Endgames Case Report

A heart stopping performance

BMJ 2012; 345 doi: http://dx.doi.org/10.1136/bmj.e6076 (Published 20 September 2012) Cite this as: BMJ 2012;345:e6076
  1. Joyee Basu, foundation year 2 trainee1,
  2. Timothy Betts, consultant cardiologist 2
  1. 1Stoke Mandeville Hospital, Aylesbury HP21 8AL, UK
  2. 2John Radcliffe Hospital, Oxford, UK
  1. Correspondence to: J Basu joyeebasu11{at}yahoo.co.uk

After a show jumping round at a local horse show, a 23 year old woman who had been competing slumped and fell from her horse. An onsite paramedic immediately administered basic life support. An ambulance crew arrived shortly afterwards and performed electrocardiography (ECG), which showed ventricular fibrillation. A single shock was administered before the return of spontaneous circulation.

On arrival at the intensive care unit, she was intubated and ventilated. She was cooled for 24 hours and given inotropic support. On clinical examination she was unresponsive, tachycardic, and hypotensive. There were no other positive findings on clinical examination. Blood results (including calcium, magnesium, potassium, and troponin measurements), toxicology screen, septic screen, and computed tomography of the head were negative. She was taking no regular drugs and had no history of cardiac problems or a family history of cardiac arrest or sudden death. ECG performed before cooling and on discharge from intensive care confirmed the diagnosis of long QT syndrome. An echocardiogram showed a structurally normal heart. She later had a dual chamber implantable cardioverter defibrillator fitted and was treated with an oral β blocker.

Questions

  • 1 What is the definition of a long QT interval?

  • 2 What are the common causes of long QT syndrome?

  • 3 Which clinical criteria are used to diagnose long QT syndrome?

  • 4 What is the risk of sudden cardiac death with long QT syndrome?

  • 5 What is the treatment strategy for long QT syndrome?

  • 6 What advice would you give a patient with newly diagnosed long QT syndrome?

Answers

1 What is the definition of a long QT interval?

Short answer

When corrected for rate, a QT interval of greater than 450 ms in males and greater than 460 ms in females is considered abnormal.1 The average corrected QT interval in patients with genetically confirmed long QT syndrome is 490 ms. The QT interval is best measured in leads II, V5, and V6.

Long answer

The QT interval is the interval between the beginning of the Q wave and the end of the T wave (fig 1). It represents the time taken for ventricular depolarisation and repolarisation. The QT interval is dependent on heart rate—the faster the heart rate the shorter the QT interval, and vice versa. To account for this, Bazett’s formula is used to calculate the corrected QT interval (QTc). This is the measured QT interval divided by the square root of the R-R interval (QTc=QT/√R-R). The longer the QTc the more likely the patient is to have a genetic abnormality and cardiac event. Sex differences in the definition of a long QT interval are thought to result from the differential expression of cardiac membrane channels in the two sexes.

Figure1

Fig 1 Example of the measurement of the corrected QT interval (QTc)

2 What are the common causes of long QT syndrome?

Short answer

Subtypes 1-3 are the most common congenital variants of the syndrome. Several drugs, as well as severe electrolyte imbalances, may result in acquired long QT syndrome.

Long answer

The syndrome can be divided into congenital and acquired forms. Type 1 is the most common congenital form, accounting for 40-45% of cases, with type 2 and type 3 accounting for 20-25% and 5-10% of cases, respectively. A further seven different genetic mutations have also been described. Table 1 shows the three most common mutations. Gene mutations affect a subunit of a protein, in turn affecting ionic currents, most commonly in the cardiac cell potassium channel (types 1 and 2) or sodium channel (type 3). Inheritance is often autosomal dominant (Romano-Ward syndrome) but may also be autosomal recessive (Jervell and Lange-Nielsen syndrome) or polygenic.

Table 1

Genetics of the 3 main subtypes of the long QT syndrome (all inherited in an autosomal dominant manner)2

View this table:

Patients commonly present with syncope or cardiac arrest (or both) and often have a family history of blackouts or sudden death. In each subtype there may be specific triggers for cardiac events. Most cardiac events occur during exercise (62%) in those with type 1 disease.3 Cardiac events in patients with type 2 disease typically occur when they are startled by loud auditory stimuli. In patients with type 3 disease, events occur during rest or sleep. Although patients with type 1 and type 2 disease may have more frequent symptoms, events are more likely to be fatal in those with type 3 disease.

It has been proposed that the three common subtypes can be identified by characteristic appearances of the T wave—broad based and prolonged in type 1 disease, biphasic and notched in type 2, and appearing late with a prolonged isoelectric segment in type 3. The use of genetic testing has largely superseded this form of subtyping.

