Acute Care

A 16-year-old girl was brought to the emergency department of a rural hospital shortly after a single- vehicle incident, in which the car was found resting on its roof. Emergency medical services (EMS) personnel reported that they arrived about 20 minutes after the accident and found the patient restrained but confused. She was dangling with her head down, held by the shoulder and lap belts. Although the patient denied any physical pain or injury, she was immobilized before being transported to the hospital, in accordance with the EMS protocol for pretransport immobilization of trauma victims.

In the emergency department, the patient said she had been in her usual state of good health up until the accident. She recalled leaning over to retrieve something from the floor of the car just before the accident, and then apparently she “passed out.” During the emergency department stay, the patient stated she experienced intermittent chest discomfort and shortness of breath. The patient denied any history of such symptoms, and the review of systems was otherwise unremarkable.

On further questioning the patient described an episode of hypoglycemia at age 10 years and an isolated seizure at age 14 years, with negative workups both times. The patient had been taking 60 mg/day of fluoxetine for the treatment of her depression since age 12 years. She denied any use of alcohol, tobacco products, and illicit or nonprescription drugs. Her family history was significant for several conditions. Her paternal great-grandmother died of unknown causes at age 33; her paternal grandmother died after a seizure at age 52; her aunt had a history of seizures, palpitations, and syncope; her grandfather committed suicide in his 40s; and her sister had a history of palpitations.

The physical examination was unremarkable; the patient was alert and oriented and had normal vital signs. A computed tomography (CT) scan of the head, cervical spine x-rays, complete blood cell count, comprehensive chemical panel, and amylase, lipase, and pregnancy tests were all normal. A chest x-ray showed some patchy bilateral upper-lobe air space disease, which was thought to be caused by her dependent position after the accident and appeared to be of no clinical significance.

The patient was placed in overnight observation. The troponin and myoglobin levels were normal through 7 hours after the accident. During the observation period, the patient reported 2 episodes of shortness of breath accompanied by chest pain, both of which were short-lived and resolved spontaneously. A repeat chest x-ray before discharge was normal.

Within hours of discharge to her home, the patient experienced severe palpitations and appeared to have what was described as a seizure, followed by apnea, which was witnessed by her parents. Her father (an emergency medical technician and firefighter) began rescue breathing, and within moments the patient began breathing on her own. EMS personnel found the patient in no distress and transported her back to the emergency department for further evaluation.

During this second visit, the patient again had a completely normal physical examination; her blood work and a repeat head CT were normal. Her electrocardiogram (ECG) showed a corrected QT (QTc) interval of 728 ms (the upper-normal limit for this patient would be approximately 470 ms) without any other abnormalities (Figure). This prolongation of the QT interval was unrecognized by the emergency department staff. While in the emergency department, the patient had another episode of palpitations. A rhythm strip revealed nonsustained torsades de pointes, which was also not recognized at that time, because the monitor system used did not sound an alarm. However, as a result of this second episode of apnea, syncope, and/or seizure, arrangements were made to have the patient transported to a tertiary children’s hospital. During the transport she had a third brief episode of syncope, which resolved spontaneously.

After arriving at the children’s hospital, the patient was reevaluated, found to have no immediate problems, and was about to be sent home when she had another episode of palpitations. At this time, the rhythm strip revealed ventricular tachycardia, and the patient was given a lidocaine bolus, which converted her to a normal sinus rhythm.

The patient was started on an intravenous lidocaine drip and admitted to the intensive care unit (ICU). After 3 days in the ICU, she was given a preliminary diagnosis of long QT syndrome and was prescribed the oral beta-blocker atenolol. After stabilization for a few more days, she was discharged.

Subsequent to discharge from the children’s hospital, the patient continued to have episodes of tachycardia and bradycardia and eventually consulted a cardiologist. The cardiologist, specializing in long QT syndrome, recommended placement of a dual-function unit device that combines an automatic implantable cardioverter defibrillator and a pacemaker. The patient was ultimately diagnosed with bradytachy syndrome with long QT syndrome and has been doing well since her operation.

