Severe QT Research Articles

Elevated serum gastrin levels in Jervell and Lange-Nielsen syndrome: A marker of severe KCNQ1 dysfunction?

The potassium channel I(Ks), which is encoded by the KCNQ1 gene, is expressed in organ systems including the inner ear, kidneys, lungs, intestine, and stomach in addition to the heart. Increasing evidence indicates that I(Ks) in the stomach plays an essential role in enabling gastric acid production. It is not known whether gastric acid production is disordered in patients with long QT type 1. Serum gastrin levels become elevated in subjects with disordered gastric acid production. The purpose of this study was to evaluate serum gastrin levels, as a surrogate for impaired gastric acid secretion, in patients with KCNQ1 mutations, and to see if gastrin levels correlate with severity of cardiac disease. Fasting serum gastrin levels were measured using a standardized immunometric technique in an index case and 12 subjects with known KCNQ1 mutations. An adult female with Jervell and Lange-Nielsen syndrome (JLNS; with KCNQ1 nonsense mutations p.Arg518X and p.Arg190AlafsX95 ) presented with multiple gastric carcinoid tumors and grossly elevated serum gastrin levels (943-1,570 pmol/L; normal 6-55 pmol/L) and absent acid secretion. Gastrin levels in two girls with JLNS, unrelated to the index case (missense mutations p.Leu266Pro and Gly269Ser), also were high (305 and 229 pmol/L). Gastrin levels were normal in 10 KCNQ1 heterozygous single mutation carriers, even in those with severe long QT syndrome, including three heterozygous family members of the JLNS subjects. JLNS may be associated with elevated gastrin levels, impaired acid secretion, and risk of gastric carcinoid tumors. Among KCNQ1 single mutation carriers, gastrin levels were normal and did not appear to be linked to the severity of clinical expression of long QT syndrome.

Fragmented QRS is associated with torsades de pointes in patients with acquired long QT syndrome

Acquired long QT syndrome (LQTS) is a disease due to a secondary repolarization abnormality induced by various predisposing factors. In contrast to congenital LQTS, risk factors that produce acquired LQTS include organic heart diseases that often exhibit depolarization abnormality. Although various repolarization parameters have been evaluated in acquired LQTS, the existence of depolarization abnormality in association with torsades de pointes (TdP) has not been reported. The purpose of this study was to evaluate both repolarization (QT components) and depolarization parameters (fragmented QRS [fQRS]) in acquired LQTS patients with markedly prolonged QT interval. Seventy patients with acquired severe QT prolongation (QTc ≥ 550 ms) were studied. Thirty-two patients had syncope or TdP (syncope group). Thirty-eight patients did not have any symptoms (asymptomatic group). The existence of fQRS and QT components (QT, QTc, Tpe [interval between peak and end of T wave] intervals, and U-wave voltage) was analyzed. The syncope group had more frequent fQRS (81%) than did the asymptomatic group (21%, P < .01) and the incidence of fQRS was not different before and after removal of predisposing factors. The incidence of organic heart disease was not different between the two groups. No differences in QTc interval were noted between the syncope and asymptomatic groups, although the syncope group had longer QT and Tpe intervals and higher U wave than the asymptomatic group (P < .01). Acquired predisposing factors promoted repolarization abnormality (especially prolongation of QT and Tpe intervals), and the existence of fQRS had an important role in the development of TdP in patients with acquired LQTS.

A case of torsades de pointes induced by severe QT prolongation after an overdose of eperisone and triazolam in a patient receiving nifedipine

Introduction. Eperisone hydrochloride is a centrally acting muscle relaxant, and triazolam is a short-acting benzodiazepine. Although commonly prescribed, cardiotoxicity induced by a single overdose of either drug is comparatively rare. A patient receiving nifedipine developed torsades de pointes (TdP) because of prolongation of the corrected QT (QTc) interval after an overdose of eperisone hydrochloride and triazolam. Case report. A 60-year-old man receiving nifedipine was admitted in a comatose condition 3 h after ingesting 5,000 mg of eperisone and 2.5 mg of triazolam. Electrocardiogram showed sinus rhythm with prolongation of the QTc interval (820 ms). The serum electrolyte levels were as follows: potassium, 3.8 mEq/L; magnesium, 2.4 mg/dL. The serum drug concentrations were high: eperisone, 15,360 ng/mL; triazolam, 110.8 ng/mL. A temporary cardiac pacemaker was implanted immediately after the development of TdP, 11 h after the ingestion. The serum triazolam concentration normalized on day 2. The QTc interval and eperisone concentration normalized on day 6. Conclusion. Eperisone and triazolam overdose can cause life-threatening cardiotoxicity. Electrocardiographic monitoring and serial determination of QTc interval are likely the best way to observe these patients and evaluate the risk of cardiotoxicity.

