Long QT syndrome

There are two main causes of Long QT: acquired Long QT and congenital Long QT.

Acquired Long QT syndromes

Acquired Long QT syndromes are reversible causes of QT interval prolongation. They are due to medication use, toxins, or metabolic disorders that interfere with the function of certain ion channels (most often potassium channels).

Among the metabolic disorders involved are low potassium (hypokalemia), low magnesium (hypomagnesemia), and low calcium (hypocalcemia).

The list of medications and toxins implicated in QT interval prolongation is extensive. This list can be provided by your electrophysiologist at Rythmopôle Paris, who will help you identify high-risk medications in your treatment. The most common include:

• Certain antiarrhythmics (quinidine, amiodarone, sotalol)
• Certain antibiotics (macrolides: azithromycin, erythromycin; quinolones)
• Certain antimalarials: quinine and quinoline derivatives
• Certain psychotropic drugs (tricyclic antidepressants)
• Antihistamines

In many cases, QT interval prolongation is not caused by a single factor but by the combination of several factors (for example: use of multiple QT-prolonging medications together with hypokalemia).

Congenital Long QT syndromes

Congenital Long QT syndromes are rare genetic, hereditary conditions caused by mutations in one or more genes regulating certain ion channels involved in repolarization (most often potassium or calcium channels). They require specialized management by an electrophysiologist.

Genetic classification of congenital forms

Congenital Long QT syndromes are classified into different types (LQT1 to LQT17) according to the mutated gene. The three most common types—LQT1, LQT2, and LQT3—account for about 75% of cases. This genetic classification has clinical significance because some types are associated with specific triggers (exercise for LQT1, emotion or noise for LQT2, rest or sleep for LQT3) and influence therapeutic choices.

Inheritance and family screening

Congenital Long QT syndromes are most often inherited in an autosomal dominant pattern, meaning that an affected patient has a 50% chance of passing the mutation to each child. Following the diagnosis of congenital Long QT in a patient, systematic screening is recommended for first-degree relatives (parents, siblings, children) through a standard electrocardiogram and, if available, genetic testing for the mutation identified in the index case. This screening can be carried out at Cardiopôle Yvart (Paris 15th), which has the necessary equipment for a complete evaluation.

In many cases, Long QT syndrome is asymptomatic. It then manifests as a prolonged QT interval that can only be diagnosed with an electrocardiogram. However, a severe prolongation of the QT interval exposes patients to serious ventricular arrhythmias called torsades de pointes, which can themselves degenerate into ventricular fibrillation.

These ventricular rhythm disturbances are characterized by a sudden and significant acceleration of the heart rate, which the patient may experience as palpitations or dizziness. The most severe forms can lead to loss of consciousness or even cardiac arrest. These manifestations are among the most concerning Long QT symptoms.

High-risk situations

Certain situations may trigger arrhythmias in patients with Long QT syndrome:

• Intense physical exercise (particularly swimming for LQT1)
• Strong emotions or stress
• Sudden loud noises (alarm clock, alarms)
• Postpartum period
• Periods of fasting or strict dieting

Knowing these triggering factors allows preventive measures to be adapted according to the type of Long QT syndrome diagnosed.

The diagnosis of Long QT syndrome is based primarily on the standard electrocardiogram (ECG Long QT), which measures the QT interval and identifies its abnormal prolongation. This measurement is compared to normative values that take into account the patient’s heart rate and sex.

Additional diagnostic methods

In addition to the standard electrocardiogram, other tests may be used to confirm or refine the diagnosis:

• The Long QT exercise test, which can reveal abnormal QT interval behavior during exertion
• 24–48 hour Holter ECG, allowing the detection of intermittent abnormalities
• The adrenaline pharmacological test, used in certain specialized centers such as Institut Mutualiste Montsouris (Paris 14th)
• Molecular genetic analysis, essential as part of a Long QT genetic analysis, to identify the causal mutation

The assessment of the risk of rhythm-related complications is an essential step in management and involves several factors:

• The duration of the corrected QT interval (QTc): the greater the prolongation, the higher the risk of complications
• The genetic type of syndrome: certain types (such as LQT1, LQT2, LQT3) are associated with a particular risk profile
• Personal history of syncope or cardiac arrest
• Family history of serious cardiac events
• The patient’s sex (women generally present a higher risk, especially after puberty)
• The age at which the first symptoms occur (the earlier they appear, the higher the risk)

This risk stratification enables the electrophysiologist at Rythmopôle Paris to develop an individualized management plan for each patient.

