Clarence Khoo, MD, FRCPC, Shubhayan Sanatani, MD, FRCPC, Laura Arbour, MD, FRCPC, Andrew Krahn, MD, FRCPC
A 40-year-old man of Asian descent is being assessed following an aborted sudden cardiac arrest. His wife had found him with agonal respirations while sleeping and was unable to wake him. Upon arrival of the paramedics, his initial rhythm was determined to be ventricular fibrillation (VF), and he was successfully defibrillated with a single DC shock by an external defibrillator. His initial 12-lead ECG showed down-sloping ST-elevation in the inferior and lateral leads (Figure 50-1), and he thus proceeded to coronary angiography. This did not demonstrate any flow-limiting coronary artery stenosis. Echocardiography showed normal biventricular systolic function.
FIGURE 50-1 Twelve-lead electrocardiogram obtained from the patient following resuscitation of aborted sudden cardiac death. Notable findings include down-sloping J-point elevation of 0.1 mV in the inferior and lateral leads. There is also marked associated notching of the QRS in the affected leads. While the QT is prolonged, the QTc corrected for bradycardia is normal at 445 ms.
• Prior to the evaluation of any episode of sudden cardiac death (SCD), prompt resuscitation and the stabilization of any electrical or hemodynamic instability is imperative. If the patient is unable to follow commands following return of spontaneous circulation, or a substantial period of cerebral hypoxia is suspected, then therapeutic hypothermic cooling should be considered.
• The initial evaluation of SCD should include:
A thorough history collected from the patient, first responders, witnesses, and family members regarding preexisting cardiovascular disease, cardiac symptoms, previous syncopal events, medications (both prescription and over-the-counter), and a family history of SCD. Included in the latter should be a screen for suspicious deaths in the family, that is, epilepsy, drownings, single motor vehicle accidents, and sudden infant death syndrome (SIDS).
A 12-lead ECG and rhythm strip to assess for any evidence of ischemia, ongoing arrhythmia, or suggestive findings of a cardiomyopathy or ion channelopathy.
In adults, coronary angiography to rule out an acute coronary syndrome as the cause of SCD. Computed tomography in younger patients may be considered.
Echocardiography to assess for any structural cardiac abnormalities.
• In the event that a diagnosis is not evident after this preliminary screen, the following potential etiologies for a ventricular tachyarrhythmia must be entertained:
Primary electrical causes/inherited ion channelopathies: Long QT syndrome (LQTS), short QT syndrome (SQTS), Brugada syndrome (BrS), catecholaminergic polymorphic ventricular tachycardia syndrome (CPVT).
Subclinical structural disease: Coronary vasospasm, anomalous coronary arteries and cardiomyopathies including arrhythmogenic right ventricular cardiomyopathy (ARVC), hypertrophic cardiomyopathy (HCM), noncompaction, infiltrative cardiomyopathies.
• Further evaluation may include:
Consultation with a center with expertise in nonischemic sudden death conditions.
Exercise ECG testing to assess for failure of the QT interval to shorten with exercise (LQTS) or initiation of polymorphic or bidirectional ventricular tachycardia (CPVT).
Modified ECG with V1 and V2 leads placed 1 or 2 interspaces higher to improve the sensitivity of detecting a Brugada pattern.
Signal-averaged ECG (SAECG), which has utility in diagnosing ARVC.
Cardiac MRI (with contrast) to assess for cardiomyopathies with subtle structural abnormalities.
Pharmacologic challenge: Epinephrine infusion may make latent LQTS and CPVT apparent; procainamide infusion can unmask a Brugada pattern.
Genetic testing: If an inherited ion channelopathy or cardiomyopathy (eg, ARVC) is suspected, then genetic testing may reveal a mutation associated with the condition. A negative result does not exclude any of these conditions; the finding of a gene mutation of uncertain significance is much less helpful both diagnostically and with regards to screening of family members (see Chapter 51, Genetic Testing for Assessment of Inherited Arrhythmias).
DIAGNOSIS AND MANAGEMENT
• The patient demonstrated excellent neurologic recovery once extubated, and a comprehensive history was obtained from him with corroborative details from family members.
He had no previous history of cardiac diagnoses or symptoms.
There is no family history of unexplained syncope or cardiac arrest.
• A comprehensive diagnostic evaluation was performed in order to elucidate the etiology of the patient’s aborted sudden cardiac arrest:
Exercise treadmill test: The patient exercised to 10.4 METS (9 minutes) with no inducible arrhythmias and no abnormal prolongation of the corrected QT interval (QTc) at peak exercise or recovery.
