

Secondary asystole occurs when factors outside of the heart's electrical conduction system result in a failure to generate any electrical depolarization. In this case, the final common pathway is usually severe tissue hypoxia with metabolic acidosis. Asystole or bradyasystole follows untreated ventricular fibrillation and commonly occurs after unsuccessful attempts at defibrillation. This forebodes a dismal outcome.

PreviousNextEtiology

Causes of primary and secondary asystole are briefly reviewed in this section.

Primary asystole

Primary asystole develops when cellular metabolic functions are no longer intact and an electrical impulse cannot be generated. With severe ischemia, pacemaker cells cannot transport the ions necessary to affect the transmembrane action potential. Implantable pacemaker failure may also be a cause of primary asystole.

Proximal occlusion of the right coronary artery can cause ischemia or infarction of both the sinoatrial (SA) and the atrioventricular (AV) nodes. Extensive infarction can cause bilateral bundle-branch block (ie, infranodal complete heart block).

Idiopathic degeneration of the SA or AV node can result in sinus arrest-block and/or AV heart block, respectively. This process is slow and progressive, but the symptoms may be acute and asystole may result. An implantable pacemaker is usually required for these conditions.

Occasionally, asystolic sudden death occurs from congenital heart block, local tumor, or cardiac trauma.[4]

Asystole can occur following an indirect lightning strike (ie, direct current [DC]) that depolarizes all the cardiac pacemakers. A rhythm may return spontaneously or shortly after cardiopulmonary resuscitation (CPR) is initiated. These patients may survive intact if given immediate attention. Alternating current (AC) from man-made sources of electrical current usually results in ventricular fibrillation (VF).

Secondary asystole

Examples of common conditions that can result in secondary asystole include suffocation, near drowning, stroke, massive pulmonary embolus, hyperkalemia, hypothermia, myocardial infarction (MI) complicated by VF or ventricular tachycardia (VT) that deteriorates to asystole, post defibrillation, and sedative-hypnotic or narcotic overdoses leading to respiratory failure.

Hypothermia is a special circumstance, because asystole can be tolerated for a longer period under such conditions and can be reversed with rapid rewarming while CPR is being performed. If available, institute cardiopulmonary bypass immediately, because it can accomplish both of these goals. Most survivors have received cardiopulmonary bypass.

PreviousNextEpidemiology

The number of US adults in cardiopulmonary arrest who had bradyasystole as the initial arrest rhythm is difficult to measure accurately. Reports vary and may be skewed by the patient population studied and/or by the method of reporting the initial rhythm. For example, in a 1991 study of 185 patients in cardiopulmonary arrest at the time of arrival to the emergency department, 9% had survived to hospital admission but none were discharged alive.[5] This study was not limited to patients with asystole.[5] In one study from Goteborg, Sweden, asystole was the presenting rhythm in the field in 35% of patients with cardiac arrest.[6]

Race is not a significant factor in asystole except as it relates to the underlying conditions that may lead to a cardiac arrest, such as chronic hypertension, renal failure, coronary artery disease, congestive heart failure, or cardiac dysrhythmias.

Individuals with low CAD incidence

When the incidence of coronary artery disease (CAD) in the population of a country is relatively low, asystole is relatively more common as a manifestation of cardiopulmonary arrests. This is because cardiac ischemia more frequently results in ventricular fibrillation (VF).

Children

The prevalence of asystole as the presenting cardiac rhythm is lower in adults (25-56%) than in children (90-95%). In fact, asystole is most likely to be found in cardiopulmonary arrests occurring in children; this is usually secondary to another noncardiac event (ie, respiratory arrest due to sudden infant death syndrome [SIDS], infection, choking, drowning, or poisoning).[7] Infants are more statistically likely to suffer a cardiac arrest than older children or adolescents.

The Resuscitation Outcomes Consortium Epistry-Cardiac Arrest trial, nontraumatic cardiac arrest occurred at a rate of 72.1 per 100,000 infants versus 3.73 per 100,000 in children and 7.37 per 100,000 in adolescents.[8] Investigators found the adult rate of cardiac arrest was 126.52 per 100,000 when they evaluated 25,405 adults and 624 patients younger than 20 years.

Pediatric patients with VF or ventricular tachycardia (VT) were 4 times more likely to survive an out-of-hospital cardiac arrest (20%) than those with asystole (5%), and patients younger than 20 years had an overall better survival rate than adults when all rhythms are included and traumatic arrests are excluded.[8]

Women

The frequency of asystole, as a percentage of all cardiopulmonary arrests, is higher in women than in men; however, the frequency of cardiac arrest in general is proportional to the underlying incidence of heart disease, which is more common in males until around age 75 years.

PreviousNextPrognosis

The prognosis in asystole depends on the etiology of the asystolic rhythm, timing of interventions, and success or failure of advanced cardiac life support (ACLS).

Resuscitation is likely to be successful only if it is secondary to an event that can be corrected immediately, such as a cardiac arrest due to choking on food (a cafe coronary), and only if an airway can be established and the patient may be rapidly reoxygenated. Occasionally, primary asystole can be reversed if it is due to pacemaker failure, which could be either intrinsic or extrinsic, and this is corrected immediately by external pacing.

Generally, the prognosis is dismal regardless of its initial cause; in particular, individuals with postcountershock asystole have an even worse survival rate.[9, 10] In the Termination of Resuscitation study, when no shock was advised in patients with unwitnessed cardiac arrest, there were no survivors.[11, 12] In the Goteborg, Sweden, study, 10% of 1,635 asystolic patients survived to hospital admission, but 2% survived to hospital discharge.[6]

The most recent American Heart Association guidelines to improve cardiocerebral resuscitation (CCR) have validated studies that show improved outcomes in all adults with out-of-hospital cardiac arrest in ventricular tachycardia and ventricular fibrillation only.[13]

Complications

Complications from asystole include permanent neurologic impairment and complications from cardiopulmonary resuscitation (CPR) or invasive procedures (eg, liver laceration, fractured ribs, pneumothorax, hemothorax, air embolus, aspiration, gastric/esophageal rupture). Death often occurs.

PreviousNextPatient Education

Advice about electrical storm safety and prevention of hypothermia is appropriate for those likely to be exposed to these conditions.

For patient education information, see Heart Health Center as well as Cardiopulmonary Resuscitation (CPR), Heart Attack, and Coronary Artery Disease.

PreviousProceed to Clinical Presentation , Emergent Management of Asystole

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First-Degree Atrioventricular Block

Background

First-degree atrioventricular (AV) block, or first-degree heart block, is defined as prolongation of the PR interval on an electrocardiogram (ECG) to more than 200 msec.[1] The PR interval of the surface ECG is measured from the onset of atrial depolarization (P wave) to the beginning of ventricular depolarization (QRS complex). Normally, this interval should be between 120 and 200 msec in the adult population. First-degree AV block is considered “marked” when the PR interval exceeds 300 msec.[2]

Whereas conduction is slowed, there are no missed beats. In first-degree AV block, every atrial impulse is transmitted to the ventricles, resulting in a regular ventricular rate.

NextPathophysiology

The atrioventricular node (AVN) is the only normal electrical connection between the atria and the ventricles. It is an oval or elliptical structure, measuring 7-8 mm in its longest (anteroposterior) axis, 3 mm in its vertical axis, and 1 mm transversely. The AVN is located beneath the right atrial endocardium, dorsal to the septal leaflet of the tricuspid valve, and about 1 cm superior to the orifice of the coronary sinus.

The bundle of His originates from the anteroinferior pole of the AVN and travels through the central fibrous body to reach the dorsal edge of the membranous septum. It then divides into right and left bundle branches. The right bundle continues first intramyocardially, then subendocardially, toward the right ventricular apex. The left bundle continues distally along the membranous septum and then divides into anterior and posterior fascicles.

Blood supply to the AVN is provided by the AVN artery, a branch of the right coronary artery in 90% of individuals and of the left circumflex coronary artery in the remaining 10%. The His bundle has a dual blood supply from branches of anterior and posterior descending coronary arteries. Likewise, the bundle branches are supplied by both left and right coronary arteries.

