Mechanically induced sudden death in chest wall impact (commotio cordis)

Sudden death due to nonpenetrating chest wall impact in the absence of injury to the ribs, sternum and heart is known as commotio cordis. Although once thought rare, an increasing number of these events have been reported. Indeed, a significant percentage of deaths on the athletic field are due to chest wall impact. Commotio cordis is most frequently observed in young individuals (age 4–18 years), but may also occur in adults. Sudden death is instantaneous or preceded by several seconds of lightheadedness after the chest wall blow. Victims are most often found in ventricular fibrillation, and successful resuscitation is more difficult than expected given the young age, excellent health of the victims, and the absence of structural heart disease. Autopsy examination is notable for the lack of any significant cardiac or thoracic abnormalities.

In an experimental model of commotio cordis utilizing anesthetized juvenile swine, ventricular fibrillation can be produced by a 30 mph baseball strike if the strike occurred during the vulnerable period of repolarization, on the upslope of the T-wave. Energy of the impact object was also found to be a critical variable with 40 mph baseballs more likely to cause ventricular fibrillation than velocities less or greater than 40 mph. In addition, more rigid impact objects and blows directly over the center of the chest were more likely to cause ventricular fibrillation. Peak left ventricular pressure generated by the chest wall blow correlated with the risk of ventricular fibrillation. Activation of the K⁺_ATP channel is a likely cause of the ventricular fibrillation produced by chest wall blows. Successful resuscitation is attainable with early defibrillation.     

Soft tissue impact characterisation kit (STICK) for ex situ investigation of heart rhythm responses to acute mechanical stimulation

Both mechanical induction and mechanical termination of arrhythmias have been reported in man. Examples include pre-cordial impacts by sports implements (baseballs, pucks) that can trigger arrhythmias, including ventricular fibrillation, or via the so-called pre-cordial thump, used as an emergency resuscitation measure to convert arrhythmias to normal sinus node rhythm. These interventions have been partially reproduced in experimental studies on whole animals. Relating observations at the system's level to underlying mechanisms has been difficult, however, largely because of: (i) a deficit in efficient and affordable pharmacological agents to selectively target (sub-)cellular responses in whole animal studies, and (ii) the lack of suitable experimental models to study the above responses at intermediate levels of functional and structural integration, such as the isolated heart or cardiac tissue. This paper presents a soft tissue impact characterisation kit (STICK), suitable for quantitative investigations into the effects of acute mechanical stimulation on cardiac electro-mechanical function in rodent isolated heart or tissue preparations. The STICK offers independent control over a range of relevant biophysical parameters, such as impact location and energy, pre-impact projectile speed and contact area, as well as over the timing of a mechanical stimulus relative to the cardiac cycle (monitored via electrocardiogram, ECG, here recorded directly from the cardiac surface). Projectile deceleration upon interaction with the tissue is monitored, contact-free, with a resolution of 175 μm, providing information on tissue deformation dynamics, force, pressure and work of the mechanical intervention. In order to study functional effects of cardiac mechanical stimulation in the absence of tissue damage, impacts must be limited (for juvenile Guinea pig heart) to 2–2.5 mJ in the slack left ventricle (diastolic impact) and 5–10 mJ in contracture (systolic impact), as confirmed by enzyme assay and histological investigation. Impacts, timed to coincide with the early T-wave of the ECG, are capable of triggering short runs of ventricular fibrillation. Thus, the STICK is a suitable tool for the study of acute cardiac mechano-electric feedback effects, caused by short impulse-like mechanical stimulation, at the level of the isolated organ or tissue.     

A case report of ectopia cordis and omphalocele

A rare congenital defect in fusion of the anterior chest wall resulting in an extrathoracic location of the heart. Cantrell''s pentalogy is a congenital anomaly resulting from embryologic development defect and consists of the following: A deficiency of the anterior diaphragm, a midline supraumbilical abdominal wall defect, a defect in the diaphragmatic pericardium, congenital intracardiac abnormalities, and a defect of the lower sternum. Here we report a rare case of ectopic cordis with omphalocele.     

