Heart Disease Arrhythmias Research Articles

Introduction to the Series on Computational Approaches to Cardiac Arrhythmias

Of all the cardiac arrhythmias seen in clinical practice, atrial fibrillation (AF) and ventricular tachycardia/fibrillation (VT/VF) are among the leading causes of morbidity and mortality in the developed world. AF is the most common sustained arrhythmia and is associated with an increased risk of stroke, heart failure, dementia, and death.1–3 In developed nations overall prevalence of AF is 0.9% and the number of people affected is projected to more than double over the next 2 decades.3,4 VT/VF is the most important immediate cause of sudden cardiac death (SCD). Incidence of SCD is estimated to be 4 to 5 million cases per year worldwide.5,6 Thus arrhythmias and SCD are among the most significant manifestations of cardiovascular diseases worldwide, but their underlying mechanisms remain elusive. Arrhythmogenic substrates may be established by ischemia, infarction, heart failure and genetic mutations, all of which may cause inflammation, extracellular matrix remodeling, interstitial fibrosis, fatty infiltration, and changes in the 3-dimensional cellular architecture of the working myocardium.7,8 Over the last 17 years, the study of the molecular genetic basis of monogenic cardiac rhythm disorders, together with characterization of functional expression and biophysical properties of mutant channels from patients with inheritable ion channel diseases, has significantly advanced our understanding of the molecular basis of cardiac arrhythmias.9 Yet, this clearly has not been sufficient. Despite such advances, predictable prevention of AF or VF is currently not possible and the development of effective antiarrhythmic pharmacological agents has been extremely difficult. Not all questions related to arrhythmia mechanisms are directly answerable by reductionist experiments such as DNA sequencing or patch clamping. There is a hierarchy of questions whose levels are determined by the generality of the answers sought. Thus the question of what a mutation in an ion …

Comparison of the diagnostic value between ECG and dynamic ECG for coronary heart disease arrhythmias

Objective To investigate and compare the clinical values of routine electrocardiogram and dynamic electrocardiogram in arrhythmia in coronary heart disease diagnosis.Methods 73 patients with coronary heart disease were collected and monitored by routine electrocardiogram and dynamic electrocardiogram,and two groups were e stablished including control group using routine electrocardiogram and observation group using dynamic electrocardiogram.The positive diagnosis rate and the specific diagnosis diresults of arrhythmia in coronary heart disease of both groups were compared.Results The positive diagnosis rate of arrhythmia in coronary heart disease of observation group(75.3％ ) was significantly higher than that of control group(54.8％ ) ( x2 =6.78,P ＜0.05).And the positive diagnosis rate of the observation group was also significantly higher than that of the control group in ventricular premature beats two,triple law,pairs of premature ventricular contractions,atrial premature beats two,triple law,atrial premature beats in pairs,atrioventricular block and paroxysmal ventricular tachycardia( all P ＜ 0.05 ).Conclusion Compared with routine electrocardiogram,the dynamic electrocardiogram in anrnythmia in coronary heart disease diagnosis could obtain higher positive diagnosis rate,and it is worthy of clinical application. Key words: Routine electrocardiogram; Dynamic electrocardiogram; Coronary heart disease; Arrhythmia

Modulated dispersion of activation and repolarization by premature beats in patients with cardiomyopathy at risk of sudden death

Premature beats can trigger ventricular arrhythmias in heart disease, but the mechanisms are not well defined. We studied the effect of premature beats on activation and repolarization dispersion in seven patients with cardiomyopathy (57 ± 10 yr, left ventricular ejection fraction 31 ± 7%). Activation time (AT), activation-recovery interval (ARI), and total repolarization time (TRT) were measured from 26 unipolar electrograms during right ventricle (RV) endocardial (early) to left ventricle epicardial (late) activation in response to RV apical extrastimulation (S1S2). Early TRT dispersion increased significantly with shorter S1S2 (1.0 ± 0.2 to 2.3 ± 0.4 ms/mm, P < 0.0001), with minimal change in late TRT dispersion (0.8 ± 0.1 to 1.0 ± 0.3 ms, P = 0.02). This was associated with an increase in early AT dispersion (1.0 ± 0.1 to 1.5 ± 0.2 ms/mm, P = 0.05) but no change in late AT dispersion (0.6 ± 0.1 to 0.7 ± 0.2 ms/mm, P = 0.4). Early and late ARI dispersion did not change with shorter S1S2. AT restitution slopes were similar between early and late sites, as was slope heterogeneity. ARI restitution slope was greater in early vs. late sites (1.3 ± 0.6 vs. 0.8 ± 0.6, P = 0.03), but slope heterogeneity was similar. With shorter S1S2, AT-ARI slopes became less negative (flattened) at both early (-0.4 ± 0.1 to +0.04 ± 0.2) and late (-1.5 ± 0.2 to +0.3 ± 0.2) sites, implying less activation-repolarization coupling. There was no difference in AT-ARI slopes between early and late sites at short S1S2. In conclusion, high-risk patients with cardiomyopathy have greater TRT dispersion at tightly coupled S1S2 due to greater AT dispersion and activation-repolarization uncoupling. Modulated dispersion is more pronounced at early vs. late activated sites, which may predispose to reentrant ventricular arrhythmias.

Improving safety in the electrophysiology laboratory using a simple radiation dose reduction strategy: a study of 1007 radiofrequency ablation procedures

BackgroundThe use of fluoroscopic screening involves exposure to ionising radiation for both patients and operators.ObjectiveTo assess the effects of radiation dose reduction manoeuvres (DRM) during radiofrequency ablation (RFA) procedures.DesignProspective study...