The AVN has a rich autonomic innervation and is supplied by both sympathetic and parasympathetic nerve fibers. This autonomic innervation has a major role in the time required for the impulse to pass through the AVN.

The PR interval represents the time needed for an electrical impulse from the sinoatrial (SA) node to conduct through the atria, the AVN, the bundle of His, the bundle branches, and the Purkinje fibers. Thus, as shown in electrophysiologic studies, PR interval prolongation (ie, first-degree AV block) may be due to conduction delay within the right atrium, the AVN, the His-Purkinje system, or a combination of these.

Overall, dysfunction at the AVN is much more common than dysfunction at the His-Purkinje system. If the QRS complex is of normal width and morphology on the ECG, then the conduction delay is almost always at the level of the AVN. If, however, the QRS demonstrates a bundle-branch morphology, then the level of the conduction delay is often localized to the His-Purkinje system.

Occasionally, the conduction delay can be the result of an intra-atrial conduction defect. Some causes of atrial disease resulting in a prolonged PR interval include endocardial cushion defects and Ebstein anomaly.[3]

PreviousNextEtiology

The following are the most common causes of first-degree AV block:

Intrinsic AVN diseaseEnhanced vagal toneAcute myocardial infarction (MI), particularly acute inferior wall MIMyocarditisElectrolyte disturbances (eg, hypokalemia, hypomagnesemia)Drugs (especially those drugs that increase the refractory time of the AVN, thereby slowing conduction)

A number of specific disorders and events have been implicated (see below).

Athletic training

Well-trained athletes can demonstrate first-degree (and occasionally higher degree) AV block owing to an increase in vagal tone.

Coronary artery disease

Coronary artery disease is a factor. First-degree AV block occurs in fewer than 15% of patients with acute MI admitted to coronary care units. His bundle electrocardiographic studies have shown that, in most of these patients, the AVN is the site of conduction block.

AV block is more common in the setting of inferior MI. In the Thrombolysis in Myocardial Infarction (TIMI) II study, high-degree (second- or third-degree) AV block occurred in 6.3% of patients at the time of presentation and in 5.7% in the first 24 hours after thrombolytic therapy.[4]

Patients with AV block at the time of presentation had a higher in-hospital mortality than patients without AV block; however, the 2 groups had similar mortalities during the following year.[4] Patients who developed AV block after thrombolytic therapy had higher mortalities both in hospital and during the following year than patients without AV block. The right coronary artery was more often the site of infarction in patients with heart block than in those without heart block.

Patients with AV block are believed to have larger infarct size. However, the prevalence of multivessel disease is not higher in patients with AV block.

Idiopathic degenerative diseases of conduction system

Lev disease is due to progressive degenerative fibrosis and calcification of the neighboring cardiac structures, or “sclerosis of the left side of cardiac skeleton” (including the mitral annulus, central fibrous body, membranous septum, base of the aorta, and crest of the ventricular septum). Lev disease has an onset about the fourth decade and is believed to be secondary to wear and tear on these structures caused by the pull of the left ventricular musculature. It affects the proximal bundle branches and is manifested by bradycardia and varying degrees of AV block.

Lenègre disease is an idiopathic, fibrotic degenerative disease restricted to the His-Purkinje system. It is caused by fibrocalcareous changes in the mitral annulus, membranous septum, aortic valve, and crest of the ventricular septum. These degenerative and sclerotic changes are not attributed to inflammatory or ischemic involvement of adjacent myocardium. Lenègre disease involves the middle and distal portions of both bundle branches and affects a younger population than Lev disease does.

Drugs

Drugs that most commonly cause first-degree AV block include the following:

Class Ia antiarrhythmics (eg, quinidine, procainamide, disopyramide)Class Ic antiarrhythmics (eg, flecainide, encainide, propafenone)Class II antiarrhythmics (beta-blockers)Class III antiarrhythmics (eg, amiodarone, sotalol, dofetilide, ibutilide)Class IV antiarrhythmics (calcium channel blockers)Digoxin or other cardiac glycosidesMagnesium

Although first-degree AV block is not an absolute contraindication for administration of drugs such as calcium channel blockers, beta-blockers, digoxin, and amiodarone, extreme caution should be exercised in the use of these medications in patients with first-degree AV block. Exposure to these drugs increases the risk of developing higher-degree AV block.

Mitral or aortic valve annulus calcification

The main penetrating bundle of His is located near the base of the anterior leaflet of the mitral valve and the noncoronary cusp of the aortic valve. Heavy calcium deposits in patients with aortic or mitral annular calcification is associated with increased risk of AV block.

Infectious disease

Infective endocarditis, diphtheria, rheumatic fever, Chagas disease, Lyme disease, and tuberculosis all may be associated with first-degree AV block. Extension of the infection to the adjacent myocardium in native or prosthetic valve infective endocarditis (ie, ring abscess) can cause AV block. Acute myocarditis caused by diphtheria, rheumatic fever, or Chagas disease can result in AV block.

Collagen vascular disease

Rheumatoid arthritis, systemic lupus erythematosus (SLE), and scleroderma all may be associated with first-degree AV block. Rheumatoid nodules may occur in the central fibrous body and result in AV block. Fibrosis of the AVN or the adjacent myocardium in patients with SLE or scleroderma can cause first-degree AV block.

Doppler echocardiographic signs of first-degree AV block have been demonstrated in about 33% of fetuses of pregnant women who are anti-SSA/Ro 52-kd positive.[5] In most of these fetuses, the blocks resolved spontaneously. However, progression to a more severe degree of block was seen in 2 of the fetuses. Serial Doppler echocardiographic measurement of AV-time intervals can be used for surveillance of these high-risk pregnancies.

Iatrogenesis

First-degree AV block occurs in about 10% of patients who undergo adenosine stress testing and is usually hemodynamically insignificant. Patients with baseline first-degree AV block more often develop higher degrees of AV block during adenosine stress testing. These episodes, however, are generally well tolerated and do not require specific treatment or discontinuance of the adenosine infusion.[6]

Marked first-degree AV block may occur after catheter ablation of the fast AVN pathway with resultant conduction of the impulse via the slow pathway. This may result in symptoms similar to those of the pacemaker syndrome.

First-degree AV block (reversible or permanent) has been reported in about 2% of patients who undergo closure of an atrial septal defect using the Amplatzer septal occluder.[7] First-degree AV block can occur following cardiac surgery. Transient first-degree AV block may result from right heart catheterization.

PreviousNextEpidemiology

In the United States, the prevalence of first-degree AV block among young adults ranges from 0.65% to 1.6%. Higher prevalence (8.7%) is reported in studies of trained athletes. The prevalence of first-degree AV block increases with advancing age; first-degree AV block is reported in 5% of men older than 60 years.[8] The overall prevalence is 1.13 cases per 1000 lives.

In a study of 2,123 patients aged 20-99 years, first-degree AV block was more prevalent among African-American patients than among Caucasian patients in all age groups except for those in the 8th decade of life.[8] In this study, the prevalence of first-degree AV block increased at age 50 years in both ethnic groups and gradually increased with advancing age. The peak in African-American patients occurred in the 10th decade of life, whereas the peak in Caucasian patients was in the 9th decade of life.[8]

PreviousNextPrognosis

The prognosis for isolated first-degree AV block is very good. This condition carries no increased risk of mortality, and progression from isolated first-degree heart block to high-degree block is very uncommon.[9] Patients with first-degree AV block and infranodal blocks, however, are at increased risk for progression to complete AV block.

Heart block in children with Lyme carditis tends to resolve spontaneously, with median recovery in 3 days (range, 1-7 days).[10]

Cheng et al found that first-degree heart block is associated with increased long-term risks of atrial fibrillation, pacemaker implantation, and all-cause mortality.[11] Their community-based cohort included 7575 individuals from the Framingham Heart Study who underwent baseline routine 12-lead ECG in 1968-1974 and were followed prospectively through 2007.

