Case Illustrations of Long QT Syndrome

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Abstract

Long QT syndrome (LQTS) is a rare potentially life-threatening condition. Physicians must remain vigilant and consider LQTS as a possible etiology in patients with a history of syncope. Prolongation of the QT interval on electrocardiogram (ECG) is an essential component for the diagnosis of LQTS, despite the limitations of this technique. Experience of analyzing the ECG and calculating corrected QTc still remain relevant and are the mainstay diagnostic tools. Often, the first sign of the problem is observed after careful evaluation of the resting ECG for the hallmark of the disorder. Unfortunately, more than 60% of physicians—even cardiologists—have been known to misinterpret the QT interval on ECG. The cases discussed in this article highlight the variable clinical presentation of prolonged QT interval and the need to be highly vigilant in clinical evaluation.

Citation
American Heart Hospital Journal 2010;8(1):58–62
DOI
https://doi.org/10.15420/ahhj.2010.8.1.58

The term ‘torsades de pointes,’ coined in 1966 to describe the peculiar appearance of a ventricular tachycardia occurring in an elderly woman with heart block, is often translated as a ‘twisting of the points,’ referring to the beat-to-beat changes in the QRS axis.1 Congenital syndromes involving QT-interval prolongation and syncope or sudden death were first described in the late 1950s and early 1960s.1–3 However, the congenital long QT syndrome (LQTS) is rare, while the acquired LQTS, particularly associated with use of various drugs, is common. The few electrocardiographically documented cases of syncope or sudden death in patients with a congenital LQTS have been characterized by torsades de pointes.4 Because of the malignant clinical features of LQTS and the need for a prompt diagnosis that leads to effective treatment, every physician should be aware of its varied clinical presentation and also be able to recognize LQTS on electrocardiogram (ECG). Often, the first sign of the problem is observed on careful evaluation of the resting ECG for the hallmark of the disorder. Unfortunately, more than 60% of physicians—even cardiologists—have been known to misinterpret the QT interval on ECG.5 In this article we present three cases of prolonged QT interval presented to National University Hospital, Singapore, with the aim of increasing awareness and knowledge about LQTS within the general medical community. These cases highlight the variable clinical presentation of prolonged QT interval and the need to be highly vigilant in clinical evaluation.

Clinical Cases

The first case is an octogenarian woman hospitalized for frequent falls due to syncope and knee pain under the orthopaedics team. She has a past medical history of hypertension and paroxysmal atrial fibrillation. Her medications include tramadol hydrochloride, hydrochlorthiazide, and aspirin. Clinical examination was otherwise unremarkable except for the clinical findings of osteoarthritis of the bilateral knee joints. Laboratory investigation showed hypokalemia (serum potassium 2.9mmol/l), which was attributed to hydrochlorthiazide. The electrocardiogram showed sinus rhythm and prolonged QTc of 592 milliseconds, but this abnormality went unrecognized by the attending physician (see Figure 1). The morning prior to her discharge she experienced sudden cardiovascular collapse. The cardiac rhythm showed ventricular fibrillation that was successfully defibrillated.

She was subsequently managed in the intensive care unit. Cardiac monitoring showed recurrent runs of polymorphic ventricular tachycardia demonstrating pause dependence that was typical of drug-induced prolongation of QT interval (see Figure 2). She continued to have recurrent runs of polymorphic ventricular tachycardia in spite of correction of hypokalemia and administration of intravenous magnesium. Episodes of polymorphic ventricular tachycardia stopped after temporary transvenous pacing, which kept the heart rate above 80 beats per minute (bpm). Hydrochlorthiazide was stopped and she was discharged from hospital with no subsequent recurrence of the problem.

The second case is a 25-year-old Chinese woman, a soldier, who was referred to a neurologist at National University Hospital for two episodes of clinical tonic clonic seizures. The first episode of witnessed seizure occurred when she was resting after a prolonged aqua training session in the swimming pool; the second episode of seizure occurred a few hours later when she was about to be examined by the attending medical officer. She did not have any family history of sudden cardiac death. The clinical examination was otherwise unremarkable. The neurologist’s clinical diagnosis was epilepsy and the patient was recommended carbamazepine. However, she was also referred to a cardiac electrophysiologist to exclude a cardiac cause for her seizure and syncope. Her electrocardiogram before initiation of carbamazepine showed a prolonged corrected QT interval of 613 milliseconds, with broad T-waves consistent with electrocardiogram of LQTS type 1 (LQT1) (see Figure 3). The Schwartz score of 56 was more in keeping with a high probability of congenital prolonged QT syndrome. The exercise treadmill test was abnormal. The patient was only able to achieve 80% of maximal heart rate at stage 4 of Bruce protocol. Baseline corrected QT interval before exercise was 481 milliseconds on treadmill electrocardiogram; however, corrected QT was prolonged during the immediate recovery phase at 571 milliseconds when the heart rate decelerated to 100bpm. In LQT1, syncope or sudden death is triggered by emotional or physical stress; diving and swimming are LQT1-specific triggers.7 QT-interval prolongation may be especially notable during or after exercise or epinephrine challenge.8 The patient was started on metoprolol and was advised against strenuous physical exercise and aquatic sports. Since then she has been well, with no recurrence of seizure.