Discussion
Long QT syndrome is an uncommon but very important etiology of syncope in otherwise apparently healthy children. It has been estimated that about 1 in 3000 people in the United States has this disorder.¹

The QT interval is a measurement that represents the total time from the beginning of ventricular depolarization through complete repolarization. Measurement of the QT interval begins at the start of the QRS complex and extends to the end of the T wave. Variations in the measurement occur as a function of heart rate, and as a result, a value called QTc—the corrected QT interval—is more typically used. The QTc is calculated as the QT interval divided by the square root of the RR interval, measured in seconds. QTc values above 0.44 seconds are generally considered abnormal and warrant further investigation. This is important because when some of the ventricular muscle takes a long time to repolarize, cardiac dysfunction and arrhythmias, such as torsades de pointes, can occur.² In general, the longer the QTc, the higher the risk of symptoms and/or sudden death.³

Causes
The etiology of long QT syndrome can be broken down into 2 categories: acquired (common) and congenital (uncommon). Acquired causes of long QT syndrome include different types of medications (Table 1) and predisposing electrolyte disturbances, including hypokalemia, hypocalcemia, and hypomagnesemia.^4,5 An excellent and exhaustive list of drugs that prolong the QT interval and/or induce torsades de pointes can be found online at www.torsades.org.

If acquired conditions have been ruled out, consider congenital causes for long QT interval syndrome, which are usually the result of mutations in genes controlling sodium or potassium channels. Approximately 200 mutations, at 7 gene sites, have been identified; 3 genetic loci account for nearly 98% of the genetic forms of the syndrome so far.^6-8 The earliest discovered congenital cause, which is known as the Jervell and Lange-Nielsen syndrome, is associated with deafness and is autosomal recessive. The next described entity, called Roman-Ward syndrome, is not associated with deafness and is autosomal dominant.^9,10

Clinical Presentations
Most patients who present to a physician with long QT syndrome do so after a syncopal episode, a suspected cardiac event, or a seizure. There are 3 typical presentations. The first involves ECG findings. As mentioned earlier, the ECG may show a QTc of more than 0.44 seconds (the small variance in this number is related to the age of the patient). Other ECG findings may include T- and/or U-wave abnormalities. Not all long QT interval patients demonstrate abnormalities on a routine 12-lead ECG, however.

Second, and most common, the patient may describe symptoms ranging from trivial dizziness to complete syncope and/or seizures. These symptoms often follow activities that require exertion or events related to emotional stress. Children in particular may present with a syncopal episode secondary to exercise, fright, or a sudden startle.¹¹

Finally, long QT syndrome may present as sudden cardiac death, and the diagnosis, therefore, may never be firmly established. Congenital cases of long QT interval syndrome have a high mortality rate; the annual mortality rate may approach 20% if untreated,¹² with a cumulative rate of 53% by year 15.¹³ Treated patients, however, have a 1% annual fatality rate.¹⁴

Diagnosis
Recognition of a prolonged QT interval in a patient with syncope is crucial, because this seemingly benign ECG finding may place the patient at risk for a potentially fatal ventricular arrhythmia, such as torsades de pointes.¹⁵ Once identified, additional workup is required. If suspected, Holter monitoring and treadmill testing may be beneficial for diagnosis.³

The ability to diagnose long QT syndrome depends on the clinical context, ECG findings, and the patient’s family history. Long QT syndrome must be considered in children or in young patients who present with unexplained syncope or seizures. Genetic testing may have prognostic value for family members. Carriers of mutation varieties who do not demonstrate prolonged QT intervals during electocardiographic screening may be detected by genetic screening.¹⁶ Electrophysiologic testing is not helpful for diagnosis.¹⁷ In borderline cases, exercise testing may aid in categorization, because a lengthening of the QT interval may be uncovered during the recovery phase.¹⁷ Many cardiologists use a standardized, graded point system to aid in the diagnosis (Table 2).