Compared with individuals whose PR intervals were 200 msec or shorter, those with first-degree AV block had a 2-fold adjusted risk of atrial fibrillation, a 3-fold adjusted risk of pacemaker implantation, and a 1.4-fold adjusted risk of all-cause mortality.[11] Each 20-msec increment in PR interval was associated with an adjusted hazard ratio (HR) of 1.11 for atrial fibrillation, 1.22 for pacemaker implantation, and 1.08 for all-cause mortality.

Although no significant mortality or morbidity is related to isolated first-degree AV block, first-degree AV block in the setting of acute inferior MI may herald higher degrees of AV block. Markedly prolonged PR interval in patients with left ventricular systolic dysfunction may impair ventricular filling and thus reduce cardiac output.

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Multifocal Atrial Tachycardia

Overview of Multifocal Atrial Tachycardia

Multifocal atrial tachycardia (MAT) is a cardiac arrhythmia caused by multiple sites of competing atrial activity. It is characterized by an irregular atrial rate greater than 100 beats per minute (bpm). Atrial activity is well organized, with at least 3 morphologically distinct P waves, irregular P-P intervals, and an isoelectric baseline between the P waves.

Shine, Kastor and Yurchak first proposed this definition of MAT in 1968.[1] MAT has previously been described by terms such as chaotic atrial rhythm or tachycardia, chaotic atrial mechanism, and repetitive paroxysmal MAT.

Usually, treatment of the patient's underlying problem (eg, respiratory failure, sepsis, theophylline toxicity) takes therapeutic precedent. The condition is transient and resolves when the underlying condition improves.

For more information, see Atrial Tachycardia

NextPathophysiology of MAT

The mechanism of the arrhythmia has not been well defined. Delayed afterdepolarizations leading to triggered automaticity are postulated to result in the development of multifocal atrial tachycardia (MAT). The evidence that implicates this mechanism is mainly indirect and points to intracellular calcium overload by various mechanisms (eg, catecholamine excess, phosphodiesterase inhibition, acidosis, hypoxemia). Electrolyte imbalances associated with severe underlying illnesses can further potentiate the development of this arrhythmia. MAT most often is found in the elderly patient with decompensated chronic lung disease and should be thought of as a hypoxic complication of underlying heart conduction pathology. However, other underlying causes may be present, such as heart failure, sepsis, or methylxanthine toxicity. The effect of MAT on the heart’s conduction system may or may not lead to hemodynamic instability.

PreviousNextEtiology of MAT

Causes of multifocal atrial tachycardia (MAT) are mainly related to underlying illnesses. The following common underlying illnesses are associated with this arrhythmia:

Decompensated chronic lung diseaseCoronary artery diseaseHeart failureValvular heart diseaseDiabetes mellitusHypokalemiaHypomagnesemiaAzotemiaPostoperative statePulmonary embolism PneumoniaSepsisMethylxanthine toxicityPreviousNextEpidemiology of MAT

Multifocal atrial tachycardia (MAT) is a relatively infrequent arrhythmia, with a prevalence rate of 0.05-0.32% in patients who are hospitalized. It is predominantly observed in males and in older patients—in particular, elderly patients with multiple medical problems. The average age of patients from 9 studies was 72 years.

Patients with MAT frequently have significant comorbidities, especially chronic obstructive pulmonary disease (COPD) and respiratory failure, and are often treated in ICUs. Consequently, a high mortality rate (ie, up to 45%) is associated with this arrhythmia, although it is not a direct consequence of the rhythm abnormality.

MAT is seldom life threatening. The overall clinical picture and symptoms improve when the underlying condition is addressed and MAT is controlled. Morbidity is difficult to quantify because the underlying disease is the primary determinant of complications.

PreviousNextClinical PresentationPatient history

Patients may complain of a variety of symptoms, or more rarely, the disease may be asymptomatic. The most common complaints include the following:

PalpitationsShortness of breathChest painLightheadednessSyncopal episode

These symptoms may be transient.

Physical examination

Physical examination findings are typically related to the underlying disease process and are not specific for MAT. The pulse is rapid and irregular,[2] and the first heart sound may be variable. The physical examination is not typically sufficient to differentiate multifocal atrial tachycardia from atrial fibrillation. Respiratory adventitial sounds often are prominent.

Depending upon comorbid conditions or general health status, the patient may be hemodynamically unstable. However, determining whether this is due to the underlying condition or the dysrhythmia may be difficult.

Complications

Potential acute complications of MAT include the following:

Atrial thrombi with embolization and subsequent strokeMyocardial infarction from incongruous myocardial supply and demandPulmonary emboliUnderlying disorders

COPD is the most common underlying disease process, seen in approximately 60% of MAT cases. MAT is commonly precipitated by exacerbation of COPD, sometimes due to infection or cardiac decompensation. Increasing hypoxemia with respiratory acidosis and advanced disease also leads to increased bronchodilator usage, thereby increasing catecholamine levels, which may contribute to development of MAT.

Patients with MAT frequently have cardiac diseases, mainly coronary artery disease and valvular heart diseases, often in conjunction with COPD. Heart failure is often present when the diagnosis of MAT is first made.

In various series, 24% of patients with MAT were found to have diabetes mellitus. Fourteen percent had hypokalemia, and 14% had azotemia. Twenty-eight percent of patients with MAT were recovering from major surgery, while others had postoperative infections, sepsis, pulmonary embolism, and heart failure.

The link between pulmonary embolism and MAT is weak (ie, 6-14% of such patients have been said to have MAT), but the methods of diagnosing pulmonary embolism have not been well documented.

Experimental evidence demonstrates that IV cocaine use may lead to the development of MAT.

PreviousNextDifferential Diagnosis

The differential diagnosis of MAT includes atrial fibrillation and atrial flutter. Clear differentiation of multifocal atrial tachycardia (MAT) from atrial fibrillation is very important because the treatment of atrial fibrillation differs from that of MAT. MAT with aberration or preexisting bundle branch block may be misinterpreted as ventricular tachycardia. MAT must also be differentiated from other tachyarrhythmias, both narrow-complex and wide-complex, including sinus tachycardia with frequent premature atrial contractions (PACs).

PreviousNextElectrocardiography

The diagnosis of multifocal MAT is confirmed with an ECG that displays the following features (see the image below):

Irregular ventricular rate greater than 100 bpmOrganized and discrete P waves with at least 3 different morphologies in the same electrocardiographic leadIrregular PP, PR, and RR intervals with an isoelectric baseline between the P wavesECG showing multifocal atrial tachycardia (MAT).

Some authors have suggested that patients who have a heart rate less than 100 bpm but who satisfy all other criteria (including the clinical profile commonly observed with MAT) be considered to have multifocal atrial rhythm, or multifocal atrial bradycardia if the rate is less than 60 bpm. There is controversy about whether this condition should be referred to as a MAT variant or a wandering atrial pacemaker, although patients with wandering atrial pacemaker usually do not have serious underlying illnesses.

The requirement that 3 different P waves should exist has been applied since early descriptions of the arrhythmia were recorded, but whether this should be interpreted as 2 ectopic P waves and 1 sinus P wave or 3 ectopic P waves has been a matter of controversy. The consensus favors a minimum of 3 different waveforms in addition to sinus P waves.

Baseline noise on the ECG can mimic atrial fibrillation and can obscure differences in P wave morphology. Conversely, coarse atrial fibrillation on short recordings may appear to show discrete P waves prior to each QRS complex. Longer ECG recordings are therefore useful.

PreviousNextLaboratory Studies

Laboratory testing mainly consists of the following:

Serum chemistry panel to exclude electrolyte disordersBlood hemoglobin level and RBC counts to seek evidence of anemiaArterial blood gases to define pulmonary status

Any further testing depends on the underlying disease process (eg, cardiac biomarkers in patients with coronary artery disease, or a theophylline level if patient has been prescribed, or has access to, this medication).

PreviousNextOther Tests

Consider a portable anteroposterior (AP) chest radiograph to evaluate for pulmonary and cardiac findings, particularly in the unstable patient. All patients should be placed on pulse oximetry and a cardiac monitor.

