Editorial

Sudden death and the idiopathic long Q-T syndrome

Different genetic types of the long QT syndrome (LQTS) are associated with distinct ECG manifestations, which relate to the type and magnitude of ion channel dysfunction. The QTc duration does not differentiate LQTS types, and therefore other static and dynamic ECG parameters reflecting changes in T wave morphology are used to describe phenotypic expression of different LQTS genotypes. LQT1 carriers usually have broad-based T waves, LQT2 carriers show low-amplitude T waves with high incidence of notches, and LQT3 carriers frequently have extended ST segment with relatively narrow peaked T wave. This phenotypic differentiation could be enhanced by quantifying additional ECG parameters reflecting components of repolarization morphology as well as to evaluate dynamics of repolarization parameters. Heart rate dependency and dynamic behavior of repolarization parameters differ by genotype and further show that genotype indicates ECG phenotype in patients with LQTS. However, there is a substantial variation in repolarization abnormalities observed in the same subject and in the members of the same family indicating large differences in gene penetrance. In conclusion, comprehensive analyses of static and dynamic features of repolarization provide unique opportunity to understand electrophysiology of cardiac repolarization.

The present study was designed to detect the arrhythmogenic effect of mitral valve prolapse, and the relationship between QT, QT dispersion and ventricular arrhythmias in subjects with mitral valve prolapse. Sixty-four mitral valve prolapse subjects (24 men and 40 women, mean age 27 ± 6), and 80 healthy control subjects (32 men and 48 women, mean age 28 ± 7) were studied. The frequency of ventricular arrhythmias by means of 24-h ambulatory electrocardiographic (ECG) monitoring was investigated. Grade ≥ 3 ventricular arrhythmias according to modified Lown and Wolf classification were accepted as complex arrhythmias. The QT intervals were measured from the beginning of depolarization of the QRS complex to the end of the T wave. Using the Bazett formula, QT interval was corrected (QTc) for heart rate. QT dispersion was calculated as the difference between the maximum and minimum QT intervals on any of 12 leads. Premature ventricular complexes seemed to develop in 56 of 64 (87.5%) subjects with mitral valve prolapse. Thirty-eight of the mitral valve prolapse subjects had complex premature ventricular complexes during 24-h ECG and the prevalence of premature ventricular complexes was found to be higher than the control subjects (P < 0.001). We found QT and QTc intervals of 388 ± 27 and 406 ± 33 ms in mitral valve prolapse subjects, these values in control subjects were 382 ± 18 and 402 ± 11 ms respectively (P > 0.05). QT dispersion and QTc dispersion intervals were 71 ± 17 and 78 ± 19 ms in mitral valve prolapse subjects and these values were 43 ± 16 and 52 ± 22 ms in control subjects, respectively (P < 0.001). No correlation was found between complex premature ventricular complexes and QT, but there was a correlation between complex premature ventricular complexes and QT dispersion in the mitral valve prolapse subjects. It was concluded that QT dispersion might be a useful marker of cardiovascular morbidity and mortality due to complex ventricular arrhythmias.

The authors hypothesized that patients with anxious or hostile depression may have a greater risk of mortality from coronary artery disease (CAD) than other depressed patients and therefore proceeded to assess the possible relationship between CAD risk factors and anger and anxiety in a sample of 138 depressed outpatients. The authors observed that increased anxiety scores were associated with higher cholesterol levels and with prolonged QTc intervals. Similarly, the patients with anger attacks tended to have higher cholesterol levels compared with the patients without these attacks. The study's findings partially support the authors’ hypothesis that hostile or anxious depressed patients are at greater risk for CAD than other depressed patients.

Study Objective: To determine if acquired long QT syndrome following right or left, radical or modified, neck dissections result in malignant arrhythmias or deaths.

Design: Prospective study.

Setting: Inpatient head and neck service of the Massachusetts Eye and Ear Infirmary.

Patients: 69 patients who underwent extensive neck surgery, without congenital long QT syndrome, medications known to prolong the QT interval, preoperative ventricular arrhythmias, or electrolyte abnormalities.

Interventions: None.

