CHAPTER 25 Sudden Cardiac Death

Definition

Sudden cardiac death (SCD) is defined as a natural and unexpected death as a result of cardiac causes that occur within 1 hour of the onset of new symptoms.¹ In some medical circles, the term “sudden cardiac arrest” (SCA) is preferred because the expression “death” conveys finality of the event, which is not necessarily the outcome in all cases. In this communication, both terms will be used as appropriate in the text.

Epidemiology

Cardiovascular disease-related deaths are still the most common cause of mortality in the United States. The two modes of cardiovascular death (i.e., sudden and nonsudden) are equally common. SCD claims 325,000 lives each year in United States,² thus the incidence is 0.1% to 0.2% annually.³ It is usually ascribed to arrhythmic causes and it is the case the vast majority of the time when the initiation of the episode is electrocardiographically documented. However, the victims are seldom under medical observation, thus the exact mechanism leading to cardiovascular collapse is difficult to establish, and the cause is labeled on the basis of presentation and the earliest onsite ECG recordings. Monitored victims and rescue squads encountering individuals with SCA show the following arrhythmias at the time of arrival: ventricular fibrillation (VF) in 80% of the victims, ventricular tachycardia (VT) in 10% who have the best outcome, and bradycardias in 10%.^4,⁵ The rhythm disturbance first documented by emergency rescue teams is dependent upon the time elapsed after the cardiovascular collapse. VF is seen early after collapse and progresses to asystole as time passes (Fig. 25-1).

Figure 25-1 Fortuitous Holter recording from a patient who experienced sudden cardiac death outside the hospital documents the usual and typical sequence of events. The initial rapid ventricular tachycardia continues into the second panel with widening of the QRS, probably owing to myocardial metabolic changes. Subsequent transformation to ventricular fibrillation is shown in the third panel, followed by asystole. The initial documented rhythm and, ultimately, the prognosis depend on how soon emergency personnel arrive to treat the individual.

(From Akhtar M, Garan H, Lehmann H, et al: Sudden cardiac death: management of high risk patients. Ann Intern Med 1991;114:499.)

For the most part, patients with bradycardia have little or no response to pacing, suggesting hemodynamic collapse as the underlying problem and bradycardia as the concomitant rhythm (electrical-mechanical dissociation). Occasionally, torsades de pointes may be precipitated by severe bradycardia and cause SCA. The universal futility of cardiac pacing in this setting to improve survival in this population, attests to the possibility that overall, one fourth of SCA victims may have nonarrhythmic etiology. Conduction system abnormalities have been labeled as the cause of SCD in younger population victims without demonstrable heart disease in autopsy studies.⁶

While the possibility of SCA can be literally eliminated for previously identified individuals at high risk, the population at large, for now, must contend with the existing sources of aid (emergency medical services, first responders, rescue squads, etc.) that are available in a given community and their relative effectiveness.

In this communication, more space is provided for lesser known but emerging arrhythmia syndromes and the management approach is mostly geared towards internal or external defibrillation devices. The literature is replete with coronary artery disease (CAD) in SCA and its various presentations; work-up, therefore, will only be briefly discussed.

Pathophysiology

SCA may be best considered as the outcome of an interaction between an abnormal cardiac substrate and a transient functional disturbance, which triggers the arrhythmia at a specific point in time. Increasingly, however, it is being recognized that SCA can occur in the absence of any demonstrable structural heart disease. Furthermore, it is coming to light that for many of these primary arrhythmic etiologies there are identifiable genetic mutations, as will be discussed later in this chapter.

Pathologic Substrates

Over the years, numerous studies have revealed that an overwhelming majority of SCA cases (75% to 80%) are due to acute, chronic, or acute on chronic atherosclerotic CAD.¹ The second most frequent category of disorders is cardiomyopathies, which include both hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM). These pathologic substrates are:

1. CAD:

It has been demonstrated that there are one or more active coronary lesions in up to 90% of SCD victims ⁷ that present as an acute, chronic, or acute on chronic process. This association is described as follows:

a. Acute: There is a close association between the occurrence of SCD and the presence of plaque fissuring and/or erosion, platelet aggregation, and acute thrombosis within the matrix of coronary atherosclerosis. However, only 20% of SCD victims have acute myocardial infarction (MI),⁸ likely because the pathophysiologic mechanism leading to that expression is interrupted by an abrupt cessation of the biologic activity because of lethal arrhythmia.⁹

b. Chronic: Myocardial pathology reflects the presence and extent of chronic coronary atherosclerosis, in that myocardial scars, because of healed MIs, are common.¹⁰

