Stanford Cardiac Arrhythmia Service

Long QT Syndrome

Long QT syndrome (LQTS) is an arrhythmia syndrome caused by genetic mutations in a variety of proteins that are critical to regulating the electrical signals that control the heart’s electrical activity. With every normal heartbeat, an electrical signal courses through the heart in a highly controlled fashion. Each portion of the heart must electrically activate, then reset to allow the next beat to follow. The proteins that regulate this process, called ion channels, regulate the flow of sodium, potassium, chloride, calcium, magnesium, and other molecules across heart cells. When an electrocardiogram (ECG or EKG) is performed on a patient, the heart’s electrical activation and reset are being recorded and evaluated.  Activation of each section of the heart is seen on the ECG: the P wave represents atrial activation, the QRS represents left and right ventricular activation, and the QT interval and T wave represent the resetting of the left and right ventricles.

In long QT syndrome, the QT interval, which reflects the lower chambers’ (ventricles’) electrical reset, takes longer than normal. [show ECG with long QT] This leaves the ventricles vulnerable to a potentially dangerous ventricular arrhythmia, called torsades de pointes TdP, where the ventricles’ electrical activation suddenly becomes chaotic and disorganized. [show TdP tracing] During  TdP, the ventricles stop beating efficiently, and blood pressure drops rapidly. If such an episode lasts just a few seconds, the patient may experience palpitations or dizziness. If the episode lasts longer, the patient may faint. If the episode does not stop, the patient will have a cardiac arrest, which may be lethal.

LQTS is generally an inherited disorder, so many cases come to attention during childhood, although many also come to attention in early adulthood or even beyond. There are several, at last count around 10 specific categories of genetic mutations, each leading to slightly different clinical pictures. The three most common subtypes, accounting for more than 95% of cases, are LQT1, LQT2 and LQT3. Each subtype has slightly different ECG characteristics, and each has tendencies towards different clinical pictures. LQT1 patients tend to have episodes of TdP associated with exercise.  LQT2 patients tend to have episodes when startled by loud noises – a stereotypical scenario is an episode of arrhythmia triggered by the sound of an alarm clock.  LQT3 patients, on the other hand, tend to have episodes in their sleep. Furthermore, LQT1 patients tend to have more episodes, but the episodes often stop on their own, so that the episodes are less likely to be fatal. In contrast, LQT3 patients have fewer arrhythmia episodes, but those episodes have a much higher likelihood of being fatal.  A somewhat separate form of LQTS is not clearly an inherited condition, but rather, is the result of taking medications that can prolong the QT interval. There is an extensive list of medications known to potentially prolong the QT interval In patients either with inherited LQTS or who have had a history of drug-induced LQT, these medications should be avoided.

Diagnosis of LQTS, as might be expected is most often made based on an ECG. Patients may come to medical attention having frequent fainting spells, palpitations, or even after surviving a cardiac arrest. Many patients are diagnosed after other family members have been diagnosed.  In addition to the ECG, a stress test is often used to look to see if the QT interval gets shorter with the higher heart rates seen during exercise, which is normally the case. If not, this may suggest the LQT1 subtype.  Genetic testing is becoming more widespread, and may particularly be useful to screen family members of patients known to have the disorder. 

Treatment of LQTS may include medications, avoidance of known triggers, pacemakers, defibrillator (ICD) implantation, or even possibly surgery.  The most often used medications are beta blockers, as they act to blunt the adrenaline response that may trigger some episodes. A more extreme method to blunt the natural adrenaline response is a specialized surgery, cervical sympathectomy, which physically cuts off the adrenaline-related nerve input into the heart. This surgery is not yet considered standard practice, but may be indicated in some cases.  A pacemaker may sometimes be recommended as well. Because the QT interval tends to get longer when the heart rate is slower, leading to a higher risk of an episode of TdP, speeding up the heart rate with a pacemaker may help prevent TdP episodes. When a LQTS patient’s overall case is determined to be high risk, meaning the patient is at high risk of a lethal episode of TdP, a defibrillator (ICD) is often recommended.

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