Who Is at Risk for Cardiac Events in Young Patients With Long QT Syndrome?

Abstract

ong QT syndrome (LQTS) is a rare disease characterized by prolonged ventricular repolarization and a high risk for cardiac events including sudden cardiac death. 1 Mutations causing LQTS have been identified in 5 genes, each encoding a cardiac ion channel and its regulatory subunit. [2][3][4][5] Most cases of LQTS that come to the attention of physicians are either symptomatic or familial. [6][7][8] Recent studies have reported that life-threatening arrhythmias in LQTS patients tend to occur under specific circumstances (eg, exercise, emotion, and sleep/rest without arousal) in a gene-specific manner. 9 Beta-blocker therapy is reported to be effective in preventing LQTS-related cardiac events in these patients, but they continue to occur while patients are on the prescribed medication. 10 A recent report has reported a gender reference in the electrocardiographic (ECG) response to -blockers in patients with LQTS. 11 A screening program conducted for Japanese children (1st, 7th and 10th grades) has uncovered large numbers of children with LQTS both without a family history and without a history of LQTS-related cardiac events at the Circulation Journal Vol.67, December 2003 time of diagnosis. 12-14 The initiation of drug therapy for these young patients is controversial because many pediatric cardiologists consider that few young LQTS patients without a past history have experienced new cardiac events after diagnosis. The objective of the present study, then, was to examine the characteristics of Japanese pediatric patients with LQTS and to determine the predictive factors for cardiac events after diagnosis in these young patients with and without a past history of cardiac events. Methods Subjects and DataA questionnaire was sent to 111 hospitals where the trustee(s) of the Japanese Society of Pediatric Cardiology and Cardiac Surgery were working. Subjects were those who visited one of those hospitals from January 1997 to August 2000 and who were less than 20 years old at the time of diagnosis. Characteristics of the subjects obtained from the survey included the following: past history of LQTS-related cardiac events, ECG findings, clinical and family history for diagnosis of LQTS according to the criteria of Schwartz et al, 15 cardiac events during the period after diagnosis and medication. When medication was prescribed, those patients were re-surveyed for compliance. Subjects were classified into 2 groups on the basis of the presence or absence of a past history of LQTS-related cardiac events at the time of diagnosis. The index events for diagnosis were classified as follows: (1) Who Is at Risk for Cardiac Events in Young PatientsWith Long QT Syndrome?Masao Yoshinaga, MD*; Masami Nagashima, MD; Toshimitsu Shibata, MD; Ichiro Niimura, MD; Mitsuo Kitada, MD; Toshiaki Yasuda, MD; Mari Iwamoto, MD; Junko Kamimura, MD; Mayu Iino, MD; Hitoshi Horigome, MD; Masashi Seguchi, MD; Sumi Aiba, MD; Naomi Izumida, MD; Takashi Kimura, MD; Hiroya Ushinohama, MD; Junichiro Nishi, MD*; Yukiharu Kono, MD*; Yuichi Nomura, MD*; Ko...

Arrhythmogenesis in the Short-QT Syndrome Associated With Combined HERG Channel Gating Defects

“…We might need to analyze the transmural AP mapping by applying a validated optical mapping technique. 22 Clinically, we have not clearly understood what triggers ventricular tachycardia in the short-QT syndrome unlike the LQTS, 23,24 because adequate genotype-phenotype correlation data are not yet available for the short-QT syndrome. A latest report shows that shortening of the QT interval is prominent at lower heart rates.…”

Guidelines for Risks and Prevention of Sudden Cardiac Death (JCS 2010) - Digest Version -

“…Onset of LQTS during neonatal period and infancy is prevalent among patients with LQT2 or LQT3 mutations, and mexiletine has been reported to be effective in the treatment of LQTS. 174, 175 Poor compliance with drug treatment is a risk factor of arrhythmic accidents. 175 Patients who still have arrhythmias during treatment with antiarrhythmic drugs such as β-blockers and mexiletine, a pacemaker or an ICD is implanted.…”

“…174, 175 Poor compliance with drug treatment is a risk factor of arrhythmic accidents. 175 Patients who still have arrhythmias during treatment with antiarrhythmic drugs such as β-blockers and mexiletine, a pacemaker or an ICD is implanted. [176][177][178][179][180][181] There are no reports of large-scale studies in children with LQTS.…”

Correction of the QT Interval in Children

“…6 In children, a total LQTS score <4 points has been reported as associated with an absence of cardiac events in the future, if the children have no cardiac events in their past history. 7 In pediatric patients with a history of cardiac events, family history of cardiac events, lower medication compliance, and lower age at diagnosis are significant risk factors for a cardiac event in the future. 7 It is well known that the corrected QT interval using Bazett's formula 8 (QTc = QT/RR 1/2 ) is not suitable for use in children whose heart rates are faster than 75 beats/min.…”

“…7 In pediatric patients with a history of cardiac events, family history of cardiac events, lower medication compliance, and lower age at diagnosis are significant risk factors for a cardiac event in the future. 7 It is well known that the corrected QT interval using Bazett's formula 8 (QTc = QT/RR 1/2 ) is not suitable for use in children whose heart rates are faster than 75 beats/min. Fridericia's formula (QTc = QT/RR 1/3 ) is more suitable than Bazett's for correction of the QT interval for lower and also higher heart rates, 9 but it has not become the standard method for the correction of the QT interval.…”