The third case is a 29-year-old Malay woman who had been evaluated by many physicians for recurrent syncope over a number of years. She had a positive family history of sudden cardiac death (her sister died suddenly at less than 40 years of age; however, the cause of death was unknown). Her clinical examination was unremarkable. The ECG showed prolonged corrected QT interval suggestive of LQT1 (see Figure 4). She also had multiple runs of polymorphic ventricular tachycardia on telemetry monitoring. A diagnosis of LQTS1 was eventually made by us. In view of her high risk of sudden cardiac death, an automated implantable cardioverter–defibrillator (AICD) was implanted in addition to treatment with atenolol. She had two appropriate AICD shocks that occurred within six months of implantation due to polymorphic ventricular tachycardia. Screening of family members was also advised; however, none came forward.

Discussion

These cases highlight the inability of attending physicians to at least suspect long QT interval on ECG. Failure to recognize prolonged QT interval has been described before. Most physicians, including many cardiologists, cannot accurately calculate corrected QT interval or correctly identify prolonged QT interval. There are several reasons behind this, the main one being not considering that long QT may be present. The other reasons are compounding factors such as heart rate, presence of U-waves, and flattened T-waves.5

Drug-induced torsades de pointes is a significant cause of morbidity and mortality, and non-cardiac drugs have been implicated in an increasing number of cases. In the first case, it must be noted that the cause of recurrent falls due to syncope in the elderly can be mutifactorial.9 Often, the main etiology of this symptom remains elusive and difficult to diagnose.9 In this case, the cause of her syncope was possibly a torsades de pointes as a consequence of diuretic-induced hypokalemia. Many drugs can prolong the QTc interval. QT prolongation, however, is a surrogate marker with an imperfect predictive value for fatal cardiac arrhythmias and sudden cardiac death, and it is difficult to predict whether a drug will cause torsades de pointes. For the vast majority of drugs known to induce QTc prolongation, it has been demonstrated that the slowing of the action potential is a consequence of the blockage of the rapid component of the delayed rectifier potassium channel (Ikr) through blockade of the human ether a go-go related gene (HERG).

The extent to which blocking of this channel results in torsades de pointes or sudden cardiac death, however, is highly variable among subjects.10 Risk factors for drug-induced torsades de pointes are female sex, hypokalemia, bradycardia, recent conversion of atrial fibrillation especially with QT-prolongation drug, congestive heart failure, baseline QT prolongation, subclinical LQTS, and ion-channel polymorphisms.11 Torsades de pointes often occurs with underlying hypokalemia and bradycardia, as in the first case. Treatment of drug-induced acquired LQTS complicated by torsades de pointes is aimed at increasing heart rate and preventing pause-dependent initiation of polymorphic ventricular tachycardia. Therapies include isoproterenol, pacing, and magnesium infusion. Intravenous potassium infusion to maintain serum potassium at the upper limit of the physiologic range is another strategy for the treatment of drug-induced torsades de pointes.

The second and third cases were eventually diagnosed as congenital LQTS, but not at first presentation. Nearly 25% of patients seen in epilepsy clinics and monitoring units do not have epilepsy.12,13 It is important for physicians to recognize these transient non-epileptic events that may resemble seizures in order to avoid unnecessary treatment with antiepileptic drugs, which itself may be proarrhythmic.14 In the second case the epilepsy was misdiagnosed and the eventual administration of carbamazepine would have further prolonged the QT interval, thereby increasing the patient’s risk of developing torsades de pointes.14

LQT1 is the most common form of this syndrome. The criteria for diagnosis usually include evaluation of the specific clinical setting and assessment of the ECG features. The Schwartz score, a weighted scoring system incorporating the measured resting QTc interval and other clinical and historical factors, has been used to diagnose LQTS.6 The probability of having LQTS is rated as low, intermediate, or high for scores of <1, 2–3, and 4, respectively. Also, abnormalities in T-wave amplitude and duration can help to distinguish among LQT1, LQT2, and LQT3. The LQT1 group usually has a broad and pronounced T-wave or late onset of a normal-appearing T-wave.

The prevalence of congenital LQTS is around 1:2,000 to 1:5,000 LQTS. If untreated, there is 20% mortality in the first year in the presence of syncope and about 50% in the next 10 years; therefore, physicians should be alert and pay careful attention to clinical and electrocardiographic features of the disease. An accurate measurement of the QT interval is valuable in the diagnosis of LQTS, as highlighted in the cases discussed above.