PreviousNextTreatment of MATPrehospital care

The following measures should be taken in the prehospital setting:

Assess for pulmonary causes that may be causing the arrhythmiaStabilize the acute situation as necessaryProvide oxygen, cardiac monitoring, and pulse oximetryEstablish IV access without delaying transportCollect medications that the patient may be taking or may have access toEmergency department care

Rapidly assess and stabilize the ABCs while providing simultaneous treatment. An upright sitting position usually is most appropriate. Obtain IV access with a large-bore catheter and give isotonic sodium chloride solution at a to-keep-open (TKO) rate.

Administer oxygen to maintain the saturation greater than 90%, but avoid excessive oxygen in patients with known significant chronic obstructive pulmonary disease (COPD). This will avoid the theoretical problem of removing the hypoxic drive for ventilation, which can result in increased carbon dioxide retention.

The need for tracheal intubation is dictated by the standard clinical indications.

Establish cardiac monitor, blood pressure monitor, and pulse oximetry.

Assess for and treat the underlying cardiopulmonary process, theophylline toxicity, or metabolic abnormality. Administer bronchodilators and oxygen for treatment of decompensated COPD; activated charcoal and/or charcoal hemoperfusion is the therapy for theophylline toxicity. When magnesium sulfate is administered to correct hypokalemia, most patients convert to normal sinus rhythm. Avoid sedatives.

Treatment and/or reversal of the precipitating cause may be all that is required for patients with multifocal atrial tachycardia (MAT); however, the arrhythmia may recur if the underlying condition worsens. Moreover, treatment of underlying diseases may sometimes have arrhythmia-promoting effects; for example, theophylline and beta-agonist drugs used in patients with COPD produce an increased catecholamine state. These therapies should be used judiciously.

Calcium channel blockers

Diltiazem[3] and verapamil[4, 5, 6, 7, 8, 9] decrease the atrial activity and slow atrioventricular (AV) nodal conduction, thereby decreasing ventricular rate, but they do not return all patients to normal sinus rhythm. Transient hypotension is the most common adverse effect, which may often be avoided by pretreating the patient with 1 g of intravenous calcium gluconate (10 mL of 10% calcium gluconate).

Diltiazem may be used as a 20-45 mg intravenous bolus and then as a 10-25 mg/h continuous infusion. Verapamil may worsen hypoxemia by negating the hypoxic pulmonary vasoconstriction in underventilated alveoli; this is usually not clinically significant.

Beta-blockers

More patients convert to a normal sinus rhythm when treated with beta-blockers. However, the use of beta-blockers is limited by transient hypotension and by bronchospastic adverse effects, since lung disease is commonly associated with MAT.

Metoprolol[6, 8, 10, 11, 12] has been used to lower the ventricular rate. Both oral and intravenous dosage forms have been used. The oral dosage is 25 mg q6h until the desired effects are obtained. Intravenous bolus dosing has been administered to as much as 15 mg over 10 minutes.

Although no controlled studies have evaluated the use of short-acting beta-blockers in treatment of MAT, esmolol can also be used to control the ventricular rate as an intravenous infusion. It has a very short half-life and can be terminated quickly in the event of an adverse reaction.

Magnesium

In a small number of patients, high-dose magnesium[6, 13, 14, 15, 16] causes a significant decrease in the patient's heart rate and conversion to normal sinus rhythm. The dosage is 2 g intravenously over 1 minute, followed by 2 g/h infusion over 5 hours.

Antiarrhythmics

Amiodarone[17, 18, 19] (300 mg PO tid or 450-1500 mg IV over 2-24 h) has been used and has been reported to be associated with conversion to normal sinus rhythm. The success rate was 40% at 3 days with oral dosing and 75% on day 1 with intravenous dosing; however, this has been evaluated in a very small number of patients. Recent data support the use of amiodarone prophylactically postoperatively in patients with COPD. Case reports have also supported the use of ibutilide[20] and flecainide[21] for cardioversion.

Digitalis

Despite the urge to use digoxin, it has not been found to be effective in controlling the ventricular rate or restoring normal sinus rhythm. Digoxin promotes afterdepolarizations, which may promote the arrhythmia. Ventricular arrhythmias, AV block, and death have been reported when excessive digoxin has been administered to patients who were incorrectly diagnosed with atrial fibrillation.

Cardioversion

Cardioversion is contraindicated in MAT. Due to the multiple atrial foci, direct current (DC) cardioversion is not effective in restoring normal sinus rhythm and can precipitate more dangerous arrhythmias.

Surgical care

In patients who have persistent and recurrent episodes of MAT and problems with rate control, the AV node may be ablated using radiofrequency energy and a permanent pacemaker implanted.[22] This approach should be considered both for symptomatic and hemodynamic improvement and to prevent the development of tachycardia-mediated cardiomyopathy.

Consultations

A cardiologist may be of assistance with ECG interpretation and may be available for consultation if antiarrhythmic therapy is being considered.

Inpatient care

Most patients with MAT require admission to further manage their underlying cardiopulmonary diseases. These patients frequently are admitted to a monitored bed; however, the clinical scenario and the hemodynamic stability of the patient dictate disposition.

Further outpatient care

Patients who convert to normal sinus rhythm after treatment and stabilization of the underlying process or provision of specific antiarrhythmic therapy may be cautiously considered for discharge. In order to be discharged, the patient must be back to baseline condition, have no complicating factors, be able to accomplish activities of daily living, and be available for close follow-up care.

Deterrence/prevention

The best means of prevention of MAT is prevention of respiratory failure plus careful monitoring of all electrolyte disorders, namely, hypokalemia, hypomagnesemia, and drug therapy (mainly digoxin toxicity). In patients receiving theophylline, careful monitoring of drug levels is important in order to avoid toxicity.

Patient education

Education about the causes of this arrhythmia may be beneficial. In the case of a pulmonary source, education about prevention and recognition of developing pulmonary conditions may be helpful. In the case of MAT related to medication use, education regarding the correct use and how to monitor such medications should be considered.

Previous, Multifocal Atrial Tachycardia

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Premature Ventricular Contraction

Background

Premature ventricular contraction (PVC) is caused by an ectopic cardiac pacemaker located in the ventricle. PVCs are characterized by premature and bizarrely shaped QRS complexes usually wider than 120 msec on with the width of the ECG. These complexes are not preceded by a P wave, and the T wave is usually large, and its direction is opposite the major deflection of the QRS.

The clinical significance of PVCs depends on their frequency, complexity, and hemodynamic response.

For additional information, see Medscape's Cardiology Specialty page.

NextPathophysiology

Premature ventricular contractions (PVCs) reflect activation of the ventricles from a site below the atrioventricular node (AVN). Suggested mechanisms for PVCs are reentry, triggered activity, and enhanced automaticity.

Reentry occurs when an area of 1-way block in the Purkinje fibers and a second area of slow conduction are present. This condition is frequently seen in patients with underlying heart disease that creates areas of differential conduction and recovery due to myocardial scarring or ischemia. During ventricular activation, the area of slow conduction activates the blocked part of the system after the rest of the ventricle has recovered, resulting in an extra beat. Reentry can produce single ectopic beats, or it can trigger paroxysmal tachycardia.

Triggered beats are considered to be due to after-depolarizations triggered by the preceding action potential. These are often seen in patients with ventricular arrhythmias due to digoxin toxicity and reperfusion therapy after myocardial infarction (MI).

Enhanced automaticity suggests an ectopic focus of pacemaker cells in the ventricle that has a subthreshold potential for firing. The basic rhythm of the heart raises these cells to threshold, which precipitates an ectopic beat. This process is the underlying mechanism for arrhythmias due to excess catecholamines and some electrolyte deficiencies, particularly hyperkalemia.

