Author
Jaime R. Antuna, MD
Resident Physician
Department of Emergency Medicine
University of California, San Francisco
Fresno, California
Disclosure: Jaime R. Antuna, MD, has disclosed no relevant financial relationships.
Editor
Catherine A. Lynch, MD
Clinical Instructor and Global Health Fellow
Attending Physician, Department of Emergency Medicine
Emory University School of Medicine, Emory Healthcare
Atlanta, Georgia
Disclosure: Catherine A. Lynch, MD, has disclosed no relevant financial relationships.
Reviewer
John A. McPherson, MD, FACC, FAHA
Director of Cardiovascular Intensive Care Unit
Associate Professor of Medicine
Division of Cardiovascular Medicine
Vanderbilt Heart and Vascular Institute
Nashville, Tennessee
Disclosure: John A. McPherson, MD, FACC, FAHA, has disclosed no relevant financial relationships.
An 18-year-old woman presents to the emergency department after experiencing a syncopal event 2 days ago. The patient had been hiking up a steep hill and then remembers waking up on the trail. She does not recall any chest pain, shortness of breath, palpitations, or dizziness prior to event. She denies recent dieting, use of over-the-counter or illicit drugs, and any past medical problems (except for a similar syncopal episode with exertion in the past). She reports that her younger brother had a similar episode of syncope in the past. On examination, the patient's vital signs are normal. She appears to be well and in no acute distress. Chest radiograph (shown) is normal.
An electrocardiogram (ECG) is obtained (shown). Head and neck exam is unremarkable. Cardiac exam is normal without rubs, murmurs, or gallops. There is no jugular venous distention; lungs are clear bilaterally. The patient's abdomen is soft and she has no peripheral edema. Neurologic exam is normal. Complete blood count, chemistry panel, pregnancy test, toxicology screen, and chest radiograph are normal. Image courtesy of ECG Wave-Maven.
Based on the ECG, what is the diagnosis?
A. Brugada syndrome
B. Long QT syndrome
C. Wolff-Parkinson-White syndrome
D. Mobitz type II
Answer: B. Long QT syndrome (LQTS)
LQTS is a disorder characterized by a prolongation of the QT interval on ECG and a propensity to ventricular tachyarrhythmia.[1] The ECG (shown) demonstrates prolongation of the QT segment with a QT interval of 0.6 s. LQTS can either be inherited or acquired. Congenital LQTS is suggested for this patient based on presentation and familial history of similar episodes. Image courtesy of ECG Wave-Maven.
What is the upper limit of normal for a QT interval in females?
A. 420 ms
B. 440 ms
C. 460 ms
D. 480 ms
Answer: C. 460 ms
Any value greater than 440 ms in males and 460 ms in females is considered to be prolonged. Because of the variability of the R–R segment in relation to a number of factors (e.g., age, heart rate, conditioning), the duration of the QT interval requires correction. This graph shows the upper limit of normal QT interval corrected for heart rate using three formulas: Bazett formula, Fridericia formula, and subtracting 0.02 s from QT for every 10 bpm increase in heart rate. The Bazett formula is most commonly used to obtain the corrected QT interval (QTc). Image courtesy of Wikimedia Commons.
This ECG revealed a QT interval of 480 ms and QTc interval of 600 ms. LQTS is diagnosed more frequently in women (70% of cases). The prevalence of congenital LQTS is thought to be 1 per 10,000 individuals, but it is likely underdiagnosed given the large number of disease carriers with a baseline normal QTc duration. Approximately 4,000 deaths per year are attributed to LQTS, including 30% of first-time cardiac events in patients with congenital LQTS. The risk of sudden death highlights the importance of early detection. Image courtesy of Cetin et al.[2]
At least 10 genes have been associated with LQTS (shown). Mutations in the genes responsible for potassium, sodium, and calcium channels in cardiac muscle have been implicated in congenital LQTS. Congenital forms of LQTS include Romano-Ward, Jervell-Lange-Nielsen, Andersen, and Timothy syndromes.
Which syndrome is associated with hearing loss?
A. Romano-Ward syndrome
B. Jervell-Lange-Nielsen syndrome
C. Andersen syndrome
D. Timothy syndrome
Answer: B. Jervell-Lange-Nielsen syndrome
This ECG is from a 5-year-old patient with congenital deafness and LQTS. Jervell-Lange-Nielsen syndrome is a congenital cause of LQTS that involves sensorineural hearing loss in the inner ear along with QT prolongation. This variant is inherited in an autosomal recessive pattern and is much less common than Romano-Ward syndrome. Romano-Ward syndrome exhibits autosomal dominant inheritance and includes LQT types 1-6, with subtypes 1-3 accounting for over 97% of cases. Patients typically experience symptoms during exertion and emotionally stressful periods (LQT1 and 2) or while asleep (LQT3). Image courtesy of Crotti et al.[3]
Andersen and Timothy syndromes are rare causes of congenital LQTS with characteristic physical exam findings. Andersen syndrome is associated with skeletal abnormalities such as scoliosis (shown), whereas Timothy syndrome is associated with congenital heart defects and musculoskeletal disorders. It is important to note that a significant number of mutations causing LQTS do not have 100% penetrance and result in carriers with normal QTc. Patients with normal QTc and LQTS mutations are acutely sensitive to drugs and electrolyte abnormalities that are associated with acquired causes of LQTS. These include hypokalemia, hypomagnesemia, hypocalcemia, and a number of commonly used medications.