Severe QT interval prolongation associated with moxifloxacin: a case report.

IntroductionThe QT interval prolongation is an adverse effect associated with moxifloxacin. This adverse effect can lead to potentially life-threatening arrhythmias such as Torsades de pointes. We describe a case of severe QT interval prolongation associated with moxifloxacin which may cause the development of Torsades de pointes. There have been no reported case of severe corrected QT interval prolongation caused by moxifloxacin in the patient of normal heart rate.Case presentationIn an 85-year-old Japanese woman, oral moxifloxacin 400 mg daily was initiated for the forearm cellulitis. On the sixth day of oral moxifloxacin administration, monitor electrocardiogram showed prolongation of the corrected QT interval to 523 ms at a rate of 40 beats/min. Electrocardiogram before moxifloxacin therapy showed the corrected QT interval to 460 ms at a rate of 72 beats/min. On the sixth day after moxifloxacin discontinuance, monitor electrocardiogram showed the corrected QT interval to 432 ms at a rate of 70 beats/min.ConclusionThis case suggests that electrocardiogram monitoring during moxifloxacin therapy may be necessary in the patients even if they do not have high risk factors for QT interval prolongation.

Syndactyly and long QT syndrome (Ca V1.2 missense mutation G406R) is associated with hypertrophic cardiomyopathy

ong QT syndrome (LQTS) is a heterogeneous ion channel isorder caused by mutations in either the cardiac potassium hannel genes or the cardiac sodium channel gene SCN5A. anifestations of LQTS during fetal or neonatal life are ncommon and usually indicate a severe form of the disase. A specific cardiac L-type calcium channel dysfuncion has been reported to cause LQTS and syndactyly. This isorder, also called Timothy syndrome, is caused by the de ovo CaV1.2 missense mutation G406R. It appears to be a ultiorgan disease that includes congenital heart disease, ecurrent infections, hypoglycemia, and autism. The synrome is characterized by severe QT prolongation and lethal entricular arrhythmias in the first years of life. In this eport, we describe two neonates with Timothy syndrome nd extend the phenotype to include hypertrophic cardioyopathy and ventricular systolic dysfunction.

Compound heterozygosity for mutations Asp611→Tyr in KCNQ1 and Asp609→Gly in KCNH2 associated with severe long QT syndrome

LQTS (long QT syndrome) is an inherited cardiac disorder characterized by prolongation of QT interval, torsades de pointes and sudden death. We have identified two heterozygous missense mutations in the KCNQ1 and KCNH2 (also known as HERG) genes [Asp611-->Tyr (D611Y) in KCNQ1 and Asp609-->Gly (D609G) in KCNH2] in a 2-year-old boy with LQTS. The aim of the present study was to characterize the contributions of the mutations in the KCNQ1 and KCNH2 genes relative to the clinical manifestations and electrophysiological properties of LQTS. Six of 11 carriers of D611Y in KCNQ1 had long QT intervals. D609G in KCNH2 was detected only in the proband. Studies on the electrophysiological alterations due to the two missense mutations revealed that the D611Y mutation in KCNQ1 did not show a significant suppression of the currents compared with wild-type, but the time constants of current activation in the mutants were increased compared with that in the wild-type. In contrast, the D609G mutation in KCNH2 showed a dominant-negative suppression. Our results suggest that the mild phenotype produced by the D611Y mutation in KCNQ1 became more serious by addition of the D609G mutation in KCNH2 in the proband.

Isolated T wave alternans

Two patients with isolated T wave alternans are reported, with their vectocardiograms, their response to carotid sinus stimulation, and the response to calcium infusion in one of them with documented severe hypocalcemia. Eleven cases of the literature are briefly reviewed. The alternans of the T wave appears with severe QT prolongation, QT alternans, and an increased tendency to ventricular fibrillation. The findings are consistent with the hypothesis that T wave alternans may be the electrocardiographic manifestation of the transmembrane action potential alternans and could be related in some cases to hypocalcemia.