1. The Long QT Syndrome: Ion Channel Diseases of the Heart
Michael J. Ackerman, M.D., Ph.D. 
Mayo Clinic Proceedings 
Volume 73, Issue 3, Pages (March 1998)
DOI: /
Copyright © 1998 Mayo Foundation for Medical Education and Research Terms and Conditions

2. Fig. 1
Key clinical characteristics of inherited long QT syndrome (LQTS) are shown, including prolongation of QT interval on electrocardiogram (ECG), commonly associated arrhythmia (torsades de pointes), clinical manifestation, and long-term outcomes. NPV = negative predictive value; PPV = positive predictive value; QTc = corrected QT interval.
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3. Fig. 2
Inherited long QT syndrome (LQTS) pedigree, illustrating family recently identified with Romano-Ward syndrome after near drowning of 10-year-old boy (IV.1). Note that each generation is identified by a rornan numeral, and each individual in a row is numbered consecutively. Thus, drowning victim's (IV.1) maternal grandfather is designated II.2. Beneath each individual is corrected QT interval (QTc) and “Schwartz score” in parentheses. Diagnostic criteria used to obtain score arc shown in inset. ECG = electrocardiogram.
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4. Fig. 3
Molecular blueprint of cardiac ion channel. A, Linear topology of voltagc-galed potassium channel with its six transmcmbrane-spanning segments designated S1 through Sb, voltage sensor(S)4 and pore-forming region (H5). Also highlighted are regions in the channel participating in channel inactivation. Four of these individual, discrete su bunits combine to form the potassium channel. B, Three-dimensional “cartoon” of this assembled potassium channel displayed in its diree distinct confoimational states: closed, open, and inactive. These channel states likely result from dynamic movements of amino acids in the pore (closed), voltage sensor (open), and inactivating mechanism—N-terminus in this illustration (inactive). Of note, pore-forming portion of sodium and calcium channels is derived from a single subunit containing 4-repeats of the basic structural motif shown on top. P = phosphorylation sites.
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5. Fig. 4
Cardiac action potential from clinical, cellular, and molecular perspective. A, Clinical depiction of surface electrocardiogram. QT interval is measured from beginning of QRS complex to return of T wave to isoelectric line. B, Action potential from single ventricular myocyte illustrates predominant currents comprising phase 0 through phase 4. C, Molecular framework of cardiac action potential is displayed, showing linear topologies for defined ion channels. Each ion channel has its amino acid content numbered from beginning to end. Chromosomal site of ion channel gene is in parentheses. Note that representation of IKur is faded in phase 3 because it is primarily an atrial rather than a ventricular current. For explanations of abbreviations, see abbreviation box.
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6. Fig. 5
Molecular basis of long QT syndromes LQT1 through LQT5. Enlarged linear topologies for the four defective ion channels highlight mutations identified thus far. Mutations denoted in red-violet rectangles represent mutations that have been functionally characterized. Orange-highlighted mutations found in LQT1 and LQT5 represent Jervell and Lange-Nielsen (JLN) syndrome mutations. A341V-KVLQT1 mutation (gray) may represent a mutation hot spot in LQT1. Finally, A561T-HERG mutation (violet) for LQT2 has been correlated with peculiar notched T waves on electrocardiogram. Standard nomenclature is used such thai X###Y means that amino acid X has been replaced by amino acid Y at position ###. Of note, KVLQTl mutations have been renumbered based on recent identification of the full-length clone. AP = action potential; bp = base pair; NBD = nucleotide-binding domain. For explanations of other abbreviations, see abbreviation box.
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7. Fig. 6
Simple nomogram requires only a ruler for rapid classifi cation of patients with prolonged (>0.46 sec½), borderline (0.42 to 0.46 sec½), and normal (<0.42 sec½) corrected QT interval (QTc). The 0.42 sec1/2 and 0.46 sec1–1 QTc lines are derived from plotiing QT and R-R coordinates according to QT = QTc × RR½ (Bazett's formula). Assuming paper speed of 25 mm/sec (electrocardiogram standard), a physician can measure QT and R-R interval in millimeters and plot these points on left y-axis and bottom x-axis, respectively. Intersection of these points locates QTc. Alternatively, if patient is in sinus rhythm, physician can plot heart rate on top x-axis instead of measuring R-R interval. In either case (QT versus R-R or QT versus heart rate), if intersection “falls” above shaded region (QTc >0.46 sec½), patient likely has long QT syndrome (LQTS) (false-positive, ∼5%) and should be referred to a cardiologist. If intersection falls below shaded region (that is, QTc <0.42 sec1“), patient is probably normal (false-negative, <2%). Note that 5 to 10% of patients with LQTS will fall within borderline zone; thus, a plot in this zone must be assessed carefully. Certainly, symptoms plus a plot in this borderline zone are compatible with the diagnosis of LQTS. bpm = beats per min.
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8. Fig. 7
Some repolarization abnormalities reflected by T wave on surface electrocardiogram in some patients with long QT syndrome (LQTS). “Peculiar” T waves can be seen in both limb and precordial leads (lead II shown). In fact, “notched” T waves in three leads (tracings 3 and 4) receive 1 point in diagnostic LQTS “Schwartz” score (Fig. 2) and have been associated with A561T mutation in HERG (LQT2). Last tracing showing delayed T-wavc inscription or prolonged QTonset-c may be pheno-typic expression of LQT3 genotype (Table 4). HERG = human ether-a-go-go related gene. (Modified from Moss and Robinson.31 By permission.)
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