Severe QTc prolongation under mild hypothermia treatment and incidence of arrhythmias after cardiac arrest--a prospective study in 34 survivors with continuous Holter ECG

Background

Mild hypothermia treatment (32-34 °C) in survivors after cardiac arrest (CA) is clearly recommended by the current guidelines. The effects of cooling procedure towards QT interval have not been evaluated so far outside of case series. In a prospective study 34 consecutive survivors after cardiac arrest were continuously monitored with Holter ECG over the first 48 h.

Patients and methods

A total of 34 patients were analysed and received mild therapeutic hypothermia treatment (MTH) according to the current guidelines and irrespective of the initial rhythm. At admission to hospital and in the field in case of OHCA, a 12-lead ECG was performed in all patients.

Results

During cooling the incidence of ventricular tachycardia was low (8.8%) and in none of the patients Torsade de pointes occurred. The QTc interval was within normal range at first patient contact with EMS in the field (440.00 ms; IQR 424.25-476.75; n = 17) but during hypothermia treatment the QTc interval was significantly prolonged at 33 °C after 24 h of cooling (564.47 ms; IQR 512.41-590.00; p = 0.0001; n = 34) and decreased after end of hypothermia to baseline levels (476.74 ms; 448.71-494.97; p = 0.15).

Conclusion

The QTc interval was found to be significantly prolonged during MTH treatment, and some severe prolongations >670 ms were observed, without a higher incidence of life-threatening arrhythmias, especially no Torsade des pointes were detected. However, routine and frequent ECG recording with respect to the QTc interval should become part of any hypothermia standard operation protocol and should be recommended by official guidelines.     

我院住院患者应用胺碘酮对QTc间期的影响

摘 要 目的:评估胺碘酮对住院患者QT/ QTc间期的影响及药品不良反应。方法：纳入2014年1～6月上海浦东新区公利医院心内科使用胺碘酮的住院患者共59例,记录患者一般情况和合并用药等信息,观察应用胺碘酮注射液或胺碘酮片剂后心率、QT间期、QTc间期的变化,以及在用药期间发生药品不良反应。结果：用药后患者的平均心率、QT间期和QTc间期较用药前显著减慢(P<0.01)。59例患者中,12例用药后QTc＞500 ms,5例患者用药后△QTc＞50 ms且 QTc＜500 ms。研究中,共有8例合并使用一种或多种可延长QT间期的药物,包括左氧氟沙星（4例）,阿奇霉素（3例）,氟哌噻吨美利曲辛（1例）,多潘立酮（1例）。32例应用胺碘酮注射液患者中有3例发生注射部位反应,用药中未出现与胺碘酮相关的心律失常[包括尖端扭转性室速(Tdp）]。结论：住院患者应用胺碘酮后QT间期、QTc间期均会不同程度延长,对于用药后QTc＞500 ms、△QTc＞50 ms或合并使用其他可延长QT间期药物的患者,Tdp发生风险增加,应及时调整胺碘酮用药方案并严密监测心电图,避免恶性心律失常事件的发生。     

Homocysteine enriched diet leads to prolonged QT interval and reduced left ventricular performance in telemetric monitored mice

Background and aims

Homocysteine (Hcy) is a sulfur-containing, non-protein amino acid produced in the metabolic pathway of methionine. Hyperhomocysteinemia is associated with cerebro- and cardiovascular disease in industrialized countries, mostly resulting from protein rich diet and sedentary life style. Matrix metalloproteinases are involved in cardiac remodeling, leading to degradation of intercellular junctions, cardiac connexins and basement membranes. The study was designed to investigate the relationship between Hcy, cardiac remodeling, cardiac performance, and rhythm disturbances in an animal model of hyperhomocysteinemia. We tested the hypothesis that induction of matrix metalloproteinase-2 and matrix metalloproteinase-9 leads to connexin 40, connexin 43, connexin 45 expression changes contributing to decreased cardiac performance and disturbed atrioventricular conduction.

Methods and results

Hcy was added to drinking water of male C57/BL6J mice to achieve moderate Hcy blood levels. ECG was monitored in conscious mice with a telemetric ECG device; echocardiography was used for assessment of left ventricular function. Immunoblotting was used to evaluate matrix metalloproteinase-2, matrix metalloproteinase-9, connexin 40, connexin 43, and connexin 45 expression in cardiac tissue. Animals fed Hcy showed significant prolongation of QRS, QTc, and PR intervals along with reduced left ventricular function. Western blotting showed increased expression of matrix metalloproteinase-2, matrix metalloproteinase-9 and decreased expression of connexin 40, 43, and 45.