The QT interval should be determined as a mean value derived from at least three to five cardiac cycles, and is measured from the beginning of the earliest onset of QRS complex to the end of the T-wave. The QT measurement should be made in lead II and lead V5 or V6, with the longest value being used. The QT interval is usually corrected for heart rate using the Bazett formula.15

When a prolonged QTc is identified after a syncopal event in the absence of acquired causes of QT prolongation, a diagnosis of LQTS can be made, and ECGs should be obtained on all first-degree family members to determine whether others are affected. Unexplained sudden death should trigger a similar evaluation to determine whether LQTS is present in the family. Rarely, an asymptomatic individual is identified with LQTS by QTc prolongation on ECG obtained for another reason. A detailed family history of syncopal events and sudden cardiac death not only in first-degree relatives but also in more remote relatives is important. For cases where the diagnosis is not clear, a clinical scoring system based on personal and family history, symptomatology, and ECG has been developed by Schwartz et al.6 Additional methods of testing include Holter and exercise testing. Exercise testing has been shown to be useful in the diagnosis of LQTS in asymptomatic patients with borderline or normal QT interval. Measurement of an exaggerated QTc interval prolongation during the recovery from exercise testing is considered to be useful in the clinical diagnosis of prolonged QTc.16,17 Genetic testing has so far largely been used for research purposes, making the phenotypic assessment the mainstay in the diagnosis of this genetic disorder.

Conclusion

Prolonged QT syndrome is a rare condition with variable clinical presentation. Physicians need to be highly vigilant and consider LQTS in the clinical evaluation of syncope. Prolongation of the QT interval on ECG is an essential component for the diagnosis of LQTS, despite its limitations. Experience of analyzing the ECG and calculating corrected QTc still remains relevant despite advances in medical technology. The cases discussed in this article highlight the tendency of physicians to miss the diagnosis of prolonged QT, which can have fatal consequences.

References
  1. Dessertenne F, La tachycardie ventriculaire à deux foyers opposés variables, Arch Mal Coeur, 1966;59:263–72.
  2. Jervell A, Lange-Nielsen F, Congenital deaf-mutism, functional heart disease with prolongation of the Q-T interval, and sudden death, Am Heart J, 1957;54:59–68.
  3. Ward OC, A new familial cardiac syndrome in children, J Ir Med Assoc, 1964;54:103–6.
  4. Viskin S, Fish R, Zeltser D, et al., Arrhythmias in the congenital long QT syndrome: how often is torsade de pointes pause dependent?, Heart, 2000;83:661–6.
  5. Viskin S, Rosovski U, Sands AJ, et al., Inaccurate electrocardiographic interpretation of long QT: the majority of physicians cannot recognize a long QT when they see one, Heart Rhythm, 2005;2:569–74.
  6. Schwartz PJ, Moss AJ, Vincent GM, Crampton RS, Diagnostic criteria for the long QT syndrome: an update, Circulation, 1993;88:782–4.
  7. Schwartz PJ, Priori SG, Spazzolini C, et al., Genotype-phenotype correlation in the long-QT syndrome: gene-specific triggers for lifethreatening arrhythmias, Circulation, 2001;103:89–95.
  8. Vyas H, Hejlik J, Ackerman MJ, Epinephrine QT stress testing in the evaluation of congenital long-QT syndrome: diagnostic accuracy of the paradoxical QT response, Circulation, 2006;113:1385–92.
  9. Brignole M, Alboni P, Benditt DG, et al., Guidelines on management (diagnosis and treatment) of syncope—update 2004, Europace, 2004;6:467–537.
  10. Sanguinetti MC, Jiang C, Curran ME, Keating MT, A mechanistic link between an inherited and an acquired cardiac arrhythmia: HERG encodes the IKr potassium channel, Cell, 1995;81: 299–307.
  11. Roden DM, Drug-induced prolongation of the QT interval, N Engl J Med, 2004;350:1013–22.
  12. Benbadis SR, Allen Hauser W, An estimate of the prevalence of psychogenic non-epileptic seizures, Seizure, 2000;9:280–81.
  13. Scheepers B, Clough P, Pickles C, The misdiagnosis of epilepsy: findings of a population study, Seizure, 1998;7:403–6.
  14. Kennebäck G, Bergfeldt L, Vallin H, et al., Electrophysiologic effects and clinical hazards of carbamazepine treatment for neurologic disorders in patients with abnormalities of the cardiac conduction system, Am Heart J, 1991;121:1421–9.
  15. Goldenberg I, Moss AJ, Zareba W, QT interval: how to measure it and what is “normal”, J Cardiovasc Electrophysiol, 2006;17: 333–6.
  16. Swan H, Toivonen L, Viitasalo R, Rate adaptation of QT intervals during and after exercise in children with congenital long QT syndrome, Eur Heart J, 1998;19:508–13.
  17. Swan H, Viitasalo M, Piippo K, et al., Sinus node function and ventricular repolarization during exercise stress test in long QT syndrome patients with KvLQT1 and HERG potassium channel defects, J Am Coll Cardiol, 1999;34:823–9.