Repolarisation and vulnerability to re-entry in the human heart with short QT syndrome arising from KCNQ1 mutation--a simulation study

Idiopathic short QT syndrome (SQTS) is a recently identified, genetically heterogeneous condition characterised by abbreviated QT intervals and an increased susceptibility to arrhythmia and sudden death. This simulation study identifies mechanisms by which cellular electrophysiological changes in the SQT2 (slow delayed rectifier, I_Ks, -linked) SQTS variant increases arrhythmia risk. The channel kinetics of the V307L mutation of the KCNQ1 subunit of the I_Ks channel were incorporated into human ventricular action potential (AP) models and into 1D and 2D transmural tissue simulations. Incorporating the V307L mutation into simulations reproduced defining features of the SQTS: abbreviation of the QT interval, and increases in T wave amplitude and T_peak–T_end duration. In the single-cell model, the V307L mutation abbreviated ventricular cell AP duration at 90% repolarisation (APD₉₀) and increased the maximal transmural voltage heterogeneity (δV) during APs; this resulted in augmented transmural heterogeneity of APD₉₀ and of the effective refractory period (ERP). In the intact tissue model, the vulnerable window for unidirectional conduction block was also increased. In 2D tissue the V307L mutation facilitated and maintained reentrant excitation. Thus, in SQT2 increases in transmural heterogeneity of APD, δV, ERP and an increased vulnerable window for unidirectional conduction block generate an electrical substrate favourable to reentrant arrhythmia.     

Contribution of mechanical factors to arrhythmogenesis in calcium overloaded cardiomyocytes: model predictions and experiments

It is well-known that Ca²⁺ overload in cardiomyocytes may underlie arrhythmias. However, the possible contribution of mechanical factors to rhythm disturbances in Ca²⁺ overloaded myocytes has not been sufficiently investigated. We used a mathematical model of the electrical and mechanical activity of cardiomyocytes to reveal an essential role of the mechanisms of cardiac mechano-electric feedback in arrhythmogenesis in Ca²⁺ overloaded myocardium. In the model, the following mechanical factors increased Ca²⁺ overload in contracting cardiomyocytes and promoted rhythm disturbances: i) a decrease in the mechanical load for afterloaded contractions; and ii) a decrease in the initial length of sarcomeres for isometric twitches. In exact accordance with the model predictions, in experiments on papillary muscles from the right ventricle of guinea pigs with Ca²⁺ overloaded cardiomyocytes (using 0.5-1 μM of ouabain), we found that emergence of rhythm disturbances and extrasystoles depends on the mechanical conditions of muscle contraction.     

基于支持向量机的室颤信号检测算法

目的:实现室颤信号与非室颤信号的分类,进而实现室颤信号的检测。方法:本文引入了一种基于支持向量机(Support Vec-tor Machine,SVM)和改进的越限区间算法(TCI)的新算法,其中支持向量机在处理分类和模式识别等问题中具有很大的优势。该算法采用4s的滑动窗技术,并利用改进后的越限区间算法(Threshold Crossing Interval,TCI)方法提取心电信号的特征。新算法的实现如下:在每一滑动窗内采用改进的后的绝对值阈值,计算中间2s内的平均越限间隔值。并以此TCI值作为特征参数,输入一个预先设计好的二分类支持向量机中,从而实现分类。结果:成功实现了室颤信号的检测,通过计算该方法的灵敏度、精确度、预测性和准确度且与其他方法相比较,可知此新算法总体可靠性优于其他方法。结论:该算法能够实现室颤信号的实时监测,且简单易行,易于实现,较适合实时的心电监测以及除颤仪器。     

On the formation of circulating patterns of excitation in anisotropic excitable media

We present a model of excitable media with the feature that it has a vulnerable phase during which a premature current stimulus will result in the formation of a reentrant selfsustained wave of excitation. The model exploits anisotropic coupling of identical cells, and is therefore useful as a model for the myocardium. We give rigorous verification that there is a vulnerable phase, and demonstrate numerically that permanently rotating waves are formed. Finally, it is shown that the direction of fastest propagation in myocardium is not necessarily the direction of highest safety factor, contrary to commonly accepted opinion.     

