How is prolonged QT syndrome diagnosed and treated?

From the Guidelines

Diagnosis of prolonged QT syndrome is based on a combination of electrocardiogram (ECG) testing, personal and family medical history, and genetic testing, with a corrected QT (QTc) interval greater than 480 ms or a score ≥3 considered diagnostic. The ECG measures the QT interval, and a QTc interval greater than 480 ms is considered prolonged 1. Treatment depends on the risk level and may include beta-blockers such as nadolol or propranolol as first-line medications to reduce sympathetic stimulation of the heart.

Key Considerations

• Lifestyle modifications are essential for all patients, including avoiding QT-prolonging medications, maintaining normal electrolyte levels, and avoiding triggers like intense physical activity or emotional stress 1.
• Genetic testing can identify a disease-causing mutation in 75% of LQTS cases, with three main genes (KCNQ1, KCNH2, and SCN5A) accounting for 90% of positively genotyped cases 1.
• Beta-blockers are recommended in patients with a clinical diagnosis of LQTS, and ICD implantation with the use of beta-blockers is recommended in LQTS patients with previous cardiac arrest 1.

Treatment Options

• Beta-blockers: nadolol (40-80 mg daily) or propranolol (10-40 mg three times daily) as first-line medications to reduce sympathetic stimulation of the heart.
• ICD implantation: recommended for high-risk patients or those who continue to have symptoms on beta-blockers to prevent sudden cardiac death.
• Lifestyle modifications: essential for all patients, including avoiding QT-prolonging medications, maintaining normal electrolyte levels, and avoiding triggers like intense physical activity or emotional stress.
• Genetic testing: can identify a disease-causing mutation in 75% of LQTS cases, and guide specific additional treatments, such as mexiletine for LQT3 1.

From the Research

Diagnosis of Prolonged QT Syndrome

• The diagnosis of prolonged QT syndrome primarily rests on clinical and electrocardiographic features and family history 2.
• The assessment of the QT interval has been an integral part of ECG interpretation, and the correct measurement of the QT interval should be performed by using the "tangent method", excluding possible U waves 3.
• A heart rate correction formula should be employed to determine the heart rate corrected QT interval (QTc) 3.
• Many factors, which may prolong the QT interval, should be checked whenever a QTc prolongation is observed, including drugs, electrolyte imbalances, hormonal influence, and comorbidities 3.

Treatment of Prolonged QT Syndrome

• The therapeutic approaches for LQTS are multimodal, and prevention is the basis of the therapy, including avoiding known risk factors and potentially QT-prolonging drugs, and a pharmacological treatment with non-selective beta blockers 3.
• According to the risk profile and to the patient's lifestyle, the implantation of an ICD or a pacemaker should be considered 3.
• Short-term treatment of LQT is aimed at preventing the recurrences of torsades and includes intravenous magnesium and potassium administration, temporary cardiac pacing, withdrawal of the offending agent, correction of electrolyte imbalance, and, rarely, intravenous isoproterenol administration 2.
• Long-term treatment is aimed at reducing the QT-interval duration and preventing the torsades and sudden death and includes use of oral beta-adrenergic blockers, implantation of permanent pacemaker/cardioverter-defibrillator, and left thoracic sympathectomy 2.

Risk Stratification and Management

• The correct management of a patient with (genetically determined) LQTS starts with a risk stratification based on genotype, ECG phenotype, clinical history, age, sex, concomitant diseases, drug therapies, and family history for syncope or sudden cardiac death 3.
• Device therapy, although effective, is not without complications and should be reserved for high-risk patients 4.
• Beta-blockers are the treatment of choice to reduce cardiac symptoms, and long-term follow-up of genotyped families with LQTS has shown that beta-blocker therapy can be effective and safe 5.