A different background of arrhythmia in siblings with a positive family history of sudden death at young age

We present two symptomatic sisters who had a positive family history of sudden death. None of them had structural heart disease. In the 25‐year‐old proband, complex ventricular arrhythmia, cardiac conduction system disease, and skeletal muscle weakness were found. Genetic examination showed a pathogenic intronic variant in the desmin gene in the proband only. In the elder sister with palpitations, complex ventricular arrhythmia (>46 000 ectopic beats) was removed by radiofrequency ablation. This family case shows that complex ventricular arrhythmia may have different background within one family, genetic examinations should be performed in a person with broadest spectrum of symptoms.     

QT interval prolongation and sudden cardiac death in diabetic autonomic neuropathy

Alterations in cardiac sympathetic innervation may result in QT interval prolongation and predispose to sudden arrhythmias and death. Sudden cardiac death occurs in diabetic patients who have autonomic neuropathy, but the cause is uncertain. In 30 patients with insulin-dependent diabetes mellitus who had no evidence of ischemic heart disease, cardiac autonomic neuropathy, determined by clinical tests, was found in 17. The corrected QT interval (QTc), measured using Bazett's formula at rest and peak exercise, was prolonged (greater than 440 msec) in 12 of these patients at rest and in 15 at peak exercise. Prolonged QTc intervals were found only in patients who had definite cardiac autonomic neuropathy. As a group, the QTc interval (mean +/- SD) in the diabetic patients with cardiac autonomic neuropathy was prolonged compared to that in patients without cardiac autonomic neuropathy at rest (447 +/- 28 vs. 405 +/- 9 ms; P less than 0.0001) and peak exercise (468 +/- 23 vs. 402 +/- 23 ms; P less than 0.0001). There was a direct linear relationship between the extent of cardiac autonomic neuropathy and the QTc interval (r = 0.71; P less than 0.001). One of the patients with cardiac autonomic neuropathy and prolonged QTc intervals had a nonuniform loss of adrenergic neurons in his heart demonstrated by meta-iodobenzyl-guanidine scintigraphy, indicating sympathetic imbalance; he subsequently died unexpectedly. These data suggest that diabetic cardiac autonomic neuropathy may result in sympathetic imbalance and QTc interval prolongation, predisposing these patients to sudden arrhythmias and death.     

Familial long QT interval and sudden death (author's transl)

A family in whom two brothers, a sister and the father presented a long QT interval is reported. The father died suddenly at the age of 37. The opportunity of a more careful research of the syndrome, now underdiagnosed, is underlined in view of the curability such disease.     

QT间期动态性在扩张型心肌病猝死风险预测中的价值

目的 研究QT间期频率依赖性在原发性扩张型心肌病(扩心病)患者猝死风险预测中的作用.方法 选取55例原发性扩心病患者和27例健康志愿者(对照组).询问病史并行心脏超声、心电图和动态心电图检查.检测左室舒张末期内径(LVEDD)、左室射血分数(LVEF)、QT间期离散度(QTd)、心率变异性(SDNN)、QT/RR相关直线的斜率、24 h室性早搏(VPB)和非持续性室性心动过速(NSVT)的次数.随访扩心病患者,随访终点为全因死亡.结果 扩心病组的LVEDD、QTd、VPB、NSVT、QTe/RR(QTe为Q波起始至T波终点的间期)和QTp/RR(QTp为Q波起始至T波顶点的间期)斜率显著高于对照组;LVEF和SDNN显著低于对照组.扩心病猝死组、非猝死组和对照组相比,LVEDD、LVEF、QTd、SDNN、QTe/RR和QTp/RR斜率的差异有统计学意义.扩心病猝死组和非猝死组比较,LVEF、SDNN、QTe/RR和QTp/RR斜率的差异有统计学意义.扩心病NSVT阳性组和NSVT阴性组比较,LVEF、QTd、VPB、QTe/RR和QTp/RR斜率的差异有统计学意义.扩心病患者的猝死率,QTe/RR斜率≥0.210者显著高于＜0.210者(54.5%与21.1%,P＜0.05);QTp/RR斜率≥0.190者显著高于＜0.190者(52.2%与21.9%,P＜0.05);在LVEF≤35%和NSVT阳性的基础上结合应用QTe/RR≥0.210或QTp/RR≥0.190,猝死率显著提高.结论 扩心病猝死组QT/RR斜率显著高于非猝死组和对照组,QT频率依赖性对扩心病患者猝死有较高的预测价值,并可进一步提高NSVT和LVEF的预测价值.     