Table 2 outlines important acquired causes of long QT syndrome.

Table 2

Important acquired causes of long QT syndrome

View this table:

This list is not exhaustive and further information on drugs that may cause QT prolongation and should be avoided in this syndrome can be found at www.qtdrugs.org and www.azcert.org.

Patients with congenital long QT syndrome are also at higher risk of QT prolongation than the general population when taking these drugs. Acquired long QT syndrome that is induced by the use of a QT prolonging drug is likely to be genetically mediated. It has been postulated that acquired long QT syndrome may be caused by a mutation that does not become clinically apparent until the patient has been exposed to a QT prolonging drug.4 5 Furthermore, patients may have silent mutations (gene mutations with low penetrance) where the QT interval is normal at rest. However, when exposed to QT prolonging drugs the QT interval increases.6 Mutations may also lead to moderate increases in the QT interval, which lengthen further with the addition of a QT prolonging drug.7 Even in people without long QT syndrome, the QT interval will lengthen if a high enough dose of one of these drugs, or a combination of these drugs, is given.

3 Which clinical criteria are used to diagnose long QT syndrome?

Short answer

The Schwartz criteria can categorise patients into a low, intermediate, or high probability of having long QT syndrome.

Long answer

A long QT interval on electrocardiography does not necessarily imply that the patient has long QT syndrome. The syndrome includes features such as palpitations, syncope, and cardiac arrest. The patient must be assessed further by taking a comprehensive history, including previous symptoms of palpitations, syncope, and cardiac arrest; drug history; and family history of syncope and sudden cardiac death. The finding of a long QT interval should be placed in the context of the clinical picture as a whole.

The Schwartz criteria (box) provide a diagnostic tool for categorising patients into low, intermediate, or high probability of having the syndrome.8 The tool is based on points scored for aspects of clinical history, listed above, as well as ECG findings.

Schwartz criteria for categorising patients with long QT syndrome

Clinical history
  • Syncope (cannot receive points for both syncope and torsades de pointes)

    • With stress=2 points

    • Without stress=1 point

  • Congenital deafness=0.5 points

Family history (the same family member cannot be counted for LQTS and sudden death)
  • Family members with definite long QT syndrome=1 point

Unexplained sudden cardiac death below age 30 years in immediate family=0.5 points

Electrocardiographic findings
  • Corrected QT interval (QT interval divided by the square root of the R-R interval):

    • > 0.48 s=3 points

    • 0.46-47 s=2 points

    • 3. 0.45 s and male=1 point

  • Torsades de pointes=2 points (not counted if also have history of syncope)

  • Visible T wave alternans (beat to beat variation in the amplitude of the T wave)=1 point

  • Notched T wave in at least 3 leads=1 point

  • Low heart rate for age (children)=0.5 points

  • High risk 4 points; intermediate risk 2-3 points; low risk ≤1 point

In addition, patients usually undergo an exercise test, which can provide information on the exercise recovery QT interval. A QT interval of greater than or equal to 480 ms at the fourth minute of recovery suggests that the patient has type 1 or 2 disease. Genetic testing may be used to confirm the diagnosis and will identify a genetic mutation in 75-80% of patients.

In patients with a long QT interval who do not meet the criteria for long QT syndrome, QT prolonging drugs should be stopped or substituted if possible. In addition, electrolyte abnormalities such as hypomagnesaemia, hypokalaemia, and hypocalcaemia should be corrected. If a repeat ECG shows a long QT interval, refer the patient to a cardiologist, and advise the patient to avoid QT prolonging drugs in the meantime.

4 What is the risk of sudden cardiac death with long QT syndrome?

Short answer

Female sex, a QTc interval of greater than 500 ms, and a history of syncope or previous cardiac arrest are the strongest predictors of sudden cardiac death.

Long answer

The overall risk of sudden cardiac death in those receiving appropriate treatment is low (0.1-0.6% each year).9 10 Risk is higher in females, especially as they get older. Male patients tend to have more events during childhood. Compared with a QTc interval less than 499 ms, risk is increased 3.3-fold and sixfold in patients with an interval greater than 500 ms and 550 ms, respectively. A history of syncope increases the risk sixfold. Patients with type 2 disease are most likely to have a cardiac event, including syncope, but the overall risk of sudden death does not differ between genotypes. A family history of sudden cardiac death does not seem to increase risk.

5 What is the treatment strategy for long QT syndrome?

Short answer

Management depends on presentation. Patients who have a cardiac arrest because of torsades de pointes (polymorphic ventricular tachycardia) or ventricular fibrillation should be treated promptly according to Resuscitation Council UK guidelines. In the outpatient setting, most patients are prescribed a β blocker. An implantable cardioverter defibrillator is offered to survivors and high risk patients (such as those with syncope despite β blockers). High intensity sports and QT prolonging drugs should be avoided.

