Proceeding of the Symposium on QT prolongation: Antiarrhythmic and arrhythmogenic effects

Idiopathic long QT syndrome: Progress and questions

Congenital long QT syndrome (LQTS) is a hereditary cardiac channelopathy with an estimated prevalence of 1 in 2500. A prolonged resting QT interval corrected for heart rate (QTc interval) remains a key diagnostic component; however, the QTc value may be normal in up to 40% of patients with genotype-positive LQTS and borderline in a further 30%. Provocation of QTc prolongation and T-wave changes may be pivotal to unmasking the diagnosis and useful in predicting genotype. LQTS provocation testing involves assessment of repolarization during and after exercise, in response to changes in heart rate or autonomic tone, with patients with LQTS exhibiting a maladaptive repolarization response. We review the utility and strengths and limitations of 4 forms of provocation testing—stand-up test, exercise stress test, epinephrine challenge, and mental stress test—in diagnosing LQTS and provide some practical guidance for performing provocation testing. Ultimately, exercise testing, when feasible, is the most useful form of provocation testing when considering diagnostic sensitivity and specificity.

Congenital long QT syndrome (LQTS) encompasses a group of heritable conditions that are associated with cardiac repolarization dysfunction. Since its initial description in 1957, our understanding of LQTS has increased dramatically. The prevalence of LQTS is estimated to be ∼1:2,000, with a slight female predominance. The diagnosis of LQTS is based on clinical, electrocardiogram, and genetic factors. Risk stratification of patients with LQTS aims to identify those who are at increased risk of cardiac arrest or sudden cardiac death. Factors including age, sex, QTc interval, and genetic background all contribute to current risk stratification paradigms. The management of LQTS involves conservative measures such as the avoidance of QT-prolonging drugs, pharmacologic measures with nonselective β-blockers, and interventional approaches such as device therapy or left cardiac sympathetic denervation. In general, most forms of exercise are considered safe in adequately treated patients, and implantable cardioverter-defibrillator therapy is reserved for those at the highest risk. This review summarizes our current understanding of LQTS and provides clinicians with a practical approach to diagnosis and management.

Torsades de pointes (TdP) is a type of polymorphic ventricular arrhythmia that is characterized by its hallmark “twisting of peaks” waxing and waning QRS amplitude. TdP may terminate spontaneously or degenerate into ventricular fibrillation, with the potential to result in sudden cardiac death. QT interval prolongation, secondary to inherited or acquired conditions, is intimately associated with TdP. This overview chapter will introduce: (i) definitions and descriptions of TdP; (ii) historical perspectives on TdP; (iii) relationship between long QT syndrome and TdP; (iv) epidemiology of TdP; and (v) consequences of TdP.

The prevention and management of QT interval prolongation and torsades de pointes often depends on the underlying etiology. Drugs and electrolyte imbalances are the major causes of acquired long QT syndrome, and prevention strategies include identifying and discontinuing or substituting the offending drug and correcting electrolyte abnormalities. Lifestyle modification, genetic testing, and β-adrenergic receptor blockade are risk mitigation strategies for patients with the congenital long QT syndrome. Left cardiac sympathetic denervation, implantable cardioverter-defibrillator, magnesium sulfate and overdrive cardiac pacing are currently used in the management of TdP, although a significant number of cases are not adequately managed. This chapter discusses the approaches and current therapies for the prevention and management of long QT syndrome. The chapter also explores novel approaches such genome editing, RNA interference, and hormone therapy in the management of QT interval prolongation and torsades de pointes.