A thorough medication history can help to identify possible acquired causes of LQTS. A list of QT-prolonging medications is shown.[4] Presenting complaints for LQTS include palpitations, dizziness, syncope, arrhythmias, and cardiac arrest. Unfortunately, there are no physical exam findings that would lead to the diagnosis of LQTS in the majority of patients. A history of inciting events may indicate the diagnosis. Exertion and emotional stress are known triggers. Patients should be asked about hearing loss, which is seen in some patients with congenital LQTS. Electrolytes should be assessed because this is a correctable cause of acquired LQTS.
Initially, the evaluation should be directed at identifying the underlying cause of the cardiac event. ECG helps to rule out other disease processes including Wolff-Parkinson-White syndrome (shown), Brugada syndrome, atrioventricular blocks, cardiac ischemia, and other arrhythmias. Note that some patients with LQTS may actually present with a normal QTc on initial ECG and require further evaluation. Echocardiography may help to rule out congenital heart defects and hypertrophic cardiomyopathy. Once LQTS is diagnosed, the patient should undergo genetic testing for known LQTS mutations. Image courtesy of Wikipedia Commons.
In patients whom LQTS is suspected, a diagnostic scoring tool using criteria developed by Schwartz (shown) can be helpful in determining the likelihood of LQTS. A score is given based on ECG findings as well as family and clinical history. A score of 4 or more is associated with a high probability of LQTS.[5]
Defects in ion channels predispose patients to episodes of torsade de pointes (TdP), which can cause cardiac arrest. TdP is a form of polymorphic ventricular tachycardia that results in a characteristic twisting of the QRS complex around the isoelectric baseline. This arrhythmia is associated with LQTS and can degenerate into more unstable rhythms. In the case of acquired LQTS, a pause usually precedes the onset of TdP. This form of TdP is said to be “pause dependent” (arrows). Image courtesy of ECG Wave-Maven.
In congenital LQTS, TdP is usually a result of increased catecholamine levels that lead to QT prolongation and is considered “adrenergic dependent,” with no pause prior to onset of rhythm (arrow).[6] Initial management of TdP is focused on stabilizing the patient and termination of the rhythm. Long-term management focuses on prevention of reoccurrence.
What is the first-line treatment in a stable patient with TdP?
A. Amiodarone
B. Magnesium
C. Synchronized cardioversion
D. Defibrillation
Answer: B. Magnesium
Initial treatment of TdP depends on the condition of the patient. If stable, magnesium (2-4 g IV) can be given in an attempt to correct the rhythm. Overdrive pacing may aid in terminating TdP if magnesium fails. TdP tends to be self-limited, so synchronized cardioversion is used as a last resort. QT-prolonging medications should be stopped and the patient’s electrolytes should be corrected to prevent reoccurrence. This ECG shows sinus rhythm (with multiple ventricular premature beats) spontaneously converting to TdP ventricular tachycardia, initiating a sequence of chest compressions and (later) defibrillation. Image courtesy of Nakstad et al.[7]
Long-term management is based on the underlying etiology. For congenital LQTS, beta blockers (continued indefinitely) are the treatment of choice. For acquired LQTS, the offending agent should be stopped and underlying electrolyte disorders corrected. In all cases, QT-prolonging medications should be avoided. For high-risk patients (i.e., QTc >500 ms, cardiac arrest, recurrent cardiac events despite medical therapy, family history of sudden cardiac death, LQT2 or LQT3 mutation), an implantable cardioverter defibrillator (shown) is recommended. If further events occur, a left thoracic sympathectomy may be necessary to decrease adrenergic-dependent arrhythmias. Image courtesy of Kansara et al.[8]
This patient was ultimately admitted to an inpatient telemetry unit and evaluated by cardiology. Congenital LQTS was suspected and the patient was started on beta blockers. Because exercise can precipitate arrhythmias in congenital LQTS, the patient was advised to avoid all contact sports. Her primary care provider and an outpatient cardiologist will follow up to assess her response to medical therapy. Other members of her family, particularly her brother, were encouraged to undergo screening for LQTS. The ECGs from her normal family member (top), heterozygous mutation carrier (middle), and homozygous mutation carrier (bottom) are shown. Image courtesy of Zhang et al.[9]
Author
Jaime R. Antuna, MD
Resident Physician
Department of Emergency Medicine
University of California, San Francisco
Fresno, California
Disclosure: Jaime R. Antuna, MD, has disclosed no relevant financial relationships.
Editor
Catherine A. Lynch, MD
Clinical Instructor and Global Health Fellow
Attending Physician, Department of Emergency Medicine
Emory University School of Medicine, Emory Healthcare
Atlanta, Georgia
Disclosure: Catherine A. Lynch, MD, has disclosed no relevant financial relationships.
Reviewer
John A. McPherson, MD, FACC, FAHA
Director of Cardiovascular Intensive Care Unit
Associate Professor of Medicine
Division of Cardiovascular Medicine
Vanderbilt Heart and Vascular Institute
Nashville, Tennessee
Disclosure: John A. McPherson, MD, FACC, FAHA, has disclosed no relevant financial relationships.
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