Pearls From Clinical Cases

December 31, 2006

A 20-year-old woman has had several episodes of syncope since she enteredcollege 2 months earlier. Although 1 or 2 episodes were associated with exercise,most were not. All occurred at times of surprise and/or emotional stress:she fainted twice when the bell rang at the end of a test, once after her alarmclock suddenly awakened her in the morning, and once when she received adisturbing phone call from home.

Case 1:

Young Woman With RecentEpisodes of Syncope

A 20-year-old woman has had several episodes of syncope since she enteredcollege 2 months earlier. Although 1 or 2 episodes were associated with exercise,most were not. All occurred at times of surprise and/or emotional stress:she fainted twice when the bell rang at the end of a test, once after her alarmclock suddenly awakened her in the morning, and once when she received adisturbing phone call from home.

HISTORY

When the patient was a teenager, she had sporadic fainting episodes butat a much lower frequency than recently. None of these episodes-nor thoseof the past 2 months-were accompanied by neurologic symptoms (eg, weaknessor tingling) or cardiac symptoms (eg, chest discomfort or dyspnea). Sheis otherwise healthy; her only medication is an oral contraceptive. Her mother,father, and 14-year-old sister are healthy as well. She has no family history ofserious heart disease.

PHYSICAL EXAMINATION

This young woman is of normal weight. Heart rate is 68 beats per minute,and no murmurs or clicks are heard. Results of a neurologic examination-aswell as the other physical findings-are normal.

LABORATORY AND IMAGING RESULTS

Hemogram, chemistry panel results, and thyroid function are all normal.The ECG shows normal sinus rhythm without delta waves. The PR interval is0.16 seconds and the QT interval is 0.46 seconds.

Which of the following is the most appropriate management strategy?

A.

Initiate amiodarone, 200 mg/d.

B.

Recommend cervical sympathectomy as soon as possible.

C.

Initiate metoprolol, 50 mg twice daily.

D.

Recommend insertion of a cardiac pacemaker as soon as possible.

Case 1:

CORRECT ANSWER: C

This patient has clinical findings typical of the

long QTinterval syndrome

(

LQTS

). This genetically transmitteddisorder of ventricular repolarization predisposes carriersto cardiac arrhythmias that can result in syncope or suddendeath.

Epidemiology.

The syndrome is typically seen inyoung persons; the incidence is higher in females. Theage at first cardiac event is 13 9 years for males and 20 14 years for females.

1

Pathophysiology.

LQTS can be caused by a variety ofmutations in either potassium-channel genes (eg, LQT1and LQT2) or sodium-channel genes (eg, LQT3). Theconsequent abnormalities result in prolongation of the QTinterval and an elevated risk of torsades de pointes, whichcan degenerate into cardiac arrest and sudden death.

2

The more common variants are caused by mutationsat LQT1 and LQT2; each has a relatively typical and distinctgene-specific clinical profile. In the majority of patientswith an LQT1 locus mutation, most cardiac eventsoccur during exercise, whereas in patients with an LQT2locus mutation, events are associated with the emotionsproduced by acute arousal-such as brisk awakening byan alarm clock or a sudden, unexpected loud noise.

3

The risk of mortality in LQTS is determined mainlyby genotype (it is higher in patients with LQT2 locus mutationsthan in those with LQT1 mutations) and by thelength of the QT interval (risk is proportional to the prolongationof the interval).

1

Diagnosis.

In patients with syncope, an ECG may show evidence of a long QT interval. If the patient has relativeswho have documented LQTS or who died suddenly,family studies are indicated. Include in these evaluationsan ECG and a detailed cardiac clinical history that focuseson syncope and associated events. A well-developed criteria/point system for the diagnosis of LQTS has been published.4 Detailed genotype analysis has elucidated thenature of LQTS but remains a specialized research techniquenot readily available. Here the patient is a youngwoman with clinical findings that strongly suggest LQT2locus mutation.

Therapy.

Recent studies suggest that therapy is indicatedfor all patients, regardless of the length of the QTinterval.

1

In addition, this patient's symptoms greatly interferewith her life; this constitutes another indication fortherapy.The current initial treatment of choice is β-blockade(choice C), which seems to work by attenuating theadrenergic-mediated trigger mechanisms involved inLQTS. Available data suggest that such therapy significantlyreduces rates of cardiac events and syncopalepisodes, although it does not provide absolute protectionagainst fatal events.

3

Amiodarone (choice A) is not appropriate and mayeven be dangerous. It prolongs the QT interval and, by inference,increases the risk of torsades de pointes and seriouscardiac events.

4

Cardiac pacemakers (choice D) havebeen used in patients with LQTS and sinus bradycardia,but they have also resulted in an increased incidence ofsudden death.

3

Before the discovery of β-blockers, cervicalsympathectomy (choice B) was used to diminishadrenergic surges, and this therapy is effective. However,it is now reserved for patients in whom LQTS cannot beadequately controlled with drugs.

3

A promising new option is the implantation of a cardioverterdefibrillator. According to anecdotal reports, thedevice has reduced the incidence of sudden death in patientswith LQTS who are already taking β-blockers.

Outcome of this case.

Metoprolol was prescribed,and the patient's condition improved. She was cautionedabout the use of instigating devices such as loud alarmclocks, doorbells, and phones. After 4 months of therapy,she has had only 1 episode of syncope, which occurredduring a nighttime fire drill in her dormitory.

References:

REFERENCES:

1.

Priori SG, Schwartz PJ, Napolitano C, et al. Risk stratification in the long-QT syndrome.

N Engl J Med.

2003;348:1866-1874.

2.

Vincent GM. The long-QT syndrome-bedside to bench to bedside.

N Engl JMed.

2003;348:1837-1838.

3.

Al-Khatib SM, LaPointe NM, Kramer JM, Califf RM. What clinicians shouldknow about the QT interval.

JAMA.

2003;289:2120-2127.

4.

Moss AJ. Long QT syndrome.

JAMA.

2003;289:2041-2044.