Ventricular ectopy associated with a structurally normal heart most commonly occurs from the right ventricular outflow tract beneath the pulmonic valve. The mechanism is thought to be enhanced automaticity versus triggered activity. These arrhythmias are often induced by exercise, isoproterenol (in the EP lab), the recovery phase of exercise, or hormonal changes in female patients (pregnancy, menses, menopause). The characteristic ECG pattern for these arrhythmias is a large, tall R wave in the inferior leads with a left bundle-branch block pattern in V 1 . If the source is the left ventricular outflow tract, there is a right bundle-branch block pattern in V 1 . Beta-blocker therapy is first-line therapy if symptomatic.

Factors that increase the risk of PVCs include male sex, advanced age, African American race, hypertension and underlying ischemic heart disease, a bundle-branch block on 12-lead ECG, hypomagnesemia, and hypokalemia.

PreviousNextEpidemiologyFrequencyUnited States

Premature ventricular contractions (PVCs) are one of the most common arrhythmias and can occur in patients with or without heart disease. The prevalence of PVCs varies greatly, with estimates of less than 3% to more than 60% in asymptomatic individuals.

Data from large, population-based studies indicate that the prevalence ranges from less than 3% for young white women without heart disease to almost 20% for older African American individuals with hypertension.

Mortality/Morbidity

The clinical significance of premature ventricular contractions (PVCs) depends on the clinical context in which they occur.

PVCs in young, healthy patients without underlying structural heart disease are usually not associated with any increased rate of mortality. PVCs in older patients, in particular those with underlying heart disease, are associated with an increased risk of adverse cardiac events, particularly sustained ventricular dysrhythmias and sudden death. In patients who have had a MI, the risk of malignant ventricular arrhythmias and sudden death is related to the complexity and frequency of the PVCs. Patients with PVCs in Lown classes 3-5 are at greatest risk (see Lown grading criteria below). Frequent PVCs may be associated with increased risk of stroke in patients who do not have hypertension and diabetes.[1] Race

African American race is associated with an increased frequency of PVCs on routine monitoring.[2] In a large population-based study of PVC prevalence, African American race alone increased the risk of PVCs by 30% compared with the risk in white individuals.

Sex

Ventricular ectopy is more prevalent in men than in women of the same age. Male sex alone increases the risk of identifying PVCs on routine screening, with an odds ratio for male sex of 1.39 compared with women.

Age

PVC frequency increases with age, reflecting the increased prevalence of hypertension and cardiac disease in aging populations.

PreviousProceed to Clinical Presentation , Premature Ventricular Contraction

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Pediatric Tachycardia

Background

Tachycardia is an abnormal rapidity of heart action that usually is defined as a heart rate more than 100 beats per minute (bpm) in adults. In children, the normal heart rate is age dependent, and the definition of tachycardia varies, as shown below.[1, 2]

Age 1-2 days - 123-159 bpmAge 3-6 days - 129-166 bpmAge 1-3 weeks - 107-182 bpmAge 1-2 months - 121-179 bpmAge 3-5 months - 106-186 bpmAge 6-11 months - 109-169 bpmAge 1-2 years - 89-151 bpmAge 3-4 years - 73-137 bpmAge 5-7 years - 65-133 bpmAge 8-11 years - 62-130 bpmAge 12-15 years - 60-119 bpmNextPathophysiology

The heart is innervated primarily by the vagus nerve and the sympathetic ganglion. Pain sensation travels through afferent fibers associated with the sympathetic ganglia. In most patients, the sensation of a normal heartbeat is not felt. Some children may complain of palpitations or rushing or pounding in the ears.

PreviousProceed to Clinical Presentation , Pediatric Tachycardia

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Pulseless Electrical Activity

Background

Pulseless electrical activity (PEA) is a clinical condition characterized by unresponsiveness and lack of palpable pulse in the presence of organized cardiac electrical activity. Pulseless electrical activity has previously been referred to as electromechanical dissociation (EMD). (See Etiology.)

While a lack of ventricular electrical activity always implies a lack of ventricular mechanical activity (asystole), the reverse is not always true. In other words, electrical activity is a necessary, but not sufficient, condition for mechanical activity. In a situation of cardiac arrest, the presence of organized ventricular electrical activity is not necessarily accompanied by meaningful ventricular mechanical activity. The qualifier “meaningful” is used to describe a degree of ventricular mechanical activity that is sufficient to generate a palpable pulse.

PEA does not mean mechanical quiescence. Patients may have weak ventricular contractions and recordable aortic pressure (pseudo-PEA). True PEA is a condition in which cardiac contractions are absent in the presence of coordinated electrical activity. PEA encompasses a number of organized cardiac rhythms, including supraventricular rhythms (sinus versus nonsinus) and ventricular rhythms (accelerated idioventricular or escape). The absence of peripheral pulses should not be equated with PEA, as it may be due to severe peripheral vascular disease. (See Etiology, Clinical, and Workup.)

NextEtiology

Pulseless electrical activity (PEA) occurs when a major cardiovascular, respiratory, or metabolic derangement results in the inability of cardiac muscle to generate sufficient force in response to electrical depolarization. PEA is always caused by a profound cardiovascular insult (eg, severe prolonged hypoxia or acidosis or extreme hypovolemia or flow-restricting pulmonary embolus).

The initial insult weakens cardiac contraction, and this situation is exacerbated by worsening acidosis, hypoxia, and increasing vagal tone. Further compromise of the inotropic state of the cardiac muscle leads to inadequate mechanical activity, even though electrical activity is present. This event creates a vicious cycle, causing degeneration of the rhythm and subsequent death of the patient.

Transient coronary occlusion usually does not cause PEA, unless hypotension or other arrhythmias are involved.

Hypoxia secondary to respiratory failure is probably the most common cause of PEA, with respiratory insufficiency accompanying 40-50% of PEA cases. Situations that cause sudden changes in preload, afterload, or contractility often result in PEA.

Decreased preload

Cardiac sarcomeres require an optimal length (ie, preload) for an efficient contraction. If this length is unattainable because of volume loss or pulmonary embolus (causing decreased venous return to the left atrium), the left ventricle is unable to generate sufficient pressure to overcome its afterload. Volume loss resulting in PEA is most likely to happen in cases of major trauma. In these situations, rapid blood loss and subsequent hypovolemia can exhaust cardiovascular compensatory mechanisms, culminating in PEA. Cardiac tamponade may also cause decreased ventricular filling.

Increased afterload

Afterload is inversely related to cardiac output. Severe increases in afterload pressure cause a decrease in cardiac output. However, this mechanism is rarely solely responsible for PEA.

Decreased contractility

Optimal myocardial contractility depends on optimal filling pressure, afterload, and the presence and availability of inotropic substances (eg, epinephrine, norepinephrine, or calcium). Calcium influx and binding to troponin C is essential for cardiac contraction. If calcium is not available (eg, calcium channel blocker overdose) or if calcium's affinity to troponin C is decreased (as in hypoxia), contractility suffers.

Depletion of intracellular adenosine triphosphate (ATP) reserves causes an increase in adenosine diphosphate (ADP), which can bind calcium, further reducing energy reserves. Excess intracellular calcium can result in reperfusion injury by causing severe damage to the intracellular structures, predominantly the mitochondria.

Additional etiologic factors

PEA can be classified by a number of criteria. While an exhaustive enumeration of causes has the advantage of completeness, it is not a convenient tool at the bedside. The American Heart Association (AHA) and European Resuscitation Council favor the mnemonic of “Hs and Ts” as follows:

HypovolemiaHypoxiaHydrogen ion (acidosis)Hypokalemia/hyperkalemiaHypoglycemiaHypothermiaToxinsCardiac tamponadeTension pneumothoraxThrombosis (coronary or pulmonary)Trauma

The above enumeration of causes does not offer any cues regarding the frequency or reversibility of each cause. As such, it may be not particularly useful, even for those who have committed it to memory.

The "3 and 3 rule" of Desbiens[1] is more practical, because it allows easy recall of the most common correctable causes of PEA. It organizes PEA causes into 3 major ones:

Severe hypovolemiaPump failureObstruction to circulation

The 3 main causes of obstruction to circulation are as follows:

Tension pneumothorax[2] Cardiac tamponade[3] Massive pulmonary embolus[4]

Pump failure is the result of massive myocardial infarction, with or without cardiac rupture, and severe heart failure. Major trauma can be responsible for hypovolemia, tension pneumothorax, or cardiac tamponade.