The management naturally depends on the cause of the Long QT. The Long QT treatment is therefore adapted according to whether it is an acquired or congenital form.

In the case of acquired Long QT syndrome

Treatment consists of correcting the triggering factor:

• Stopping the medication(s) responsible
• Correcting a metabolic disorder

In addition, hospitalization may sometimes be necessary if the disorder is severe or symptomatic (dizziness, palpitations), until it is corrected. However, the optimal approach is actually preventive. It is important to avoid combining QT-prolonging drugs, to screen for and promptly correct aggravating electrolyte disturbances, and to check the electrocardiogram when prescribing a high-risk medication.

In the case of congenital Long QT syndrome

Management is handled by a specialist (electrophysiologist) and is structured around several key aspects:

First, avoidance of aggravating factors:

• Contraindication to QT-prolonging medications: list to be given to the patient
• Early detection and treatment of aggravating metabolic disorders (potassium, magnesium, calcium)
• Avoid stress and intense competitive sports

Second, genetic and family investigation:

This involves identifying the causal mutation. This allows for better follow-up, risk stratification, and screening for the identified mutation in the patient’s relatives for early diagnosis and treatment. This is done with a simple blood test. However, results may take a long time to obtain (several months).

Finally, specific treatment:

• Beta-blocker drug therapy: recommended for all patients with congenital Long QT. This Long QT beta-blocker significantly reduces the arrhythmic risk. The most commonly used is nadolol (Corgard).
• Other treatments (less frequently required):
  • Placement of a Long QT implantable defibrillator – this treatment concerns only a small number of patients
  • Cardiac sympathetic denervation

These advanced treatments are available at Institut Mutualiste Montsouris (Paris 14th), where the electrophysiologists of Rythmopôle Paris perform all arrhythmia ablation procedures and implantable device placements.

Physical activity

Recommendations regarding physical activity depend on the genetic type and severity of Long QT syndrome:

• For patients with LQT1, swimming and water sports are generally contraindicated
• Intense competitive sports are often discouraged for all types
• Regular moderate physical activity remains beneficial and is encouraged in most cases
• Specific restrictions may be defined by the electrophysiologist based on the individual profile

Professional life

The majority of patients can work without particular restrictions. However, certain professions involving specific risks (pilot, professional driver, working at heights) may be subject to limitations depending on the severity of the syndrome.

Pregnancy and family life

• Pregnancy is generally well tolerated in patients with Long QT syndrome
• Specific rhythm monitoring is recommended during pregnancy and the postpartum period
• The postpartum period is a time of increased vigilance, particularly in women with LQT2
• Family screening is essential to identify other potentially affected family members

With appropriate management, most patients with Long QT syndrome can lead an active life. Risk stratification, performed by the electrophysiologist, allows for individualized recommendations regarding physical activity, professional life, and daily living. Adherence to drug treatment and compliance with medication contraindications are essential to reduce the risk of complications.

Rythmopôle Paris has specific expertise in the management of Long QT syndrome:

• A team of electrophysiologists specializing in the diagnosis and management of cardiac rhythm disorders
• Fully equipped technical facilities for carrying out all necessary diagnostic tests: standard ECG, Holter ECG, exercise test
• The possibility of performing specific tests such as the adrenaline test at Institut Mutualiste Montsouris
• A dedicated cardio-genetics consultation at Cardiopôle Yvart allowing for coordinated family screening
• Personalized follow-up with the possibility of implantable device checks in several centers across the Île-de-France region, including Cardiopôle Peupliers-Trubert
• A multidisciplinary approach integrating recommendations on physical activity and daily life tailored to each patient

Long QT syndrome requires electrophysiology expertise for its diagnosis and follow-up. Patients with suggestive symptoms or a family history will benefit from a specialized evaluation