Conduction system findings in sudden death in young adults with a history of bronchial asthma

Objectives. This study was conducted to determine whether there are any pathologic changes in the conduction system when death occurs suddenly in young adults with a history of bronchial asthma.Background. There is a worldwide increase in sudden death, especially in young adults with a history of bronchial asthma.Methods. We studied the conduction system by serial section examination in six male patients (16 to 23 years old) with a history of bronchial asthma who died suddenly.Results. The sinoatrial node artery was narrowed in two patients, with chronic inflammatory cells in three; it was fibrosed in one. The atrioventricular (AV) node was within the central fibrous body in three patients and isolated by fat in one. The AV bundle was markedly fragmented in five patients and fibrosed in two. The right and left bundle branches showed fat, fibrosis and disruption in five patients. Increased fibrosis on the summit of the ventricular septum with patchy fibrosis was present in five patients, and inflammatory cells in the conduction system were found in one.Conclusions. 1) There are distinct pathologic findings in the conduction system of young adults with a history of bronchial asthma who die suddenly. 2) The significant findings appear to be a markedly fragmented bundle and changes in the sinoatrial node that are not found in normal healthy young adults. 3) The changes in the conduction system may create an arrhythmic event, and sudden death may occur in some persons during an altered physiologic state. 4) We hypothesize that bronchial asthma may be associated with an alteration in immune complexes that affects the conduction system in some patients.     

Postmortem long QT syndrome genetic testing for sudden unexplained death in the young.

OBJECTIVES: This study sought to determine the spectrum and prevalence of long QT syndrome (LQTS)-associated mutations in a large cohort of autopsy-negative sudden unexplained death (SUD). BACKGROUND: Potentially heritable arrhythmia syndromes may explain a significant proportion of SUD in the young. Here, comprehensive postmortem LQTS genetic testing was performed in a cohort of SUD cases. METHODS: From September 1998 to March 2004, 49 cases of SUD (30 male patients, average age at death 14.2 +/- 10.9 years) were referred by medical examiners/coroners to Mayo Clinic's Sudden Death Genomics Laboratory. Using polymerase chain reaction, denaturing high-performance liquid chromatography, and direct DNA sequencing, open reading frame/splice site mutational analysis was conducted for all 8 genes implicated in the pathogenesis of either LQTS (LQT1 to LQT6) or multisystem disorders involving either QT or QU prolongation. RESULTS: Ten LQTS-associated mutations (4 novel) were discovered in 10 SUD cases (20%, 8 female patients, average age at death 18.0 +/- 11.8 years). The LQTS susceptibility mutations LQT1 (5), LQT2 (3), and LQT3 (2) were far more common among women (8 of 18, 44%) than men (2 of 30, 6.7%, p < 0.008). The activities at the time of SUD included sleep (5), exertion (2), auditory arousal (1), and undetermined (2). Sudden death was the sentinel event in two-thirds of the cases. CONCLUSIONS: In this cardiac channel-focused molecular autopsy investigation of SUD, over one-third of decedents harbored a putative cardiac channel mutation: 7 previously reported to host mutations in the RyR2-encoded calcium release channel and now 10 with LQTS susceptibility mutations. Accordingly, postmortem cardiac channel genetic testing should be pursued in the evaluation of autopsy-negative SUD.     

QT离散度与冠心病猝死

目的 :探讨 QTd对猝死的预测价值。方法 :分析 2 3例发生猝死的冠心病患者和 34例住院冠心病患者的 QT离散度及心率校正 QT离散度。结果 :猝死组 QTd明显高于对照组 ,P<0 .0 5。结论 :QT离散度增大有预测猝死的价值     

Contribution of heart rate to QT interval shortening during exercise

The contributions of the intrinsic effect of heart rate andfactors other than heart rate, to exercise-induced QT intervalshortening were assessed by studying a group of 24 patientswith implanted, programmable P wave synchronised pacemakersand a group of 10 patients undergoing atrial and ventricularpacing at rest. In each patient with an implanted pacemaker, the relation betweenatrial rate and QT interval was studied during exercise in bothatrial synchronised and asynchronous (fixed-rate) ventricularpacing modes. In three patients the exercise tests were repeatedafter beta-adrenergic blockade. There was a close linear correlation between atrial rate andQT interval reduction in each exercise test. With asynchronousventricular pacing, QT shortening did occur but to a lesserextent than during atrial synchronised pacing and could be abolishedby beta-adrenergic blockade. When the heart rate was increased at rest by either atrial orventricular pacing QT interval shortening did occur but againto a lesser degree than with atrial synchronised ventricularpacing during exercise. The results suggest that the heart rate is only one of the determinantsof the QT interval duration, and other factors, presumably associatedwith sympathetic activity, also contribute to QT interval shorteningduring exercise. By comparing the QT interval changes duringatrial synchronised and asynchronous ventricular pacing on awithin-patient basis, we determined that the contribution ofthe intrinsic effect of heart rate to QT interval shorteningduring exercise varied from 26 to 75%.     

