Academic Editor: Jerome L. Fleg
In this special issue of Reviews in Cardiovascular Medicine we explore “The Management of Long QT Syndromes”. In broad terms, there are two types of long QT syndromes (LQTS), congenital and acquired [1]. Torsades de Pointes (TdP), first described by Dessertenne in 1966 [2], may self-terminate or degenerate into fatal ventricular fibrillation. TdP may result from either cause of QT prolongation.
Congenital (heritable) long QT syndromes were first described in the 1950s and 1960s. Seventeen genes have been subsequently linked to LQTS [3]. The Clinical Genome Resource (ClinGen), has recent analyzed and reclassified a group of these genes to disputed or limited evidence, leaving seven genes with strong or definitive evidence of causality [3, 4]. Dual genetic abnormalities may complicate management. In genotype negative families, a more complex polygenic architecture may be responsible for QT prolongation [3, 5].
The most common subtypes of congenital LQTS are LQT1 (loss-of-function mutation
in the gene [KCNQ1] that encodes the slow delayed rectifier current
I
Benefits of cardiac pacing in congenital LQTS are less studied and less well defined than its role in acquired LQTS. TdP may be bradycardia or tachycardia dependent in congenital LQTS [7]. There may be benefit for individuals with LQT2 where arrhythmias are almost always pause dependent. LQT3 is particularly associated with QTc prolongation at slow heart rates, suggesting pacing may be beneficial.
Enhanced understanding of the late inward sodium current’s (I
Acquired LQTS most frequently results from drug-induced QT prolongation. The
most common drugs that that prolong QTc block the rapid component of the delayed
rectifier potassium current I
Risk factors for drug-induced TdP include female gender, heart
failure/cardiomyopathy, diastolic dysfunction, myocardial ischemia/infarction,
left ventricular hypertrophy, valvular heart disease, treatment with multiple QT
prolonging drugs or agents that interfere with their metabolism, greater than
average drug dosage, baseline QTc prolongation (
Additional precipitants of acquired LQTS include electrolyte abnormalities (most commonly hypokalemia, hypomagnesemia, and less commonly hypocalcemia), hypothyroidism, and hypothermia. Cardioversion of a rapid supraventricular tachycardia (e.g., atrial fibrillation) after receiving a QT prolonging drug may result in QT prolongation. Recent evidence suggests a high prevalence of QTc interval prolongation in patients with anti-SSA/Ro antibodies, autoimmune and inflammatory diseases [14]. These factors may precipitate acquired LQTS or add to the risk of drug-induced LQTS.
All patients exposed to I
It is widely believed that TdP initiating beats result from early afterdepolarization (EAD)-triggered focal activity from the subendocardial Purkinje network. EADs occur during late phase 2 or phase 3 when action potential duration is increased. The mechanism(s) responsible for perpetuating TdP remain controversial [10].
The initial therapy of choice for acute drug-induced TdP is intravenous magnesium sulfate. Immediate defibrillation is indicated if sustained, hemodynamically unstable polymorphic ventricular tachycardia or ventricular fibrillation develops.
Overdrive transvenous pacing is highly effective in shortening QTc and
preventing arrhythmic recurrence. It is particularly useful when TdP is
refractory to magnesium or when a pause
or bradycardia
precipitates TdP.
Short-term pacing rates of 90 to 110 beats/minute are usually employed. When
temporary pacing is unavailable or during preparation for transvenous catheter
placement, isoproterenol titrated to a heart rate
It is requisite that QT prolonging medications and drugs interfering with their metabolism be promptly discontinued and avoided (if possible) in the future. Electrolyte imbalances must be corrected (serum potassium should be maintained at a level of 4.5–5 mmol/L) [12].
In the setting of acquired long QT syndrome, TdP is almost invariably preceded
by a pause followed by a markedly prolonged QT interval. TdP does not appear to
occur when the effective pacing rate is
While imperfect, management of acquired LQTS is more straightforward than management of congenital LQTS. In a recent review, expert commentary on the management of 4 cases of congenital LQTS revealed agreement on 10 points, disagreement on 3, and acknowledged gaps in knowledge about 8 points [20]. While this special issue of Reviews in Cardiovascular Medicine is unlikely to solve all disagreements or fill every knowledge gap, we hope to enhance readers understanding of LQTS and point future investigations in a direction that will improve our therapeutic armamentarium.
RGT had full access to all the data in the manuscript and takes responsibility for the integrity of the data and the accuracy of the data analysis. RGT—manuscript concept and design, acquisition of data, analysis and interpretation, draft of the manuscript, critical revision of the manuscript for important intellectual content, administrative, technical, and material support.
Not applicable.
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This research received no external funding.
The author declares no conflict of interest. Richard G. Trohman is serving as one of the guest editor of this journal. We declare that Richard G. Trohman had no involvement in the peer review of this article and has no access to information regarding its peer review. Full responsibility for the editorial process for this article was delegated to Jerome L. Fleg. Dr Trohman reported serving as an advisor to Boston Scientific/Guidant; receiving research grants from Boston Scientific/Guidant, Medtronic Inc, St Jude Medical (Abbott), Vitatron, and Wyeth-Ayerst/Wyeth Pharmaceuticals; serving as a consultant for Biosense Webster, Alta Thera Pharmaceuticals and Newron Pharmaceuticals P.s.A.; and receiving speakers fees or honoraria from Boston Scientific/Guidant CRM, Medtronic Inc, Alta Thera Pharmaceuticals, Daiichi Sankyo. and St Jude Medical (Abbott).