2. Left ventricular hypertrophy (LVH) and HCM:

LVH is now a well-established independent risk factor for SCD,¹¹ both in the presence and absence of concomitant CAD. In fact, the majority of SCA victims with CAD have coexisting LVH, although the mortality associated with LVH does not parallel that of CAD. Hypertrophied ventricular myocytes demonstrate altered membrane electrophysiology, resulting in delayed inactivation of slow inward Ca²⁺ currents and delayed activation of K⁺ rectifier currents accounting for recovery of excitability. Transient ischemia and reperfusion make hypertrophied cells susceptible to afterdepolarizations and triggered arrhythmias.¹² One common feature observed in HCM is myocytes disarray, which is common to most, but not all, genetic forms of the disease. The association between HCM expression and SCA risk is complex because of patterns of inheritance involving not only multiple gene foci but mutation-specific risk.⁹

3. DCM:

The underlying myocardial pathology demonstrated in DCM accounts for approximately 10% to 15% of SCD. The pathologic findings are nonspecific, characterized by dilation of the ventricles with interstitial patchy fibrosis, myocytes degeneration, and necrosis.

4. Infiltrative, inflammatory, and valvular diseases:

These account for most of the remaining minority of causes of SCA in patients with structural heart disease. Clinically silent myocarditis has been considered among the more common of the causes of SCD in adolescents and young adults.¹³ The pathologic finding in acute viral myocarditis is high-grade inflammatory processes in the myocardium, but some forms of a viral myocarditis may demonstrate diffuse fibrosis, without inflammatory markers.¹⁴

5. Abnormalities of the cardiac conducting tissue:

They are best exemplified by the Wolff-Parkinson-White syndrome (WPW) and diseases of the His-Purkinje system. Patients with WPW who have pathways with short refractory periods are susceptible to VF during atrial fibrillation/flutter.

6. Genetically determined disorders:

They account for a small proportion of SCDs (1% to 2%), occurring predominantly in adolescents and young adults.

a. Inherited: long Q–T syndromes, short QT syndromes, Brugada syndrome, HCM, right ventricular dysplasia, catecholaminergic polymorphic ventricular tachycardia, progressive cardiac conduction defect, sudden infant death syndrome “SIDS,” and idiopathic ventricular fibrillation “IVF.”^15,¹⁶

b. Not inherited: congenital cardiac lesions (e.g., anomalous coronary arteries) and myocarditis.¹⁷

Functional Modulators

Functional modulators interact with structural abnormalities, converting them from a stable to an unstable state, promoting the start of fatal arrhythmias. Many of the functional modulators (e.g., transient ischemia and acquired long QT), if sufficiently intense, can initiate a fatal arrhythmia in a victim, in the absence of any structural heart disease. However, this is clinically uncommon.

1. Transient ischemia:

It plays a major role in producing fatal arrhythmias. At the cellular level, acute physiologic changes from ischemia include dispersion of both conduction patterns and refractoriness, providing the environment for reentrant arrhythmias and generating abnormal automatic activity. Ischemia opens up the ATP-sensitive K⁺ channels, more in the epicardial than the endocardial cells.¹⁸ This results in heterogeneity in the refractoriness of the two regions, making the myocardium prone to arrhythmias. Reperfusion events may have equally important electrophysiologic consequences. An inward flux of calcium occurs during reperfusion, resulting in overload, and correlates with a burst of spontaneous ventricular ectopy, probably owing to automaticity or triggered activity.

2. Systemic factors:

a. Hemodynamic deterioration:

Acute hemodynamic deterioration may precipitate a secondary cardiac arrest, which unfortunately carries high short-term mortality. The mechanisms could be related to ischemic and metabolic substrates.

b. Electrolyte disturbances:

Hypokalemia has been implicated in an increased risk of sudden and total cardiovascular mortality and plays a particularly important role in the genesis of torsades de pointes and other polymorphic VT.¹⁹

3. Altered systemic autonomic balance:

Structural abnormalities create autonomic disturbances resulting in altered ß-adrenergic receptor content, coupling proteins, and adenylate cyclase activity. This causes dispersion of quantitative and qualitative responses to sympathetic stimulation in the abnormal heart, predisposing to arrhythmias. Clinically, altered systemic autonomic balance is manifested as loss of the normal diurnal variation of heart rate variability, which is considered a marker for risk of SCA among MI and SCA survivors.²⁰