Metabolic derangements (acidosis, hyperkalemia, hypokalemia), while rarely the initiators of PEA, are common contributing factors. Drug overdose (tricyclic antidepressants, digitalis, calcium channel and beta blockers) or toxins are also rare causes of PEA.[5] Hypothermia should be considered in the appropriate clinical context of out-of-hospital PEA.

Postdefibrillation PEA is characterized by the presence of organized electrical activity, occurring immediately after electrical cardioversion in the absence of palpable pulse. Postdefibrillation PEA may be associated with a better prognosis than continued ventricular fibrillation. A spontaneous return of pulse is likely, and cardiopulmonary resuscitation (CPR) should be continued for as long as 1 minute to allow for spontaneous recovery.

PreviousNextEpidemiologyOccurrence in the United States

The frequency of pulseless electrical activity (PEA) varies among different patient populations. The condition accounts for approximately 20% of cardiac arrests that occur outside the hospital.

Raizes et al found that PEA was responsible for 68% of monitored in-hospital deaths and 10% of all in-hospital deaths.[6] Because of the increased disease acuity observed in patients who are admitted, PEA may be more likely to occur in patients who are hospitalized. Also, these patients are more likely to have pulmonary emboli and such conditions as ventilator-induced auto–PEEP (positive–end-expiratory pressure). PEA is the first documented rhythm in 32-37% of adults with inhospital cardiac arrest.[7, 8]

The use of beta-blockers and calcium channel blockers may increase the frequency of PEA, presumably by interfering with cardiac contractility.

Sex- and age-related demographics

Females are more likely to develop PEA than males. The reasons for this predilection are unclear but may relate to different etiologies of cardiac arrest

The average patient age is 70 years. Older patients are more likely to have PEA as an etiology of cardiac arrest. Whether the patient outcome differs based on age is not known; however, advanced age is likely associated with a worse outcome.

PreviousNextPrognosis

The overall prognosis for patients with pulseless electrical activity (PEA) is poor unless a rapidly reversible cause is identified and corrected. Evidence suggests that electrocardiogram (ECG) characteristics are related to the patient's prognosis. The more abnormal the ECG characteristics, the less likely the patient is to recover from PEA; patients with a wider QRS (>0.2 s) fare worse.

Interestingly, patients with out-of-hospital PEA are more likely to recover than are patients who develop this condition in the hospital. In one study, 98 of 503 (19.5%) patients survived out-of-hospital PEA. This difference is likely because of different etiologies and severity of illness. Patients who are not in the hospital are more likely to have reversible etiologies (eg, hypothermia).

Overall, PEA remains a poorly understood entity with a dismal prognosis. Reversing this otherwise lethal condition may be possible by aggressively seeking and promptly correcting reversible causes.

The Oregon Sudden Unexpected Death Study, which included more than 1,000 cases of patients who presented with PEA (vs ventricular fibrillation), indicated a significantly higher prevalence of syncope that was distinct from cases of ventricular fibrillation. Potential links between future manifestations of PEA and syncope should be investigated further.[9]

Mortality

The overall mortality rate is high in patients in whom PEA is the initial rhythm during cardiac arrest. In a study by Nadkarni et al, only 11.2% of patients who had PEA as their first documented rhythm survived to hospital discharge.[7] In a study by Meaney et al, patients with PEA as the first documented rhythm had a lower rate of survival to discharge than did patients who had ventricular fibrillation or ventricular tachycardia as their first documented rhythm.[8]

Given this grim outlook, the rapid initiation of advanced cardiac life support (ACLS) and identification of a reversible cause are critical. Initiation of ACLS may improve patient outcome if a reversible cause is identified and rapidly corrected.

PreviousProceed to Clinical Presentation , Pulseless Electrical Activity

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Long QT Syndrome

Practice Essentials

Long QT syndrome is a congenital disorder characterized by a prolongation of the QT interval on electrocardiograms and a propensity to ventricular tachyarrhythmias, which may lead to syncope, cardiac arrest, or sudden death.

Essential update: Single vs multiple mutations in long QT syndrome and risk for life-threatening cardiac events

In a recent analysis of 403 patients from the LQTS Registry, investigators found that 57 patients with multiple mutations (≥2 mutations in ≥1 LQTS-susceptibility gene) were at greater risk for life-threatening cardiac events—aborted cardiac arrest, implantable defibrillator shock, or sudden cardiac death—than patients with a single mutation.[1] This finding was borne out in multivariate analyses: Patients with multiple mutations had a 2.3-fold increased risk for life-threatening cardiac events compared with those with a single mutation. Moreover, multiple mutations in a single LQTS gene were associated with a 3.2-fold increased risk, whereas the risk in patients with multiple mutations involving more than 1 LQTS gene did not significantly differ from that seen in patients with a single mutation.[1]

Signs and symptoms

Long QT syndrome is usually diagnosed after a person has a cardiac event (eg, syncope, cardiac arrest). In some situations, this condition is diagnosed after a family member suddenly dies. In some individuals, the diagnosis is made when an electrocardiogram shows QT prolongation.

A history of cardiac events is the most typical clinical presentation in patients with LQTS.

See Clinical Presentation for more detail.

Diagnosis

Findings on physical examination usually do not indicate a diagnosis of long QT syndrome, although some patients may present with excessive bradycardia for their age, and some patients may have hearing loss (congenital deafness), indicating the possibility of Jervell and Lange-Nielsen syndrome. Skeletal abnormalities, such as short stature and scoliosis are seen in the LQT7 type (Andersen syndrome), and congenital heart diseases, cognitive and behavioral problems, musculoskeletal diseases, and immune dysfunction may be seen in those with LQT8 type (Timothy syndrome).

Testing

Diagnostic studies in patients with suspected long QT syndrome include the following:

Serum potassium and magnesium levelsThyroid function testsElectrocardiography of the patient and family membersPharmacologic provocation with epinephrine or isoproterenol in patients with a borderline presentationGenetic testing of the patient and family members

An increased QTc interval in response to standing up (“response to standing” test), which is associated with increased sympathetic tone, can provide more diagnostic information in patients with long QT syndrome.[2] This increase in QTc in response to standing may persist in these patients even after heart rate returns to normal.[3]

See Workup for more detail.

Management

No treatment addresses the cause of long QT syndrome. Antiadrenergic therapeutic measures (eg, use of beta-blockers, left cervicothoracic stellectomy) and device therapy (eg, use of pacemakers, implantable cardioverter-defibrillators) aim to decrease the risk and lethality of cardiac events.

Pharmacotherapy

Beta-adrenergic blocking agents are the drugs of choice to treat long QT syndrome and include the following medications:

PropranololNadololMetoprololAtenolol

Surgical option

Surgical intervention in patients with long QT syndrome may include the following procedures:

Implantation of cardioverter-defibrillatorsPlacement of a pacemakerLeft cervicothoracic stellectomy

Nonpharmacotherapy

Patients with long QT syndrome should avoid participation in competitive sports, strenuous exercise, and stress-related emotions.

These individuals should also avoid the following agents:

Anesthetics or asthma medication (eg, epinephrine)Antihistamines (eg, diphenhydramine; terfenadine and astemizole [both recalled from US market])Antibiotics (eg, erythromycin, trimethoprim and sulfamethoxazole, pentamidine)Cardiac medications (eg, quinidine, procainamide, disopyramide, sotalol, probucol, bepridil, dofetilide, ibutilide)Gastrointestinal medications (eg, cisapride)Antifungal medications (eg, ketoconazole, fluconazole, itraconazole)Psychotropic medications (eg, tricyclic antidepressants, phenothiazine derivatives, butyrophenones, benzisoxazole, diphenylbutylpiperidine)Potassium-loss medications (eg, indapamide, other diuretics; medications for vomiting/diarrhea)

See Treatment and Medication for more detail.