Predictors of ventricular tachyarrhythmia in high-risk myocardial infarction patients treated with primary coronary intervention

Background. We investigated the association between clinical characteristics, angiographic data and ventricular arrhythmia in patients with ST-elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (PCI) Methods. In patients with STEMI (n=225), a Holter analysis was performed the first 12 hours after primary PCI. Results. A total of 151 (66%) patients had ≥1 episode of ventricular tachycardia (VT). Age <70 years (RR 4.9, 95% CI 1.8 to 12.7), TIMI 0-1 pre-PCI (RR 2.6, 95% CI 1.1 to 6.1) and peak CK (RR 3.5, 95% CI 1.9 to 5.8) were independent predictors of VT. One-year mortality was 7%, no association between mortality and presence of early VT was found. Conclusion. Ventricular tachycardia is common in the first 12 hours after primary PCI for STEMI. Independent predictors of VT are younger age, TIMI 0-1 flow prior to PCI and larger infarct size. The presence of early VT was not significantly associated with one-year mortality. (Neth Heart J 2010;18:122-8.)     

Cardiac gene expression profiling – the quest for an atrium-specific biomarker

Biomarkers are gaining increasing interest to predict risk but also to aid in diagnostics. Tissue-specific biomarkers are of utmost importance to detect diseases of respective organs. As of yet there are no atriumspecific biomarkers for risk stratification of atrial disease, such as atrial fibrillation. Bioinformatics such as mRNA microarrays can help to detect tissue-enriched and possibly tissue-specific expressed genes that can be targets for biomarkers. We describe an approach to identify genes preferably expressed in atrial cardiomyocytes compared with ventricular cardiomyocytes by RNA microarray and confirmed by quantitative real-time polymerase chain reaction. By this approach we identified several atrium-enriched genes but also ventricle-enriched genes. As expected atrial natriuretic peptide (ANP) mRNA showed higher expression in atrial cardiomyocytes while with adrenergic stimulation expression was almost as high in ventricular as in atrial cells. Brain-type natriuretic peptide (BNP), however, was not different between atrial and ventricular cells giving a possible explanation for increased levels of NT-proBNP in atrial fibrillation patients. Interesting identified candidates are serpine1 and ltbp2 as atrium-enriched genes whereas alpha-adrenergic receptor subtype 1b and S100A1 expression was significantly higher in ventricular cells. The identified genes need to be confirmed in human tissue and might ultimately be tested as potential biomarkers for atrial stress. (Neth Heart J 2010;18:610–4.)     

Epidemiology of sudden cardiac death in rural South India - insights from the andhra pradesh rural health initiative

Background

Sudden cardiac death (SCD) is a common initial presentation of coronary artery disease (CAD). Despite the growing epidemic of CAD in India, the epidemiology of SCD is largely unknown.

Objective

The objective of the study was to define the prevalence and determinants of sudden cardiac deaths in rural South India.

Methods

Prospective mortality surveillance was conducted in 45 villages (180,162 subjects) in rural South India between January 2006 and October 2007. Trained multipurpose health workers sought to do verbal autopsies within 4 weeks of any death. Detailed questionnaires including comorbidities and circumstances surrounding death were recorded. SCD was adjudicated using the modified Hinkle-Thaler classification.

Results

A total of 1916 deaths occurred in the study population over the 22 month time period and verbal autopsy was obtained in 1827 (95%) subjects. Overall mean age of the deceased was 62 ± 20 years and 1007 (55%) were men. Cardiovascular and cerebrovascular diseases together accounted for 559 deaths (31%), followed by infectious disease (163 deaths, 9%), cancer (126 deaths, 7%) and suicide (93 deaths, 5%).Of the 1827 deaths, after excluding accidental deaths (89 deaths), 309 deaths (17%) met criteria for SCD. Cardiovascular disease was the underlying causes in the majority of the SCD events (231/309 (75%)). On multivariate analyses, previous MI/CAD (p < 0.001, OR 14.25), hypertension (p < 0.001, OR 1.84), and age groups between 40-60 yrs (p=0.029) were significantly associated with SCD.

Conclusion

Sudden cardiac death accounted for up to half of the cardiovascular deaths in rural Southern India. Traditional cardiovascular risk factors were strongly associated with SCD.     