Conclusion

Hcy has been identified as a nutritional factor contributing to cardiovascular disease. Cardiac remodeling induced by matrix metalloproteinase-2 and matrix metalloproteinase-9 and decreased expression of connexin 40, 43, and 45 appears to play a role in the pathomechanism of atrioventricular conduction delay and ventricular dilatation in hyperhomocysteinemia.     

Prevalence and Risk Factors of Prolonged QTc Interval in HIV-Infected Patients: Results of the HIV-HEART Study

Abstract

Background: Corrected QT (QTc) prolongation is predictive of cardiovascular mortality in both the general and human immunodeficiency virus (HIV) populations. Objective: As part of the HIV-HEART study, we assessed the prevalence and risk factors of a prolonged QTc interval in patients with HIV infection. Methods: In this cross-sectional cohort study, 802 unselected HIV-infected patients were included. Data were analyzed by the use of gender-specific QTc categories (men abnormal at > 440 ms and women abnormal at >460 ms). Multiple variables related to infection and treatment were collected. Results were analyzed with a multivariable model. Results: The QTc interval was found to be prolonged in 154 patients (19.8%; 95% CI 17–23). The mean (±SD) QTc in men (n = 142) presenting with a prolonged QTc interval was 456 ± 16.3 ms (range 441–548 ms).The mean (±SD) QTc in women (n = 12) presenting with a prolonged QTc interval was 479 ± 9 ms (range 465–498 ms). In the multivariable model, female gender, diabetes mellitus, and arterial hypertension were associated with prolonged QTc. There were no parameters related to HIV independently associated with QT interval prolongation. In particular, no anti-HIV drug was associated with QTc prolongation. Conclusions: Our study demonstrated that in an HIV-infected population, QTc prolongation had a high prevalence of nearly 20% compared to the general population and was possibly influenced by common factors like gender, diabetes, and arterial hypertension.     

Supra-therapeutic doses of roflumilast have no effect on cardiac repolarization in healthy subjects

Objective: This study assesses the potential of the phosphodiesterase 4 inhibitor roflumilast to affect cardiac repolarization.

Methods: In this randomized, placebo-controlled study (n = 80), 40 healthy subjects received moxifloxacin 400 mg p.o. (positive control for prolongation of QT/heart-rate corrected QT [QTc]) and another 40 received placebo. After a 1-day washout, subjects received placebo or ascending doses of roflumilast 500 (therapeutic dose), 750 or 1000 μg/day p.o., for 14, 7 and 14 days, respectively. QT intervals were measured and corrected for heart rate with a Fridericia algorithm (QTc_F). The primary endpoint was the largest mean time-matched change in QTc_F from baseline (day 1). Safety and tolerability were monitored.

Results: Moxifloxacin gave a maximum time-matched change in QTc_F versus baseline of 6.79 ms. Repeated administration of roflumilast 500 and 1000 μg resulted in maximum QTc_F changes from baseline of -3.23 and -4.81 ms, respectively, confirming the absence of any QT/QTc prolongation at therapeutic and supra-therapeutic dosing. There were no changes in other electrocardiographic variables or time intervals, and roflumilast was well tolerated.

Conclusions: Repeated administration of roflumilast at doses ≤ 1000 μg/day had no effect on cardiac repolarization or overall cardiac safety evaluations in healthy subjects.

Clinical trial registration number: ISRCTN63818313     

Changes of heart rate and QT interval at high altitude in alpinists: analysis by Holter ambulatory electrocardiogram

The purpose of this study is to record continuously electrocardiograms of alpinists during different activities practiced in mountaineering, compare heart rate and QT interval at high altitude with those at sea level, and compare alpinists with nonalpinists. Analysis was attempted on 14 alpinists (9 male, 5 female, ages 26-45) to determine changes in heart rate and QT interval using continuous ambulatory electrocardiograms recorded at sea level and high altitude. Between 1983 and 1984, 9 of 14 alpinists (6 male, 3 female) were subjected to the study at high altitude, that is, at Mt. Kangchenjunga (Himalaya), Mt. Satopanth (Himalaya), and Mt. Jitudake (Butan), 4400 to 7800 m (mean 5710 m). The following were noted: Heart rate at high altitude was significantly higher both in daytime and nighttime. The circadian rhythm of the heart rate disappeared at extremely high altitude in several alpinists. A high correlation was noted between measured QT interval (QTm) and RR interval (r = 0.81, p = 0.005). Nighttime QTm at high altitude was prolonged in comparison with that of daytime so far as the RR interval remained the same. At high altitude, the nighttime corrected QT interval (QTc) was also significantly prolonged in spite of shortened RR interval. The mechanism of QTc prolongation is not clear. Many factors may impact on the QT interval during mountaineering.