Long answer

In the acute setting a broad complex tachycardia should be managed in the following manner. For all pulseless rhythms the advanced life support cardiac arrest protocol should be followed.11 If the patient has a pulse but adverse features (such as shock, syncope, myocardial infarction, heart failure) up to three synchronised direct current shocks may be given. This is followed by 300 mg intravenous amiodarone over 20 minutes, then 900 mg over 24 hours. If the patient is not compromised, a regular broad complex tachycardia is managed with 300 mg intravenous amiodarone over 20 minutes, followed by amiodarone 900 mg over 24 hours. If the rhythm is irregular an expert opinion must be sought. The possible rhythms include atrial fibrillation with bundle branch block (manage as a narrow complex tachycardia) and pre-excited atrial fibrillation, such as in those patients with Wolff-Parkinson-White syndrome (consider flecainide) and torsades de pointes (stop all QT prolonging drugs, correct hypokalaemia, and give 2 g magnesium over 10 minutes). Figure 2 summarises the management of broad complex tachycardias.

Figure2

Fig 2 Summary of the management of broad complex tachycardias; adapted from Resuscitation UK guidelines

The management of cardiac arrest in patients with long QT syndrome may be particularly challenging. The catecholamine surge associated with a life threatening event can provoke recurrent arrhythmias. Patients should be sedated and given β blockers. Temporary pacing to increase the heart rate and shorten the QT interval may also be of use because torsades de pointes often occurs after a relative pause. Electrolyte abnormalities should be corrected and QT prolonging drugs stopped. In this particular setting, amiodarone and sotalol should be avoided.

β blockers significantly reduce cardiac events in these patients, particularly those with type 1 and type 2 disease.12 13 Left cardiac sympathetic denervation is a second line treatment that requires a small incision in the left subclavicular area and removal of the first four thoracic ganglia. In a study of selected patients who underwent this treatment, the average number of cardiac events per patient per year fell by 91% (P<0.001).14 Left cardiac sympathetic denervation has been superseded by implantable cardiac defibrillators for the treatment of high risk patients and now is rarely performed.

Implantation of a cardiac defibrillator is first line treatment after cardiac arrest or in patients with recurrent syncope despite β blocker treatment.15 It is difficult to identify asymptomatic patients who are at high risk, but a prophylactic cardiac defibrillator may be offered to those with a strong family history of sudden cardiac death at a young age, especially if type 3 disease has been identified. These devices also have the advantage of performing pacing, thereby avoiding bradycardic episodes that may precipitate torsades de pointes. The devices are not without their problems. They do not prevent the occurrence of arrhythmias, and—although these are often self limiting, the release of catecholamines triggered by the shock can lead to further arrhythmias and further discharges. Figure 3 summarises the treatment options in patients with long QT syndrome.

Figure3

Fig 3 Treatment options in patients with long QT syndrome

6 What advice would you give a patient with newly diagnosed long QT syndrome?

Short answer

Advise patients to avoid strenuous high intensity exercise, sudden acoustic stimuli such as alarm clocks and loud telephones, and QT prolonging drugs. Provide information on electrolyte abnormalities, such as hypomagnesaemia, hypocalcaemia, and hypokalaemia, which may precipitate cardiac events. First degree family members should undergo genetic screening.

Long answer

The European Society of Cardiology guidelines state that patients should avoid competitive sports.16 Specifically, patients with type 1 disease should avoid swimming unsupervised, and those with type 2 and type 3 disease should avoid acoustic stimuli, such as telephones and alarm clocks. Partners and families should be given advice on cardiopulmonary resuscitation, and the purchase of a home defibrillator should be considered if the patient does not have an implantable cardiac defibrillator.17 All patients should be aware of the drugs (fig 3) that can prolong the QT interval and ensure that they discuss the risks of any newly prescribed drug, as well as over the counter formulations, with their general practitioner or hospital team. Because the syndrome can be inherited, patients must be made aware that their relatives may be affected. First degree relatives should undergo clinical evaluation, including a comprehensive history, ECG,18 and an exercise test, because the exercise test can help identify patients with type 1 and 2 disease.

Mutation specific genetic testing is recommended for first degree family members after the identification of a mutation in a patient.18

Patient outcome

The patient had a cardiac defibrillator implanted and she was started on a β blocker.

Notes

Cite this as: BMJ 2012;345:e6076

Footnotes

  • Competing interests: Both authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare: no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.

  • Provenance and peer review: Not commissioned; externally peer reviewed.

  • Patient consent obtained.

References