Image libraryMarked prolongation of QT interval in a 15-year-old male adolescent with long QT syndrome (LQTS) (R-R = 1.00 s, QT interval = 0.56 s, QT interval corrected for heart rate [QTc] = 0.56 s). Abnormal morphology of repolarization can be observed in almost every lead (ie, peaked T waves, bowing ST segment). Bradycardia is a common feature in patients with LQTS. NextBackground

Long QT syndrome (LQTS) is a congenital disorder characterized by a prolongation of the QT interval on electrocardiograms (ECGs) and a propensity to ventricular tachyarrhythmias, which may lead to syncope, cardiac arrest, or sudden death. (See Etiology, Prognosis, Presentation, and Workup.)

The QT interval on the ECG, measured from the beginning of the QRS complex to the end of the T wave, represents the duration of activation and recovery of the ventricular myocardium. A QT interval corrected for heart rate (QTc) that is longer than 0.44 seconds is generally considered to be abnormal, although a normal QTc can be more prolonged in females (up to 0.46sec). The Bazett formula is the formula most commonly used to calculate the QTc, as follows: QTc = QT/square root of the R-R interval (in seconds). (See Workup.)

To measure the QT interval accurately, the relationship of QT to the R-R interval should be reproducible. This issue is especially important when the heart rate is under 50 beats per minute (bpm) or over 120 bpm and when athletes or children have marked beat-to-beat variability of the R-R interval. In such cases, long recordings and several measurements are required. The longest QT interval is usually observed in the right precordial leads. When marked variation is present in the R-R interval (atrial fibrillation, ectopy), correction of the QT interval is difficult to define precisely. (See Workup.)

PreviousNextEtiology and Pathophysiology

The QT interval represents the duration of activation and recovery of the ventricular myocardium. Prolonged recovery from electrical excitation increases the likelihood of dispersing refractoriness, when some parts of myocardium might be refractory to subsequent depolarization.

From a physiologic standpoint, dispersion occurs with repolarization between 3 layers of the heart, and the repolarization phase tends to be prolonged in the mid myocardium. This is why the T wave is normally wide and the interval from Tpeak to Tend (Tp-e) represents the transmural dispersion of repolarization (TDR). In long QT syndrome (LQTS), TDR increases and creates a functional substrate for transmural reentry.

LQTS has been recognized as mainly Romano-Ward syndrome (ie, familial occurrence with autosomal dominant inheritance, QT prolongation, and ventricular tachyarrhythmias) or as Jervell and Lang-Nielsen (JLN) syndrome (ie, familial occurrence with autosomal recessive inheritance, congenital deafness, QT prolongation, and ventricular arrhythmias). Two other syndromes are described, namely, Andersen syndrome and Timothy syndrome, although there is some debate on whether they should be included in LQTS.

Torsade de pointes

In LQTS, QT prolongation can lead to polymorphic ventricular tachycardia, or torsade de pointes, which itself may lead to ventricular fibrillation and sudden cardiac death. Torsade de pointes is widely thought to be triggered by reactivation of calcium channels, reactivation of a delayed sodium current, or a decreased outward potassium current that results in early afterdepolarization (EAD), in a condition with enhanced TDR usually associated with a prolonged QT interval. TDR serves as a functional reentry substrate to maintain torsade de pointes.

TDR not only provides a substrate for reentry but also increases the likelihood of EAD, the triggering event for torsade de pointes, by prolonging the time window for calcium channels to remain open. Any additional condition that accelerates the reactivation of calcium channels (eg, increased sympathetic tone) increases the risk of EAD.

Genetics

LQTS is known to be caused by mutations of the genes for cardiac potassium, sodium, or calcium ion channels; at least 10 genes have been identified. Based on this genetic background, 6 types of Romano-Ward syndrome, 1 type of Andersen syndrome and 1 type of Timothy syndrome, and 2 types of JLN syndrome are characterized (see Table 1, below).

LQTS results from mutations of genes encoding for cardiac ion channel proteins, which cause abnormal ion channel kinetics. Shortened opening of the potassium channel in LQT1, LQT2, LQT5, LQT6, JLN1, and JLN2 and delayed closing of a sodium channel in LQT3 overcharges a myocardial cell with positive ions. At least 10 genes have been identified in LQTS.

Table 1. Genetic Background of Inherited Forms of LQTS (Romano-Ward syndrome: LQT1-6, Anderson syndrome: LQT7, Timothy syndrome: LQT8, and Jervell and Lang-Nielsen syndrome: JLN1-2) (Open Table in a new window)

Type of LQTS Chromosomal Locus Mutated Gene Ion Current Affected LQT111p15.5KVLQT1 or KCNQ1 (heterozygotes)Potassium (IKs)LQT27q35-36HERG, KCNH2Potassium (IKr)LQT33p21-24SCN5ASodium (INa)LQT44q25-27ANK2, ANKBSodium, potassium and calciumLQT521q22.1-22.2KCNE1 (heterozygotes)Potassium (IKs)LQT621q22.1-22.2MiRP1, KNCE2Potassium (IKr)LQT7 (Anderson syndrome)17q23.1-q24.2KCNJ2Potassium (IK1)LQT8 (Timothy syndrome)12q13.3CACNA1CCalcium (ICa-Lalpha)LQT93p25.3CAV3Sodium (INa)LQT1011q23.3SCN4BSodium (INa)LQT117q21-q22AKAP9Potassium (IKs)LQT12SNTAISodium (INa)JLN111p15.5KVLQT1 or KCNQ1 (homozygotes)Potassium (IKs)JLN221q22.1-22.2KCNE1 (homozygotes)Potassium (IKs)

LQT1, LQT2, and LQT3 account for most cases of LQTS, with estimated prevalences of 45%, 45%, and 7%, respectively. In LQTS, QT prolongation is due to overload of myocardial cells with positively charged ions during ventricular repolarization. In LQT1, LQT2, LQT5, LQT6, and LQT7, potassium ion channels are blocked, they open with a delay, or they are open for a shorter period than they are in normally functioning channels. These changes decrease the potassium outward current and prolong repolarization.

LQT1

The LQT1 gene (KVLQT1 or KCNQ1) encodes for part of the IKs slowly deactivating, delayed rectifier potassium channel. More than 170 mutations (most missense) of this gene have been reported. Their net effect is a decreased outward potassium current. Therefore, the channels remain open longer than usual, with a delay in ventricular repolarization and with QT prolongation.

LQT2

The LQT2 gene (HERG or KCNH2) encodes for part of IKr rapidly activating, rapidly deactivating, delayed rectifier potassium channel. Mutations in this gene cause rapid closure of the potassium channels and decrease the normal rise in IKr. They also result in delayed ventricular repolarization and QT prolongation. About 200 mutations in this gene have been detected.

LQT3

In LQT3, caused by mutations of the SCN5A gene for the sodium channel, a gain-of-function mutation causes persistent inward sodium current in the plateau phase, which contributes to prolonged repolarization. Some loss-of-function mutations in the same gene may lead to different presentations, including Brugada syndrome. More than 50 mutations have been identified in this gene.

In some patients, caveolae proteins have been recognized as responsible for the increased Na+ current in LQTS3.[4] Caveolae are small (50-100 nm) microdomains that exist on the membrane of a variety of cells, including cardiac myocytes and fibroblasts. Some ion channels, and in particular the SCN5A -encoded voltage-gated Na+ channels, are mainly colocalized with caveolae on the membrane. Thus, absence or abnormal formation of caveolae may have some effects on the availability of Na+ channels. For instance, Vatta and colleagues demonstrated that mutations in caveolin-3 protein exist in LQTS3 and that they can cause an increase in late Na+ current.[4]

Nevertheless, caveolae are present in the membrane of many other cell types and are involved in many cellular activities, thus, their impairment is expected to be associated with multisystemic diseases.

For example, Rajab and colleagues reported genetic mutations resulting in defective caveolae in families with congenital generalized lipodystrophy who have several systemic manifestations, such as hypertrophic pyloric stenosis, impaired bone formations, ventricular arrhythmia, and sudden cardiac death.[5] The fact that mutations in proteins associated with ion channels may result in change in the availability of channels on the membrane, and therefore a significant change in total current, has added a new window for investigating the genetic abnormalities resulting in LQTS.