4. Drug toxicity:

Drug toxicity, as a cause of SCA, has been documented in connection with a variety of both cardio-active (antiarrhythmic) and noncardiac drugs, such as psychotropic drugs, erythromycin, Seldane, and pentamidine. A variety of electrophysiologic mechanisms are operative in the genesis of lethal ventricular tachyarrhythmias induced by various drugs. However, there may be concurrent structural or functional abnormalities. The latter include transient ischemia, hemodynamic dysfunction, electrolyte abnormalities, and ventricular hypertrophy. Recently, an increased risk of SCA has been reported with the concomitant use of cocaine and alcohol, and is probably because of the generation of a cardiotoxic metabolite, cocaethylene.²¹

5. Acidosis

6. Hypoxemia

Clinical Substrate

To predict SCA, it is important to recognize the conditions leading to abrupt cessation of cardiac output. Figure 25-2 shows data derived from various studies²²^–²⁶ demonstrating the predominant substrates of SCD. The relative risk for SCD is dependent upon the underlying substrate and is graphically demonstrated for various populations in Figure 25-3.

Figure 25-2 Prevalence of underlying heart disease in adult patients who have experienced sudden cardiac death, based on data derived from several studies,²²^–²⁶ shows coronary artery disease, cardiomyopathies, valvular and hypertensive heart disease, and electrical disturbances as the predominant substrates. CAD, coronary artery disease; CM, cardiomyopathy; HHD, hypertensive heart disease; LQTS, long QT syndrome; SVT, supraventricular tachycardia.

(From Deshpande S, Vora A, Axtell K, Akhtar M: Sudden cardiac death. In Brown DL [ed]: Cardiac Intensive Care. Philadelphia, Saunders, 1998, pp 391-404.)

Figure 25-3 The incidence and number of patients with sudden cardiac death (SCD) in various subgroups of patients. Left, SCD incidence percent per year in each subgroup. Right, Total number of SCDs per year (n × 1000). CAD, coronary artery disease; EF, ejection fraction; Hx, history; MI, myocardial infarction; SCA, sudden cardiac arrest; VF/VT, ventricular fibrillation/ventricular tachycardia.

(Modified from Myerburg RJ Kessler KM, Castellanos A: SCD: Structure, function, and time-dependence of risk. Circulation 1992;85:I-2-I-10.)

Coronary Artery Disease (CAD)

CAD is the most common cause of SCA, where it is the responsible substrate in 65% to 90%²⁷^–³³ of cases. SCA related to coronary events is more common in younger victims, more common in men than in women, and more common in African Americans than in whites. Approximately 20% of SCA victims show evidence of new ST elevation myocardial infarction at the time of cardiac arrest, but 40% to 75% have evidence of healed MI. Fifty percent of post–MI deaths occur in the first 6 months.⁹ Most of the risk factors for CAD are predictors for SCA (e.g., left bundle branch block on ECG, hyperlipidemia, hypertension, cigarette smoking, obesity, diabetes, and lifestyle).³

Nonatherosclerotic CAD

Nonatherosclerotic CAD is also a significant risk for SCA, especially in the younger population. The common nonatherosclerotic coronary artery abnormalities include:

1. Congenital anomalies:

The most common congenital anomaly is the origin of the left main coronary artery from the right sinus of Valsalva, with passage of this vessel between the aorta and the pulmonary trunk.³⁴ Although death is not universal with this anomaly, virtually all such deaths occur during or shortly following vigorous exercise. It is postulated that the left main coronary may be compressed against the root of the pulmonary trunk during exercise when both of these great vessels dilate, thus compromising coronary blood flow and producing myocardial ischemia. Unfortunately, antemortem diagnosis of this anomaly is rare, despite the fact that a significant number of patients experience prodromal symptoms, such as syncope and angina.

Another coronary anomaly that poses risk for SCA in young individuals is the origin of the right coronary artery from the left sinus of Valsalva, with a consequent course between the aorta and pulmonary trunk.³⁵ Some unusual variants of coronary arterial anatomy, including hypoplasia of the right coronary and left circumflex or the anomalous origin of the left anterior descending or right coronary from the pulmonary trunk,³⁶ may in rare instances be implicated in exercise-related sudden cardiac deaths.