Documented sudden cardiac death in prolonged QT syndrome

Documentation of the mechanism of sudden death is described in a patient with a prolonged QT interval. Ventricular tachycardia was initiated by a ventricular premature beat (VPB) with a prematurity index similar to previous isolated VPBs. This event occurred despite the fact that the patient was receiving phenytoin sodium, a drug known to shorten the QT interval.     

Prolonged QT interval in neonates: benign, transient, or prolonged risk of sudden death.

To determine the factors relating to prognosis, the records of 15 neonates with persistent prolongation of the QT interval on the electrocardiogram after the fourth day of life were reviewed. Patients were admitted for symptoms (syncope, cardiac failure, or seizures), abnormal auscultation with an irregular heart rate or bradycardia, or because of a family history of a long QT syndrome. All infants had a long QTc, ranging from 0.46 to more than 0.70 second. Eight patients who had a QTc over 0.60 second developed severe ventricular arrhythmias (torsades de pointes, ventricular tachycardia) or second-degree AV block. Twelve of 15 were treated with beta-blocking agents, combined with ventricular pacing in five cases. Four infants died in the first month of life; they all had a very long QT interval and had experienced ventricular arrhythmias and AV block. Six children are still being treated with beta-blocking agents for the long QT syndrome and are doing well. In five infants, electrocardiographic abnormalities were transient and the QT interval returned to normal within 1 year. Therefore (1) prolongation of the QT interval in neonates may be transient or may represent an early form of the long QT syndrome and (2) the length of the QT interval may provide data on prognosis: those with a QTc less than 0.50 second returned to normal; those with a QTc greater than 0.60 second were associated with severe arrhythmias and four of eight infants died.     

QT interval variables from 24 hour electrocardiography and the two year risk of sudden death.

OBJECTIVE--To study the effects of variability in the duration of the QT interval corrected for heart rate (QTc) on the occurrence of sudden death. DESIGN--Nested case-referent study. SUBJECTS--Cohort of 6693 consecutive patients who underwent 24 hour electrocardiography and were followed up for two years. Risk implications of QTc interval variables were studied in patients without evidence of cardiac dysfunction or of an intraventricular conduction defect (104 died suddenly and 201 patients were randomly drawn from the study cohort). MAIN OUTCOME MEASURES--Mean QTc interval duration and variation in QTc duration over time correlated with occurrence of sudden death. RESULTS--Patients with a prolonged mean QTc over 24 hours (> or = 440 ms) had a 2.3 times (95% confidence interval 1.3 to 4.5) higher risk of dying suddenly than patients with a normal mean QTc (400-440 ms); patients with a shortened mean QTc (< 400 ms) also had a higher risk (relative risk 2.4 (1.4 to 4.3)). Patients with low (< 20 ms) and high (> or = 25 ms) long term variation in QTc duration had an increased risk of dying suddenly compared with those with intermediate variation (20-25 ms) (relative risks 2.2 (1.2 to 4.2) and 2.3 (1.4 to 4.2) respectively). The relative risks for low and high short term variation were not significantly raised. CONCLUSIONS--A prolonged and a shortened mean QTc interval over 24 hours was associated with a more than twofold risk of sudden death compared with intermediate mean QTc values (400-440 ms). Neither short nor long term variability in QTc had a distinct relation with the risk of sudden death.     

Myocardial bridging in a young patient with sudden death

Systolic compression of a coronary artery is considered to be a benign phenomenon, although numerous case reports have suggested an association between bridging and sudden death or ischemia in certain patients without other abnormalities on cardiovascular evaluation. We present the case of a young patient with two episodes of spontaneous ventricular fibrillation and electrocardiographic evidence of ischemia, whose only primary abnormality on extensive workup was a long segment of left anterior descending systolic compression. This case adds to the growing body of anecdotal evidence that myocardial bridging may be associated with significant cardiac events.