Measurements and Main Results: Preoperative and postoperative electrolytes were evaluated. Preoperative and postoperative electrocardiograms and QT intervals were evaluated. Continuous intraoperative and 10- to 12-hour postoperative monitoring of lead II or V5 were evaluated. Twenty-six patients (Group 1) underwent either right radical neck dissection or modified right radical neck dissection, 25 patients (Group 2) underwent either left radical neck dissection or modified left neck dissection, and 18 patients (Group 3) underwent extensive neck surgery without radical or modified neck dissection. Postoperatively, 38 patients (19 Group 1, 11 Group 2, and 8 Group 3 patients) developed a QT interval corrected for heart rate (QTc) of greater than 440 milliseconds. Repeated measures analysis of variance, comparing preoperative and postoperative QTc showed a statistically significant preoperative to postoperative change, but no significant difference among the three groups. No malignant arrhythmias or deaths were recorded in any of the three groups.

Conclusions: Acquired long QT syndrome following radical neck dissection, without congenital, metabolic, or pharmacologic disturbance, is unlikely to trigger malignant arrhythmias, as previously reported for right radical neck dissection.

A genomic clone encoding the Shaker-related potassium channel gene, Kcna4/mKv1.4 , was isolated from mice. Its coding region is contained in a single exon, encodes a protein of 654 amino acids, and shares ∼91% nucleotide sequence identity with human KCNA4/hKv.14. We show that 0.8 kb of the 5′ noncoding region (NCR), the entire protein coding region (∼2.0 kb), and all of the known 3′ NCR (∼ 1.1 kb) are contained within a single exon; the remaining 0.5 kb of the 5′ NCR is separated from this exon by a 3.4-kb intron. The sequenced genomic region thus accounts for essentially all of the longest known transcript (4.5 kb), although the precise ends of this transcript have not been defined. The 3′ NCR contains several ATTTA and ATTTG motifs that are thought to destabilize mRNAs, and these are also present in rat, bovine, and human Kcna4/Kv1.4 cDNAs. It also contains three conserved polyadenylation signals, alternate utilization of which could generate mRNAs of differing stabilities. The 5′ NCR of Kcna4/mKv1.4 may also serve to regulate channel expression. This region is ∼85% identical to KCNA4/hKv1.4 and contains eight consensus translation start sites [(G, A)NNATG] that, based on the 5′-3′ scanning model, would lead to a lowering of translational efficiency. The shortest Kcna4/Kv1.4 transcript (2.4 kb) can contain at most 400 bp of NCR and should lack the 3′ ATTTAs and most of the 5′ ATGs; this transcript might therefore exhibit increased stability and translational efficiency. The Kcna4/mKv1.4 channel exhibited biophysical and pharmacological properties indistinguishable from its rat and human homologues. Kcna4/mKv1.4 lies on mouse chromosome 2, near the Fshb locus, and in humans on the proximal half of chromosome 11p14 near human FSHB. Another K⁺ channel gene, Kcnc1/mKv3.1, lies ∼1.8 cM from the Myod-1 gene on mouse chromosome 7, and in situ hybridization localizes KCNC1/hKv3.1 to the homologous region on human chromosome 11p14.3-p15.2. A third gene, KCNA1/hKv1.1, was mapped to human 12p13.

The four Shaker-like subfamilies of Shaker-, Shab-,Shaw-, and Shal-related K⁺ channels in mammals have been defined on the basis of their sequence homologies to the corresponding Drosophila genes. Using interspecific backcrosses between Mus musculus and Mus spretus, we have chromosomally mapped in the mouse the Shaker-related K⁺-channel genes Kcna1, Kcna2, Kcna4, Kcna5, and Kcna6; the Shab-related gene Kcnb1; the Shaw-related gene Kcnc4; and the Shal-related gene Kcnd2. The following localizations were determined: Chr 2, cen-Acra-Kcna4-Pax-6-a-Pck-1-Kras-3-Kcnb1 (corresponding human Chrs 11p and 20q, respectively); Chr 3, cen-Hao-2-(Kcna2, Kcnc4)-Amy-1 (human Chr 1); and Chr 6, cen-Cola-2-Met-Kcnd2-Cpa-Tcrb-adr/Clc-1-Hox-1.1-Myk-103-Raf-1-(Tpi-1, Kcna1, Kcna5, Kcna6) (human Chrs 7q and 12p, respectively). Thus, there is a cluster of at least three Shaker-related K⁺-channel genes on distal mouse Chr 6 and a cluster on Chr 2 that at least consists of one Shaker-related and one Shaw-related gene. The three other K⁺-channel genes are not linked to each other. The map positions of the different types of K⁺-channel genes in the mouse are discussed in relation to those of their homologs in man and to hereditary diseases of mouse and man that might involve K⁺ channels.