心源性猝死心电预测和综合防治研究进展

随着社会老龄化的进一步加剧,冠心痛、高血压、心肌病、恶性心律失常的发病率也成为导致人群中猝死率上升的重要诱发因素.对猝死发病机制的研究中,室性心动过速和室颤往往是导致病人发生猝死的最主要的终末事件.在这篇文章中我们通过12导联心电图(ECG)的心电学预测因子的研究,揭示心电学预测因子在预防心源性猝死中的临床应用价值.另一方面,如何能提高预防猝死的预测因子的敏感性和特异性,发现新的更有临床应用价值的心电学预测因子,更好的防治猝死对社会人群的危害,成为临床研究中不断探寻的答案.最后,我们将近年来对心源性猝死的防治措施及未来的发展方向做一简要的综述.     

Identification of loss-of-function RyR2 mutations associated with idiopathic ventricular fibrillation and sudden death

Mutations in cardiac ryanodine receptor (RyR2) are linked to catecholaminergic polymorphic ventricular tachycardia (CPVT). Most CPVT RyR2 mutations characterized are gain-of-function (GOF), indicating enhanced RyR2 function as a major cause of CPVT. Loss-of-function (LOF) RyR2 mutations have also been identified and are linked to a distinct entity of cardiac arrhythmia termed RyR2 Ca²⁺ release deficiency syndrome (CRDS). Exercise stress testing (EST) is routinely used to diagnose CPVT, but it is ineffective for CRDS. There is currently no effective diagnostic tool for CRDS in humans. An alternative strategy to assess the risk for CRDS is to directly determine the functional impact of the associated RyR2 mutations. To this end, we have functionally screened 18 RyR2 mutations that are associated with idiopathic ventricular fibrillation (IVF) or sudden death. We found two additional RyR2 LOF mutations E4146K and G4935R. The E4146K mutation markedly suppressed caffeine activation of RyR2 and abolished store overload induced Ca²⁺ release (SOICR) in human embryonic kidney 293 (HEK293) cells. E4146K also severely reduced cytosolic Ca²⁺ activation and abolished luminal Ca²⁺ activation of single RyR2 channels. The G4935R mutation completely abolished caffeine activation of and [³H]ryanodine binding to RyR2. Co-expression studies showed that the G4935R mutation exerted dominant negative impact on the RyR2 wildtype (WT) channel. Interestingly, the RyR2-G4935R mutant carrier had a negative EST, and the E4146K carrier had a family history of sudden death during sleep, which are different from phenotypes of typical CPVT. Thus, our data further support the link between RyR2 LOF and a new entity of cardiac arrhythmias distinct from CPVT.     

A novel locus for dilated cardiomyopathy maps to canine chromosome 8

Dilated cardiomyopathy (DCM), the most common form of cardiomyopathy, often leads to heart failure and sudden death. While a substantial proportion of DCMs are inherited, mutations responsible for the majority of DCMs remain unidentified. A genome-wide linkage study was performed to identify the locus responsible for an autosomal recessive inherited form of juvenile DCM (JDCM) in Portuguese water dogs using 16 families segregating the disease. Results link the JDCM locus to canine chromosome 8 with two-point and multipoint lod scores of 10.8 and 14, respectively. The locus maps to a 3.9-Mb region, with complete syntenic homology to human chromosome 14, that contains no genes or loci known to be involved in the development of any type of cardiomyopathy. This discovery of a DCM locus with a previously unknown etiology will provide a new gene to examine in human DCM patients and a model for testing therapeutic approaches for heart failure.     

Cardiac Arrhythmias In Congenital Heart Diseases

Arrhythmias figure prominently among the complications encountered in the varied and diverse population of patients with congenital heart disease, and are the leading cause of morbidity and mortality. The incidence generally increases as the patient ages, with multifactorial predisposing features that may include congenitally malformed or displaced conduction systems, altered hemodynamics, mechanical or hypoxic stress, and residual or postoperative sequelae. The safe and effective management of arrhythmias in congenital heart disease requires a thorough appreciation for conduction system variants, arrhythmia mechanisms, underlying anatomy, and associated physiology. We, therefore, begin this review by presenting the scope of the problem, outlining therapeutic options, and summarizing congenital heart disease-related conduction system anomalies associated with disorders of the sinus node and AV conduction system. Arrhythmias encountered in common forms of congenital heart disease are subsequently discussed. In so doing, we touch upon issues related to risk stratification for sudden death, implantable cardiac devices, catheter ablation, and adjuvant surgical therapy.     

