hypothermia therapy for a survivor of CA due to drug- induced LQTs [4]. Here, we report the efficacy of therapeutic hypothermia for 2 patients with congenital LQTs.

A 27-year-old man was resuscitated from CA. The automated external defibrillator detected and terminated ventricular fibrillation. He had a previous history of syncope 8 years earlier, although he had not undergone any clinical examinations. In the emergency department (ED), TdP was induced and terminated spontaneously (body temperature, 36.9?C; Fig. 1A). A 12-lead electrocar- diography (ECG) showed that his longest QT interval (QT) was 360 milliseconds, and his longest QT interval corrected by Bazett formula (QTc) was 499 milliseconds on admission (Fig. 1B). Late-onset T waves were apparent in the inferior, V₄, and V₅ leads. The patient was not taking any medicines that could prolong the QT interval. His serum potassium (4.2 mEq/L), magnesium (2.3 mEq/L), and troponin T levels were within normal limits. Subarach- noid hemorrhage was not detected by the computed tomographic scan. He remained with a Glasgow Coma Scale score of 6 after his hemodynamic status had stabilized; his blood pressure was 114/60 mm Hg, and heart rate was 110 beats per minute. The Mild hypothermia therapy was started with cooling blankets at a maximal rate of about 1.0?C per hour. The QTc increased to 667 milliseconds at the target temperature of 33.8?C (Fig. 1C). However, TdP did not recur during therapeutic hypother- mia. The prophylactic administration of Antiarrhythmic drugs and ventricular pacing were not performed. Two days after admission, the rewarming at a rate of 0.2?C per hour was started. Although the patient’s temperature was being elevated, QT intervals gradually shortened but remained prolonged. The withdrawal of sedative drug was not pursued while QT prolongation remained. Three days after completion of rewarming, QTc shortening reached a plateau at 500 milliseconds (36.6?C; Fig. 1D); and then, he was extubated. A cardiac echocardiogram showed no structural heart disease and normal left ventricular function. The coved type of ST-segment elevation (N0.2 mV) was apparent in the right precordial lead after administration of the sodium-channel blocker (pilsicainide 1 mg/kg). DNA sequencing of the patient revealed E1784K (G5350A) mutation in the SCN5A gene. His twin sister carried the same mutation. He was diagnosed with LQTs type 3 and Brugada syndrome (overlap syndrome).

0735-6757/$ – see front matter (C) 2012

Fig. 1 A survivor of sudden cardiac arrest due to LQTs type 3 and Brugada syndrome. A, Torsade de pointes was induced after a long pause (body temperature, 36.9?C). B, On admission, the QT and QTc intervals were 360 and 499 milliseconds, respectively (36.9?C). C, During therapeutic hypothermia (33.8?C), QT and QTc increased to 640 and 667 milliseconds. D, Three days after completion of rewarming, QT and QTc shortening reached a plateau at 400 and 500 milliseconds, respectively (36.6?C). Note that TdP did not recur during therapeutic

Fig. 2 The other survivor with LQTs type 1. A, On admission, QT and QTc were 440 and 534 milliseconds, respectively (36.4?C). B, During therapeutic hypothermia (34.3?C), QT and QTc were 520 and 626 milliseconds, respectively. C, Two days after completion of rewarming, QT and QTc decreased to 480 and 500 milliseconds, respectively (36.5?C). Torsade de pointes did not recur during therapeutic

A 13-year-old boy underwent mild hypothermia therapy after resuscitation. He had an aborted CA in his school. He had been diagnosed with LQTs 4 years earlier, although he had not undergone genetic testing. He had been taking 40 mg of metoprolol twice a day since then. During gymnastics, he suddenly collapsed. Ventricular fibrillation was terminated by Direct current shock, and spontaneous circulation was restored 28 minutes after CA. On admission, ECG showed QTc prolongation of 534 milliseconds with broad and pronounced T waves (36.4?C, Fig. 2A). His serum potassium (4.2 mEq/L), magnesium (3.2 mEq/L), and troponin T levels were within normal limits. The computed tomographic scan did not detect subarachnoid hemorrhage. In the ED, no ventricular arrhythmias were recorded during ECG monitor- ing; and the patient remained comatose with a Glasgow Coma Scale score of 6, although his hemodynamic status had stabilized; his blood pressure was 112/53 mm Hg, and heart rate was 88 beats per minute. Therapeutic hypothermia was started, and ?-blocker was administered intravenously (landiolol 10 ug/kg per minute) during this treatment. The QTc was prolonged to 626 milliseconds at the target temperature of 34.3?C (Fig. 2B). Thirty-six hours later, the rewarming was started. Although the patient’s temperature was being elevated, QTc gradually shortened but remained prolonged. Two days after completion of rewarming, QTc shortening reached a plateau at 500 milliseconds (36.5?C; Fig. 2C); and the patient was extubated successfully. No ventricular tachyarrhythmia was recorded during mild hypothermia therapy. A cardiac echocardiogram showed no structural heart disease and normal left ventricular function. DNA sequencing of the patient revealed P631fs

+33X (1839delC) mutation in the KCNQ1 gene. Genetic analysis disclosed that his mother carried the same mutation. The patient was diagnosed with LQTs type 1.

Both patients were fully recovered from neurologic damage. After placement of implantable cardioverter defibrillators, they were discharged from our hospital.

Therapeutic hypothermia may not necessarily have proarrhythmic effects in survivor of LQTs. Torsade de pointes was nor recurrent in 2 survivors of CA due to congenital LQTs during this therapy, although the QT interval was extremely prolonged. During therapeutic hypothermia, there is a decrease in delayed rectifier potassium current and a change in calcium handling of cardiac myocytes [5,6]; and the QT interval is prolonged [2]. We have reported recurrent TdP during therapeutic hypo- thermia in a patient with drug-induced LQTs [4]. However, in the present report, TdP did not recur in patients with congenital LQTs, although QTc prolongation was more than 600 milliseconds. In both patients, the withdrawal of sedative drugs and extubation were not pursued before QT shortening reached to a plateau. Increased sympathetic tone could contribute to the induction of triggered activity [7]. In each patient, electrolyte abnormalities were checked fre- quently and corrected immediately. The prophylactic administration of short-acting ?-blocker may be effective

for the patients with LQTs type 1 during therapeutic hypothermia. The safety and efficacy of prophylactic administration of Na-channel blockers have not been established for patients with LQTs because the changes in drug distribution and decelerated renal and Hepatic function may change the metabolism and elimination of drugs during therapeutic hypothermia [8]. Ventricular pacing may be recommended to increase the heart rate and to shorten the QT interval.

One clinical study excluded LQTs as an indication for therapeutic hypothermia [1]. However, our report suggests that therapeutic hypothermia can be safe and effective for treating comatose survivors of CA due to congenital LQTs.

Nobuhiro Nishiyama MD Toshiaki Sato MD Yoshiyasu Aizawa MD Department of Cardiology

Keio University School of Medicine

Tokyo, Japan E-mail address: [email protected]

Satoshi Nakagawa MD

Department of Intensive Care Unit National Center for Child Health and Development

Tokyo, Japan

Hideaki Kanki MD

Department of Cardiology, Saitama City Hospital

Saitama, Japan

doi:10.1016/j.ajem.2011.02.019

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