2. Embolism:

Coronary artery embolism usually results from endocarditis of the native or prosthetic aortic and mitral valves,³⁷ although rarely, left ventricular or left atrial thrombi may embolize into the coronaries.

3. Arteritis:

Kawasaki disease,³⁸ polyarteritis nodosa,³⁹ and syphilitic aortitis⁴⁰ can affect the coronary circulation, and SCA may be a rare sequelae.

4. Bridging:

SCA has also been reported to occur, especially during exertion, in patients with severe myocardial bridging, particularly of the left anterior descending artery. In this condition, the artery is completely surrounded by myocardium during a portion of its course, instead of being largely epicardial, and a critical degree of systolic compression resulting in myocardial ischemia may occur, even in the absence of underlying atherosclerotic disease.

5. Dissection:

Spontaneous dissection of the coronary arteries in Marfan syndrome ⁴¹ and in the peripartum period of pregnancy,⁴² coronary involvement with any type 1 aortic dissection from other causes, or a rupture of the sinus of Valsalva aneurysm involving the coronary ostia can also cause SCA.⁴³

6. Vasospasm:

Vasospastic angina can have ventricular arrhythmias and culminate in SCA.⁴⁴ This is occasionally an etiology for otherwise unexplained SCA and may also occur as a result of cocaine abuse.

Hypertrophic Cardiomyopathy (HCM)

Despite a relatively low incidence of HCM in the general population, it maintains a high profile risk because 50% to 90% of deaths in patients with HCM are sudden, with an annual mortality rate of 2% to 4%.⁴⁵ Unlike most other heart diseases, the risk of SCA in HCM declines with age.⁴⁶ Patients with this disease characteristically have genetic heterogeneity in the amount of hypertrophy in different regions in the left ventricle. It results from multiple diseased genes, encoding sarcomeric proteins. Microscopically, gross disorganization of muscle bundles and myofibrillar architecture, altered gap junctions, increased basal membrane thickness, and connective tissue accumulation are noted.⁴⁷ These patients, therefore, manifest both electrical instability and consequences of myocardial hypertrophy with altered hemodynamics.

The mortality risk, based on the degree of outflow tract obstruction, has not yet been clearly stratified and, therefore, although hemodynamic considerations may play an important role in SCA, no predictive variables have been identified.⁴⁷ Furthermore, the combination of nonsustained ventricular tachycardia (NSVT) and inducible VT at electrophysiologic testing does confer a higher risk, and, conversely, the absence of NSVT and lack of inducibility indicates a lower risk.

The mechanism for SCA in patients with HCM is most often ventricular arrhythmias.⁴⁸ However, left ventricular outflow obstruction, sinus node dysfunction, atrioventricular (AV) conduction diseases, and supraventricular arrhythmias are alternative mechanisms.⁴⁹ The genesis of these arrhythmias is found in a complex interplay of electrophysiologic and hemodynamic abnormalities, primarily from electrophysiologic derangement of the hypertrophied muscle. Fairly often, SCA is the first manifestation of heart disease in these individuals, and thus is implicated as the substrate explaining the occurrence of these arrhythmias in children or young athletes.⁵⁰ Young age, strong family history, worsening obstructing symptoms,⁵¹ prior episode of SCA, failure to raise blood pressure on exercise, and severe ventricular hypertrophy of more than 3 cm thickness⁵² are incremental risk factors for SCA.

Ventricular hypertrophy secondary to systemic or pulmonary hypertension or owing to valvular or congenital heart disease is also associated with an increased risk for SCA.¹¹ This risk is proportionate to the level of severity of the hypertrophy.⁵³

Idiopathic Dilated Cardiomyopathy (DCM)