Sleep Biological Rhythms in Normal Infants and those at High Risk for SIDS

The focus of this study was on daytime and nighttime sleep and wakefulness during the peak age for Sudden Infant Death Syndrome (SIDS), two to four months, to determine whether there are differences between at‐risk for SIDS (R) and control (C) infants. Such differences may provide insight on the frequent occurrence of SIDS in the early morning hours, when most babies are asleep. This is the only study in which R and C infants were continuously monitored for long periods of time (24–48 h) and then followed and recorded at monthly intervals until the age of 4–6 months. Data analyses indicate that ultradian REM/NREM cyclicity becomes stabilized into a regular pattern at three months of age. Infants at this age convert from a polyphasic sleep/wakefulness pattern to a circadian one. Among the changes that occur is a lengthening of short sleep periods that consolidate at night and wake periods that consolidate in the daytime. The most striking effects are related to sleep state and vary according to age and sex. The lengthening of single sleep and wakeful periods is coupled with the maturation of the brain. The development of the central nervous system facilitates the synchronization of sleeping patterns with external light input and social entrainment. One or more biological clocks or oscillators may be responsible for these REM/NREM patterns and circadian cycles. These differences during the early morning hours, when the occurrence of SIDS peaks, may have important implications for understanding the pathophysiological mechanism of SIDS.     

Sleep biological rhythms in normal infants and those at high risk for SIDS

The focus of this study was on daytime and nighttime sleep and wakefulness during the peak age for Sudden Infant Death Syndrome (SIDS), two to four months, to determine whether there are differences between at-risk for SIDS (R) and control (C) infants. Such differences may provide insight on the frequent occurrence of SIDS in the early morning hours, when most babies are asleep. This is the only study in which R and C infants were continuously monitored for long periods of time (24-48 h) and then followed and recorded at monthly intervals until the age of 4-6 months. Data analyses indicate that ultradian REM/NREM cyclicity becomes stabilized into a regular pattern at three months of age. Infants at this age convert from a polyphasic sleep/wakefulness pattern to a circadian one. Among the changes that occur is a lengthening of short sleep periods that consolidate at night and wake periods that consolidate in the daytime. The most striking effects are related to sleep state and vary according to age and sex. The lengthening of single sleep and wakeful periods is coupled with the maturation of the brain. The development of the central nervous system facilitates the synchronization of sleeping patterns with external light input and social entrainment. One or more biological clocks or oscillators may be responsible for these REM/NREM patterns and circadian cycles. These differences during the early morning hours, when the occurrence of SIDS peaks, may have important implications for understanding the pathophysiological mechanism of SIDS.     

Genetic predisposition for sudden cardiac death in myocardial ischaemia: the Arrhythmia Genetics in the NEtherlandS study

Sudden cardiac death from ventricular fibrillation during myocardial infarction is a leading cause of total and cardiovascular mortality. This multifactorial, complex condition clusters in families, suggesting a substantial genetic cause. We carried out a genomewide association study (GWAS) for sudden cardiac death, in the AGNES (Arrhythmia Genetics in the Netherlands) population, consisting of patients with (cases) and without (controls) ventricular fibrillation during a first ST-elevation myocardial infarction. The most significant association was found at chromosome 21q21 (rs2824292; odds ratio = 1.78, 95% CI 1.47–2.13, P = 3.3 × 10⁻¹⁰), 98 kb proximal of the CXADR gene, encoding the Coxsackie and adenovirus receptor. This locus has not previously been implicated in arrhythmia susceptibility. Further research on the mechanism of this locus will ultimately provide novel insight into arrhythmia mechanisms in this condition.     

The meaning of character combination for the separation of EEG-data

Summary Standard EEG risk evaluation works on scoring systems that use different types of questionnaires. Here, an alternative for SIDS (Sudden Infant Death Syndrome) risk detection is presented that is based exclusively on EEG data which possibly could substitute the procedure of questioning the parents and allow a direct qualification of the physiological disposition of the individual neonate: Using EEG-characters an approved SIDS-case could be discriminated as well against the group of “healthy” infants as against the “high-risk-group”. The results of this study may confirm the evidence that the EEG analysis can be a promising approach to predict an increased SIDS risk.