Management
Management includes discontinuing the possible offending medications, correcting electrolyte abnormalities, and monitoring the patient closely for response to therapeutic medications.

Recent discoveries of different subtypes of long QT syndrome indicate that genetic typing may be useful in determining treatment, because various subtypes may need different forms of treatment and/or counseling.^16,18

For patients with idiopathic long QT syndrome who do not have syncope, complex ventricular arrhythmias, or a family history of sudden cardiac death, typically no therapy is recommended. Treatment with beta-blockers at the maximum tolerable dose is the first-line therapy for patients with a positive family history of early sudden cardiac death or for asymptomatic patients who have complex ventricular arrhythmias.¹⁴

Patients with syncope may need additional medicines beyond beta-blockers. Such patients may require the addition of class IB antiarrhythmic drugs, such as lidocaine, tocainide (Tonocard), or mexiletine (Mexitil). If symptoms persist despite medical management, surgery may be indicated to interrupt the sympathetic stellate ganglion in the left side of the neck.¹⁴ Placement of internal cardiac defibrillators may be necessary for patients who continue to experience syncope despite these interventions.

Permanent cardiac pacing may be indicated to prevent tachybradycardia and/or pauses that can lead to a lethal rhythm, such as torsades de pointes.¹⁴ It is vital for patients with long QT syndrome to avoid drugs that can cause arrhythmias.

Conclusion
Patients with unexplained syncopal attacks or seizures should be evaluated for long QT interval syndrome. Patients with acquired cases should have their medication adjusted and/or their medical conditions treated. Patients with suspected congenital varieties need further screening of family members. The patient involved in this case has done well with beta-blocker therapy and an implanted pacemaker/defibrillator.

References
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2. Viskin S. Long QT syndromes and torsade de pointes. Lancet. 1999;354:1625-1633.

3. Garson A Jr, Dick M II, Fournier A, et al. The long QT syndrome in children. An international study of 287 patients. Circulation. 1993;87:1866-1872.

4. Maisel WH, Kuntz KM, Reimold SC, et al. Risk of initiating antiarrhythmic drug therapy for atrial fibrillation in patients admitted to a university hospital. Ann Intern Med. 1997;127:281-284.

5. Nash DT. Prolonged QT interval: causes, consequences, and prevention. Consultant. 2004;44:319.

6. Zareba W, Rosero S. Long QT syndrome. June 2005. Available at www.emedicine.com/med/topic1983.htm.

7. Priori SG, Napolitano C, Schwartz PJ, et al. Association of long QT syndrome loci and cardiac events among patients treated with beta-blockers. JAMA. 2004;292: 1341-1344.

8. Gordon RY, Nash IS. Middle-aged woman with chest pain and dyspnea. Consultant. 2004;44: 1163-1166.

9. Georgijevic ML. Molecular genetics in the hereditary form of long QT syndrome [in Croatian]. Med Pregl. 2000;53:51-54.

10. 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.

11. Ali RH, Zareba W, Moss AJ, et al. Clinical and genetic variables associated with acute arousal and nonarousal-related cardiac events among subjects with long QT syndrome. Am J Cardiol. 2000; 85:457-461.

12. Khan IA. Clinical and therapeutic aspects of congenital and acquired long QT syndrome. Am J Med. 2002;112:58-66.

13. Engelstein ED. Long QT syndrome: a preventable cause of sudden death in women. Curr Womens Health Rep. 2003;3:126-134.

14. Khan IA. Long QT syndrome: diagnosis and management. Am Heart J. 2002;143:7-14.

15. Rubin RN. Young woman with recent episodes of syncope. Consultant. 2004;44:132-135.

16. Napolitano C, Priori SG, Schwartz PJ, et al. Genetic testing in the long QT syndrome: development and validation of an efficient approach to genotyping in clinical practice. JAMA. 2005;294:2975-2980.

17. Moss AJ. Long QT syndrome. JAMA. 2003;289:2041-2044.

18. Kaufman ES. Efficient genotyping for congenital long QT syndrome. JAMA. 2005;294: 3027-3028.