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.     

Comparison of formulae for heart rate correction of QT interval in exercise ECGs from healthy children

OBJECTIVE—To investigate the differences in four formulae for heart rate correction of the QT interval in serial ECG recordings in healthy children undergoing a graded exercise test.
SUBJECTS—54 healthy children, median age 9.9 years (range 5.05-14.9 years), subjected to graded physical exercise (on a bicycle ergometer or treadmill) until heart rate reached > 85% of expected maximum for age.
DESIGN—ECG was recorded at baseline, at maximum exercise, and at one, two, four, and six minutes after exercise. For each stage, a 12 lead digital ECG was obtained and printed. In each ECG, QT and RR interval were measured (lead II), heart rate was calculated, and QTc values were obtained using the Bazett, Hodges, Fridericia, and Framingham formulae. A paired t test was used for comparison of QTc, QT, and RR interval at rest and peak exercise, and analysis of variance for all parameters for different stages for each formula.
RESULTS—From peak exercise to two minutes recovery there was a delay in QT lengthening compared with RR lengthening, accounting for differences observed with the formulae after peak exercise. At peak exercise, the Bazett and Hodges formulae led to prolongation of QTc intervals (p < 0.001), while the Fridericia and Framingham formulae led to shortening of QTc intervals (p < 0.001) until four minutes of recovery. The Bazett QTc shortened significantly at one minute after peak exercise.
CONCLUSIONS—The practical meaning of QT interval measurements depends on the correction formula used. In studies investigating repolarisation changes (for example, in the long QT syndromes, congenital heart defects, or in the evaluation of new drugs), the use of an ad hoc selected heart rate correction formula may bias the results in either direction. The Fridericia and Framingham QTc values at one minute recovery from exercise may be useful in the assessment of long QT syndromes.


Keywords: paediatric exercise testing; QT interval; QTc formulae     

Jervell-Lange Nielsen syndrome in a family with the long QT syndrome (LQTS)

A child with Jervell-Lange Nielsen syndrome is presented from Kolkata. Family study showed that the other family members are suffering from long QT syndrome. The child had frequent syncopal attack and very prolonged QT interval requiring left cardiac sympathetic denervation and beta-blocker therapy as patient could not afford implantable defibrillator and cardiac pacing.     

帕金森病与QTc间期的关系

目的：观察帕金森病（PD）与QTc间期的关系。方法：分析了37例PD患者及37例健康对照组的QTc间期,并比较PD病病情与QTc间期的关系,结果：PD组QTc间期明显超过对照组（P＝0．001）,PD病情的轻重可影响QTc间期。结论：对QTc间期的监测有助于发现PD患者自主神经功能障碍,同时可作了为解病情轻重的一个参考指标。     

心率变异及QTc间期与2型糖尿病慢性并发症的相关分析

目的观测2型糖尿病有、无慢性并发症及其心率变异（HRV）、QTc间期的变化。方法2型糖尿病患者79例,根据临床检查区分各并发症,分为无并发症组（I组17例）、冠心病组（Ⅱ组17例）、糖尿病肾病组（Ⅲ组15例）、糖尿病周围神经病变组（IV组17例）及多种并发症组（V组13例）进行24h动态心电图HRV分析及标准12导联心电图记录QTc间期。结果①2型糖尿病慢性并发症组QTe均〉0．44S,且以冠心病组最为显效,但各组间比较差异无统计学意义（P〉0．05）。②2型糖尿病慢性并发症组其HRV时域及频域指标明显低于无并发症组（P〉0,01）。结论2型糖尿病各种慢性并发症组其QTc间期延长、HRV下降,尤其在冠心病组中更为显著,提示该组存在潜在的高猝死风险。     

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。