Diurnal and heart rate dynamics of QT interval in symptomatic and asymptomatic affected family members of long QT syndrome

Background. The long QT syndrome (LQTS), a leading cause of sudden death under 20 years of age, is due to mutations in genes which encode ion channels involved in the control of ventricular repolarization. In a prospective study on 34,000 neonates we found that a prolonged QT interval was associated with a 41 times greater risk for sudden infant death syndrome (SIDS) and, recently, in a case-control study on 201 cases of SIDS we found disease-causing LQTS mutations in 9.5% of the victims. Based on these results the Italian Ministry of Health is considering the possibility of introducing in the National Health Service an electrocardiographic (ECG) screening program in the first month of life to identify infants affected by LQTS. A realistic assessment of the prevalence of infants with LQTS becomes necessary. Methods. An ECG was recorded in the first month of life in 44,596 neonates. The QT interval was measured and corrected for heart rate according to the Bazett’s formula (QTc). In the neonates with a markedly prolonged QT (QTc ≥ 470 msec) molecular screening of the LQTS genes was performed. Results. A QTc between 440 and 470 msec was observed in 611 neonates (1.4%). A QTc ≥ 470 ms was found in 31 neonates (0.07%). Genetic analysis was performed in 28/31 (90%) neonates and LQTS mutations were identified in 14 of them (50%): 8 were LQT1, 4 LQT2 and 2 LQT3. Besides one de novo mutation, all other cases were familial and genetic analysis identified additional family members (37/72, 51%) affected by LQTS who had not been previously diagnosed. Within these 28 infants QTc was longer in the positively genotyped neonates (493±22 vs 479±6 ms, p=0.037) and a LQTS mutation was identified in all the neonates (n=5) with a QTc > 496 ms. Conclusions. An ECG performed in the first month of life, with genetic analysis in selected cases, allows early diagnosis of infants with sporadic and familial forms of LQTS, thus leading to institution of effective therapies aimed at preventing sudden death either in infancy or later on in life, not only in the neonates but also in their affected family members. This study also provides a first data-based estimate of LQTS prevalence, likely to be between 1/3,000 and 1/2,500 live births.

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Response of the QT interval to mental and physical stress in types LQT1 and LQT2 of the long QT syndrome

Heart ◽

10.1136/hrt.86.1.39 ◽

2001 ◽

Vol 86 (1) ◽

pp. 39-44

Author(s):

K J Paavonen ◽

H Swan ◽

K Piippo ◽

L Hokkanen ◽

P Laitinen ◽

...

Keyword(s):

Heart Rate ◽

Serum Potassium ◽

Long Qt Syndrome ◽

Qt Interval ◽

Mental Stress ◽

Physical Stress ◽

Exercise Stress ◽

Long Qt ◽

Qt Intervals ◽

Qt Syndrome

OBJECTIVETo study and compare the effects of mental and physical stress on long QT syndrome (LQTS) patients.DESIGNCase–control study.MAIN OUTCOME MEASURESQT intervals were measured from lead V3. Serum potassium and plasma catecholamine concentrations were also monitored.PATIENTS16 patients with type 1 LQTS (LQT1), 14 with type 2 LQTS (LQT2), both groups asymptomatic, and 14 healthy control subjects.INTERVENTIONSThree types of mental stress tests and a submaximal exercise stress test.RESULTSHeart rate responses to mental stress and exercise were similar in all groups. During mental stress, the mean QT interval shortened to a similar extent in controls (–29 ms), LQT1 patients (–34 ms), and LQT2 patients (–30 ms). During exercise, the corresponding QT adaptation to exercise stress was more pronounced (p < 0.01) in healthy controls (–47 ms) than in LQT1 (–38 ms) or LQT2 patients (–38 ms). During exercise changes in serum potassium concentrations were correlated to changes in QT intervals in controls, but not in LQTS patients. LQT1 and LQT2 patients did not differ in serum potassium, catecholamine or heart rate responses to mental or physical stress.CONCLUSIONSQT adaptation to mental and exercise stress in healthy people and in patients with LQTS is different. In healthy people QT adaptation is more sensitive to physical than to mental stress while no such diverging pattern was seen in asymptomatic LQTS patients.

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