Overall survival following a clinical diagnosis of DCM is estimated to be 70% at 1 year and 50% at 2 years.⁵⁴ Most of these deaths are sudden in nature, and the incidence ranges in various series from 28% to 72% of total deaths. Syncope is a poor prognostic indicator in patients with DCM and is associated with a 44% incidence of SCD in 4 years.⁵⁵ Patients with preserved left ventricular function may have a lower short-term mortality from pump failure but are at a greater risk for SCA from arrhythmic events. Ventricular tachyarrhythmias⁵⁶ are the most common mode of death, but bradyarrhythmias⁵⁷ occur also, especially in those patients with advanced pump dysfunction. The arrhythmia most commonly implicated in SCA is primary polymorphic VT or VF. Additionally, rapid sustained monomorphic VT, related to bundle branch reentry,⁵⁸ and monomorphic VT, unrelated to bundle branch re-entry, have been seen. The recognition of this arrhythmia is critical because these patients can be successfully cured by catheter ablation of the right bundle branch.⁵⁸ Catheter ablation, at the present time, cannot be considered a curative option in SCA survivors with ventricular tachycardia related to CAD. Monomorphic VT, unrelated to bundle branch re-entry, is probably the result of the presence of smaller re-entrant circuits within the myocardium. In most instances, the triggering mechanism for the onset of primary polymorphic VT or VF is unclear. In some patients, triggers such as hypokalemia, use of antiarrhythmic medications, and hypomagnesemia may be more easily identifiable.

Long QT (LQT)

Patients with LQT have higher risk of SCA as a result of torsades de pointes and VF. This condition might be as a result of congenital substrate such as in LQT syndrome (LQTS), or may be acquired.

1. Congenital LQTS

The long QT syndromes are phenotypically and genotypically diverse, but have in common the appearance of long Q–T intervals in the electrocardiogram (ECG), an atypical polymorphic VT known as torsades de pointes (TdP), and, in many but not all cases, a relatively high risk for sudden cardiac death.

The prevalence of this disorder is estimated at 1-2:10,000. Congenital LQTS is subdivided into eight genotypes distinguished by more than 400 mutations in at least seven different ion genes and a structural anchoring protein located on seven chromosomes (Table 25-1).^16,⁵⁹^–⁶³ All of these genotypes have a similar phenotypic presentation (long QT) but different clinical profiles regarding T wave patterns (Fig. 25-4), arrhythmia triggers (Fig. 25-5), prognosis, and response to therapy.⁶³^–⁶⁶ The phenotype penetration and expression is variable even in the same mutation.⁶⁷ The most common subgroups are LQT1, LQT2, and LQT3; they account for more than 90% of all genotyped LQTS patients.

a. LQT1:

It is the most common (40% to 50%) and least serious life-threatening genotype.^63,⁶⁶ The ECG pattern shows a long QT with a broad-based T wave (see Fig. 25-4). The trigger for cardiac arrhythmia is sympathetic hyperactivity associated with exercise (especially swimming) or emotions (see Fig. 25-5). Catecholamine increases the function of the slowly activating delayed-rectifier potassium channel (IKs) to shorten the Q–T interval during tachycardia. However, due to “loss-of-function” of the IKs channel in LQT1, the Q–T interval is prolonged and causes TdP, leading to SCD. Two patterns of inheritance have been identified:

(1) Jervell and Lang-Nielsen syndrome.⁶⁸ It is an autosomal recessive disease associated with deafness. Caused by more than 150 mutations in two genes that encode for the IKs channel (KCNQ1 and KCNE1), which affect the cardiac cell membrane and the production of the endolymph in the inner ear.⁶⁹

(2) Romano-Ward syndrome.^70,⁷¹ It is an autosomal dominant disease, more common, not associated with deafness, and broader (includes all other LQTS).

b. LQT2:

LQT2 is the second most common (35% to 50%) and second least serious life-threatening genotype.^63,⁶⁶ The ECG pattern shows long QT with a bifid, notched, low amplitude T wave (see Fig. 25-4). The triggers for cardiac arrhythmia are acute arousal with auditory stimuli or emotions, or during sleep or rest (see Fig. 25-5). It results from mutations in two genes (KCNH2 “HERG,” and KCNE2 “MiRP1”), causing “loss-of-function” of the rapidly activating delayed-rectifier potassium channel (IKr), and leading to Q–T prolongation, then to TdP and SCD.

c. LQT3:

It accounts for 10% of LQTS and manifests with a late-onset peaked or biphasic T wave pattern on the ECG.^62,^63,⁶⁵ Triggers for cardiac arrhythmia are rest or sleep. There are more than 50 SCN5A mutations that cause LQT3. The SCN5A-encoded defect causes “gain-of-function,” leading to production of persistent, noninactivating inward sodium current (INa) during the plateau phase of the action potential and prolongation of the Q–T interval.⁶⁹

d. LQT4:

It is a rare subgroup that manifests with moderate Q–T prolongation, severe sinus bradycardia, and episodes of atrial fibrillation.^72,⁷³ Usually exercise induces polymorphic ventricular arrhythmia, syncope, or SCD. The responsible gene is AnkirynB2 encoding the ankyrin B protein, which participates in the anchoring of several ion channels (Na+/K+ ATPase, Na+/Ca+ exchanger) and proteins (InsP3 receptor) to the cell membrane.^72,⁷³

e. LQT5:

It accounts for 2% to 3% of LQTS (rare), and results from the KCNE1 (minK) gene mutation, causing “loss-of-function” in the IKs channel. In homozygous or compound heterozygous form, it manifests as Jervell and Lange-Nielsen type II syndrome.⁷⁴

f. LQT6:

LQT6 is a very rare subgroup resulting from the KCNE2 (MiRP1) gene mutation, causing “loss-of-function” in the IKr channel.

g. LQT7:

It is another rare subgroup of LQTS, results from the KCNJ2 (Kir2.1) gene mutation causing “loss-of-function” in the Ik1 channel. It manifests as an Andersen-Tawil syndrome, which is characterized by potassium-sensitive periodic paralysis, neuromuscular manifestations, facial dysmorphic features, variable degree of Q–T interval prolongation with giant U waves, bidirectional, or polymorphic tachycardia, and, rarely, SCD.^75,⁷⁶

h. LQT8:

LQT8 is a rare subgroup type of LQTS called Timothy syndrome.⁷⁷ It is characterized by multiorgan dysfunction and results from a “gain-of-function” mutation in the CaCNA1C gene, which encodes the L-type calcium channel (CaV1.2). The manifestations include congenital heart disease, webbing (syndactyly) of the fingers and toes, immune deficiencies, autism, cognitive abnormalities, and severe Q–T prolongation with childhood sudden death.

i. Other LQT:

There are other LQTS to be discovered. Two new ones were reported recently, LQT9 (“gain-of-function” SCN4B gene mutation of INa) and LQT10 (“gain-of-function” CAV3 gene mutation of INa).

The risk of a second event (syncope or SCA) before age 18 is:⁶⁶

a. High (= 50%) in QTc = 500 ms with LQT1 and LQT2, or male sex in LQT3.

b. Intermediate (30% to 49%) in QTc = 500 ms with female sex LQT3, or QTc less than 500 ms in LQT3 or female sex LQT2.

c. Low (<30%) in QTc less than 500 ms in LQT1 or male sex LQT2.

Exercise should be restricted in all patients to prevent an event. The mechanism of LQTS is related to the amplification of transmural dispersion of repolarization (TDR) because of preferential prolongation of the action potential duration of M cells. The development of early after depolarization-induced triggered activity underlies the substrate and trigger for the development of life-threatening ventricular arrhythmias.⁵⁹

Recent studies have provided validation for reliance on the estimation of TDR index, measuring Tpeak-Tend interval and for the prediction of risk of SCD in patients with congenital or acquired long QT.^60,⁶¹

2. Acquired LQT:

Acquired Q–T prolongation is more commonly encountered in clinical practice than congenital long QT and may be associated with bradycardia or caused by hypokalemia, hypomagnesemia, hypothermia, or anorexia nervosa or may be a side effect from the use of class IA or III antiarrhythmic agents, or liquid protein diets. Bradycardia and delayed ventricular repolarization constitute the substrate for the development of polymorphic ventricular tachycardia that frequently degenerates into VF. SCA, in this group of patients, therefore, is usually iatrogenic, and the propensity to manifest Q–T prolongation after exposure to a trigger such as a drug may be related, in some patients, to an underlying genetic predisposition.

Table 25–1 Ion Channelopathy Disorders’ Characteristics

Figure 25-4 Three ECGs illustrating the typical Q–T morphology of the three most common long QT syndromes. Left, ECG of LQT1. Center, ECG of LQT2. Right, ECG of LQT3.

Figure 25-5 Gene-specific triggers for life-threatening arrhythmias in the three most common long QT (LQT) syndromes. Top, Exercise, emotion, sleep, or other triggers. Bottom, Swimming versus auditory stimulus.

(Adapted from Schwartz PJ, Priori SG, Spazzolini C, et al: Genotype-phenotype correlation in the long-QT syndrome: gene-specific triggers for life-threatening arrhythmias. Circulation 2001;103:89-95.)