ECG with elevated precordial leads: no evidence of a Brugada pattern.
Cardiac MRI: No structural abnormalities or myocardial scar visualized.
Drug infusion challenge: Epinephrine and procainamide infusion did not reveal any ECG evidence of LQTS or BrS.
Due to the otherwise negative work-up, and the finding of J-point elevation in the inferolateral leads shortly after his cardiac arrest, a potential diagnosis of SCD associated with an early repolarization pattern (ERP) was entertained. An implantable cardioverter defibrillator (ICD) was implanted for secondary prevention purposes.
EVALUATION OF UNEXPLAINED SUDDEN CARDIAC DEATH
• In the absence of structural heart disease, SCD may be the result of a primary electrical disorder, subclinical structural cardiac disease, or idiopathic VF (Table 50-1). With rigorous screening, approximately 50% of cases will have an identifiable cause.1
TABLE 50-1 Causes of Unexplained Sudden Cardiac Death
1. Idiopathic ventricular fibrillation (44%)
2. Primary electrical disorder/inherited channelopathy (39%)
a. Long QT syndrome (13%)
b. Catecholaminergic polymorphic VT syndrome (13%)
c. Early repolarization (8%)
d. Brugada syndrome (5%)
3. Subclinical structural cardiac disease (17%)
a. Arrhythmogenic right ventricular cardiomyopathy (10%)
b. Coronary spasm (6%)
c. Myocarditis (1%)
Data from Krahn AD, Healey JS, Chauhan V, et al. Systematic assessment of patients with unexplained cardiac arrest: Cardiac Arrest Survivors With Preserved Ejection Fraction Registry (CASPER). Circulation 2009;July28;120(4):278-285.
• While implantation of an ICD for secondary prevention purposes is warranted for most survivors of SCD with adequate neurologic recovery, identifying a cause for SCD may allow for the addition of pharmacologic therapy and appropriate lifestyle modification for patients. Identification of a genetic cause for SCD may also be of significant value in the screening of family members.
• A step-wise evaluation strategy involving electrocardiography, imaging modalities, provocative testing, and genetic screening should be employed (Figure 50-2).1
FIGURE 50-2 Suggested step-wise evaluation strategy for patients with unexplained sudden cardiac death. Abbreviations: ECG, electrocardiogram; EP, electrophysiology; MRI, magnetic resonance imaging. Adapted with permission from Krahn AD, Healey JS, Chauhan V, et al. Systematic assessment of patients with unexplained cardiac arrest: Cardiac Arrest Survivors With Preserved Ejection Fraction Registry (CASPER). Circulation 2009;July 28;120(4):278-285.
• LQTS may be suspected if prolongation of the QTc is seen on the resting ECG, or during exercise testing at peak exercise or early in recovery (Figure 50-3).
FIGURE 50-3 Representative 12-lead electrocardiogram from a patient with long QT syndrome obtained following an aborted cardiac arrest. The corrected QT (QTc) is prolonged at 530 ms with biphasic T waves in V1.
• Automated computer-derived QTc measurements should be verified with manual measurements using the following standardized method (Figure 50-4)2:
FIGURE 50-4 Standardized method of assessing the QT interval. In either lead II or V5, the tangent from the steepest portion of the down-sloping portion of the T wave is taken to the baseline to mark the end of the T wave. The measured QT is then corrected by the preceding RR interval as per Bazett formula.
1. Measurements should be obtained in either lead II or V5.
2. The intersection of the tangent of the steepest slope of the last portion of the T wave to the baseline defines the end of the T wave.
3. Corrected QT (QTc) is calculated by the Bazett formula (QTc = QT/√RR).
• ECG changes diagnostic for BrS are often transient and require either serial ECGs or provocative testing to unmask a type I Brugada pattern (2 mm ST elevation in V1 and V2 with an inverted T wave). Shifting the V1 and V2 ECG leads up 1 or 2 interspaces may suffice3; alternatively, a procainamide infusion can be used (Figure 50-5).
FIGURE 50-5 Anterior precordial leads (V1-V3) obtained from a patient with diagnosed Brugada syndrome and prior aborted sudden cardiac death. (A) Standard precordial lead placement with nonspecific J-point elevation in V1-V3. (B) Tracings from identical patient taken 1 minute later with V1 and V2 each moved up one interspace. Note the dramatic alteration in ST morphology that is now consistent with type I Brugada syndrome.