LQT4 gene

The LQT4 gene (ANK2 or ANKB) encodes for the ankyrin-B. Ankyrins are adapter proteins that bind to several ion channel proteins, such as the anion exchanger (chloride-bicarbonate exchanger), sodium-potassium adenosine triphosphatase (ATPase), the voltage-sensitive sodium channel (INa), the sodium-calcium exchanger (NCX, or INa-Ca), and calcium-release channels (including those mediated by the receptors for inositol triphosphate [IP3] or ryanodine).

Mutations in this gene interfere with several of these ion channels. The end result is increased intracellular concentration of calcium and, sometimes, fatal arrhythmia. Five mutations of this gene are reported. LQT4 is interesting because it provides an example of how mutations in proteins other than ion channels can be involved in the pathogenesis of LQTS.

LQT5, 6, 7, 8, 9, 10

The LQT5 gene encodes for the IKs potassium channel. Similar to LQT1, LQT5 results in a decreased outward current of potassium and in QT prolongation.

LQT6 involves mutations in the gene MiRP1, or KCNE2, which encodes for the potassium channel beta subunit MinK-related protein 1 (MiRP1). KCNE2 encodes for beta subunits of IKr potassium channels.

The LQT7 gene (KCNJ2) encodes for potassium channel 2 protein that plays an important role in inward repolarizing current (IKi), especially in phase 3 of the action potential. In this subtype, QT prolongation is less prominent than in other types, and the QT interval is sometimes in the normal range. Because potassium channel 2 protein is expressed in cardiac and skeletal muscle, Andersen syndrome is associated with skeletal abnormalities, such as short stature and scoliosis.

Mutations in the LQT8 gene (CACNA1C) cause loss of L-type calcium current. So far, a limited number of cases of Timothy syndrome have been reported. They have been associated with abnormalities such as congenital heart disease, cognitive and behavioral problems, musculoskeletal diseases, and immune dysfunction.

The LQT9 gene encodes for caveolin 3, a caveolae plasma membrane component protein involved in scaffolding proteins. The voltage-gated sodium channel (NaV b3) is associated with this protein. Functional studies have demonstrated that CAV3 mutations are associated with persistent late sodium current and have been reported in cases of sudden infant death syndrome (SIDS).[6] LQT9 and LQT4 serve as examples of LQTS with nonchannel mutations.

A novel mutation in the LQTS10 gene encoding the protein NaV b4, a subunit of the voltage-gated sodium channel of the heart, NaV 1.5 (gene SCN5), results in a positive shift in the inactivation of the sodium current. To date, only a single mutation in 1 patient has been described.[7]

Alpha-1-syntrophic gene mutation

The newest genetic missense mutation associated with LQTS has been described in the alpha-1-syntrophin gene and results in gain of function of the sodium channel similar to that observed in LQT3.[8]

Stimuli

In patients with LQTS, a variety of adrenergic stimuli, including exercise, emotion, loud noise, and swimming, may precipitate an arrhythmic response. However, it also may occur without such preceding conditions.

Drug-induced QT prolongation

Secondary (drug-induced) QT prolongation may also increase the risk of ventricular tachyarrhythmias (eg, torsade de pointes) and sudden cardiac death. The ionic mechanism is similar to that observed in congenital LQTS; ie, mainly intrinsic blockade of cardiac potassium efflux.

In addition to the medications that potentially can prolong the QT interval, several other factors play a role in this phenomenon. Important risk factors for drug-induced QT prolongation include the following:

Female sexElectrolyte disturbances (hypokalemia and hypomagnesemia)HypothermiaAbnormal thyroid functionStructural heart diseaseBradycardia

Drug-induced QT prolongation also may have a genetic background, consisting of the predisposition of an ion channel to abnormal kinetics caused by gene mutation or polymorphism. However, data are insufficient to claim that all patients with drug-induced QT prolongation have a genetic LQTS-related mechanism. Arizona CERT provides lists of Drugs that Prolong the QT Interval and/or Induce Torsades de Pointes Ventricular Arrhythmia.

PreviousNextEpidemiologyOccurrence in the United States

Long QT syndrome (LQTS) remains an underdiagnosed disorder, especially because at least 10-15% of LQTS gene carriers have a normal QTc duration.

The prevalence of LQTS is difficult to estimate. However, given the currently increasing frequency of diagnosis, LQTS may be expected to occur in 1 in 10,000 individuals.

International occurrence

The occurrence of long QT syndrome internationally is similar to that in the United States.

Sex-related demographics

Newly diagnosed cases of LQTS are more prevalent in female patients (60-70% of cases) than in male patients. The female predominance may be related to the relatively prolonged QTc (as determined by using the Bazett formula) in women compared with men and to a relatively higher mortality rate in young men.

In women, pregnancy is not associated with an increased incidence of cardiac events, whereas the postpartum period is associated with a substantially increased risk of cardiac events, especially in the subset of patients with LQT2. Cardiac events have been highly correlated with menses.

Also, a significantly higher risk of cardiac events (a 3-fold to 8-fold increase, mainly in the form of recurrent episodes of syncope) has been reported in women with LQT2 syndrome during and after the onset of menopause, compared with the reproductive years.[9]

Age-related demographics

Patients with LQTS usually present with cardiac events (eg, syncope, aborted cardiac arrest, sudden death) in childhood, adolescence, or early adulthood. However, LQTS has been identified in adults as late as in the fifth decade of life. The risk of death from LQTS is higher in boys than in girls younger than 10 years; the risk is similar in male and female patients thereafter.

PreviousNextPrognosis

The prognosis for patients with long QT syndrome (LQTS) treated with beta-blockers (and other therapeutic measures, if needed) is good overall. Fortunately, episodes of torsade de pointes are usually self-terminating in patients with LQTS; only about 4-5% of cardiac events are fatal.

Patients at high risk (ie, those with aborted cardiac arrest or recurrent cardiac events despite beta-blocker therapy) have a markedly increased risk of sudden death. Treat these patients with an implantable cardioverter-defibrillator (ICDs); their prognosis after implantation of an ICD is good.

Morbidity and mortality

Mortality, morbidity, and responses to pharmacologic treatment differ in the various types of LQTS. This issue is under investigation.

LQTS may result in syncope and lead to sudden cardiac death, which usually occurs in otherwise healthy young individuals. LQTS is thought to cause about 4000 deaths in the United States each year. The cumulative mortality rate reaches approximately 6% by the age of 40 years.

Although sudden death usually occurs in symptomatic patients, it happens with the first episode of syncope in about 30% of the patients. This occurrence emphasizes the importance of diagnosing LQTS in the presymptomatic period. Depending on the type of mutation present, sudden cardiac death may happen during exercise, emotional stress, at rest, or at sleep. LQT4 is associated with paroxysmal atrial fibrillation.

Studies have shown an improved response to pharmacologic treatment with a lowered rate of sudden cardiac death in LQT1 and LQT2, compared with LQT3.

Neurologic deficits after aborted cardiac arrest may complicate the clinical course after successful resuscitation.

PreviousNextPatient Education

Educate patients regarding the nature of LQTS and factors that trigger cardiac events. Patients should avoid sudden noises (eg, from an alarm clock), strenuous exercise, water activities, and other arousal factors.

Educate patients and family members about the critical importance of systematic treatment with beta-blockers. Advise family members and the patient's teachers at school to undergo training in cardiopulmonary resuscitation (CPR).

Educate patients and family members about medications that may induce QT prolongation and that should be avoided in patients with LQTS. Arizona CERT provides lists of Drugs that Prolong the Qt Interval and/or Induce Torsades de Pointes Ventricular Arrhythmia.

The Sudden Arrhythmia Death Syndromes Foundation (SADS) and Cardiac Arrhythmias Research and Education Foundation (CARE) have support groups for families with LQTS.

PreviousProceed to Clinical Presentation , Long QT Syndrome

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