• CPVT should be suspected with the reproducible development of polymorphic ventricular extrasystoles or bidirectional VT with exercise (Figure 50-6).
FIGURE 50-6 Representative rhythm strip during an exercise treadmill test in a patient later diagnosed with catecholaminergic polymorphic ventricular tachycardia syndrome. Runs of polymorphic ventricular ectopy are seen here at peak exercise and are diagnostic for this condition.
• The diagnosis of ARVC requires multiple testing modalities that satisfy the ARVC task force criteria.4 Dilatation of the right ventricle on imaging ± regional wall motion abnormalities (Figure 50-7), an abnormal SAECG, or the finding of epsilon waves and extensive T-wave inversion in the anterior precordial leads (Figure 50-8) all contribute to the diagnosis.
FIGURE 50-7 Multimodality imaging studies performed in a patient with diagnosed arrhythmogenic right ventricular cardiomyopathy. (A) Echocardiographic apical four-chamber view demonstrating dilatation of the right ventricle at end-diastole. (B) Magnetic resonance imaging in the same patient revealing an aneurysmal segment of the basal right ventricle during systole (arrowheads).
FIGURE 50-8 Selected precordial leads obtained from a patient with diagnosed arrhythmogenic right ventricular cardiomyopathy. Both epsilon waves (arrowheads) and diffuse T-wave inversions up to V4 are present and qualify as major diagnostic criteria for this condition.
• ERP can be identified by the finding of J-point elevation of ≥1.0 mV in association with QRS slurring or notching in two contiguous leads, excluding V1 to V3.5
EARLY REPOLARIZATION PATTERN AND SUDDEN CARDIAC DEATH
• Inferolateral J-point elevation of ≥0.1 mV has been identified in 14% to 41% of individuals without an etiology for SCD after rigorous diagnostic testing.6
• At present, the causality of ERP and SCD remains unclear, but there is a clear association between the two. This likely represents an imbalance of early currents INa and Ito. Some investigators believe that a channelopathy related to BrS may be responsible, while others believe that ERP may identify individuals more prone to developing fatal arrhythmias in the presence of various triggers.7
• ERP is common in the general population and in the majority of cases is a benign finding. Individuals at higher risk for SCD may include6,8:
J-point elevation ≥0.2 mV.
Distribution in multiple leads, especially if inferior leads involved.
Presence of QRS notching.
Dynamic fluctuation of J-point amplitude.
Horizontal or down-sloping ST segments.
Persistent J-point elevation with exercise.
• Secondary prevention patients should be offered an ICD unless contraindications exist. No validated risk stratification strategy exists for primary prevention patients with ERP, and thus the appropriate management of these individuals remains largely uncertain.
• Recurrence of VF in patients with ERP may be reduced with infusion of isoproterenol or oral quinidine.5
1. Krahn AD, Healey JS, Chauhan V, et al. Systematic assessment of patients with unexplained cardiac arrest: Cardiac Arrest Survivors With Preserved Ejection Fraction Registry (CASPER). Circulation. 2009;120(4):278-285.
2. Postema PG, De Jong JS, Van der Bilt IA, et al. Accurate electrocardiographic assessment of the QT interval: teach the tangent. Heart Rhythm. 2008;5(7):1015-1018.
3. Sangwatanaroj S, Prechawat S, Sunsaneewitayakul B, et al. New electrocardiographic leads and the procainamide test for the detection of the Brugada sign in sudden unexplained death syndrome survivors and their relatives. Eur Heart J. 2001;22(24):2290-2296.
4. Marcus FI, McKenna WJ, Sherrill D, et al. Diagnosis of arrhythmogenic right ventricular cardiomyopathy/dysplasia: proposed modification of the task force criteria. Circulation. 2010;121(13):1533-1541.
5. Stern S. Clinical aspects of the early repolarization syndrome: a 2011 update. Ann Noninvasive Electrocardiol. 2011;16(2):192-195.
6. Derval N, Simpson CS, Birnie DH, et al. Prevalence and characteristics of early repolarization in the CASPER registry: cardiac arrest survivors with preserved ejection fraction registry. J Am Coll Cardiol. 2011;58(7):722-728.
7. Benito B, Guasch E, Rivard L, et al. Clinical and mechanistic issues in early repolarization of normal variants and lethal arrhythmia syndromes. J Am Coll Cardiol. 2010;56(15):1177-1186.
8. Bastiaenen R, Raju H, Sharma S, et al. Characterization of early repolarization during ajmaline provocation and exercise tolerance testing. Heart Rhythm. 2013;10(2):247-254.