Characteristics and admission patterns of patients presenting with syncope to U.S. emergency departments, 1992-2000.

To describe the characteristics and admission patterns of patients with syncope presenting to U.S. emergency departments (EDs). The ED portion of the National Hospital Ambulatory Medical Care Survey, 1992-2000, was analyzed. Nationally representative weighted estimates for incidence and admission rates were estimated and stratified by demographic variables. Presence of cardiovascular diagnoses on ED discharge was noted. Of the 865 million ED visits during the nine-year study period, an estimated 6.7 million (0.77%; 95% confidence interval [95% CI] = 0.69% to 0.85%) were related to syncope. Higher incidences of ED visits for syncope were found in elder, female, and non-Hispanic patients compared with their reference groups. The overall admission rate was 32% (95% CI = 28% to 36%). Older, male, and white patients were admitted more frequently than their counterparts. Of patients older than 80 years of age, 58% (95% CI = 49% to 67%) were admitted. Associated cardiovascular International Classification of Diseases, Ninth Revision (ICD-9), codes for ischemic, structural, and arrhythmic heart disease were noted in 10% (95% CI = 8% to 13%) of patients, and 66% (95% CI = 56% to 76%) of these patients were admitted. Syncope is a frequent reason for ED visits and admissions. Elders and patients with associated cardiovascular diagnoses are frequently discharged, and admission practices appear to deviate from consensus panel guidelines.

Characteristics and admission patterns of patients presenting with syncope to us emergency departments, 1992-2000

Study objectives: We describe the characteristics and admission patterns of patients with syncope presenting to US emergency departments (EDs). Methods: The ED portion of the National Hospital Ambulatory Medical Care Survey, 1992-2000, was analyzed. Nationally representative weighted estimates for incidence and admission rates were estimated and stratified by demographic variables. Presence of cardiovascular diagnoses on ED discharge was noted. Results: Of the 865 million ED visits during the 9-year study period, an estimated 6.7 million (0.77%; 95% confidence interval [CI] 0.69% to 0.85%) were related to syncope. Higher incidences of ED visits for syncope were found in elderly, female, and non-Hispanic patients compared with their reference groups. The overall admission rate was 32% (95% CI 28% to 36%). Older, white, and male patients were admitted more frequently than their counterparts. Of patients older than 80 years, 58% (95% CI 49% to 67%) were admitted. Associated cardiovascular International Classification of Diseases, Ninth Revision codes for ischemic, structural, and arrhythmic heart disease were noted in 10% (95% CI 8% to 13%) of patients, and 66% (95% CI 56% to 76%) of these patients were admitted. Conclusion: Syncope is a frequent reason for ED visits and admissions. The elderly and patients with associated cardiovascular diagnoses are frequently discharged, and admission practices appear to deviate from consensus panel guidelines.

Human cardiac inwardly rectifying current IKir2.2 is upregulated by activation of protein kinase A.

The cardiac inwardly rectifying potassium current IK1 and its molecular correlates Kir2.1 and Kir2.2 play an important role in cardiac repolarisation and in the pathogenesis of hereditary long-QT syndrome (LQTS-7). Protein kinases A (PKA) and C (PKC) are key enzymes in adrenergic signal transduction, inducing arrhythmias in heart disease. This study investigated the regulation of Kir2.2 (KCNJ12) by PKA. Cloned Kir2.2 channels were expressed heterologously in Xenopus oocytes and currents were measured with the double-electrode voltage-clamp technique. After activation of PKA by forskolin (100 micromol/l) or Ro-20-1724 (100 micromol/l), wild type currents at -120 mV were increased by 93.7% and 79.0%, respectively. Coapplication of the PKA inhibitor KT-5720 (2.5 micromol/l) attenuated this effect. No significant changes were apparent after mutation of the single PKA consensus site S430. In addition, removal of all four PKC consensus sites in Kir2.2 induced a phorbolester-mediated current increase which could be suppressed by PKA inhibitors H-89 (50 micromol/l) and KT-5720 (2.5 micromol/l). This study demonstrates antagonistic effects of PKA and PKC in the regulation of Kir2.2. Phosphorylation by PKC has been shown to cause an inhibition of Kir2.2 currents, whereas activation of PKA leads to current upregulation.

Microfibrosis produces electrical load variations due to loss of side-to-side cell connections: a major mechanism of structural heart disease arrhythmias.

The purpose of this article is to demonstrate how adaptive changes in myocardial microstructure provide mechanisms for emergent new conduction disturbances that initiate reentrant arrhythmias. The mechanisms are based on discontinuous conduction phenomena produced by increases in cellular loading; these increases result from changes in the normal distribution of the gap junctions. Recent studies that at a microscopic level propagation in normal mature cardiac muscle is stochastic. For example, the nonuniform and irregular distribution of the gap junctions in such normal muscle produces load variations that are associated with changes in Vmax inside individual cells during both longitudinal and transverse propagation. The stochastic nature of normal propagation at a microscopic level offers considerable protection against arrhythmias by reestablishing the general trend of wavefront movement after small variations in excitation events occur. If such microscopic diversity is decreased, large fluctuations in load develop that are distributed over more cells than usual. The decrease in diversity may be caused by loss of side-to-side coupling between fibers, which produces relatively isolated groups of cells with microfibrosis. With loss of side-to-side fiber coupling, the myocardial architecture may fail to reestablish a smoothed wavefront at the macroscopic level. Spatial nonuniformities of electrical loading then give rise to conduction block and reentry.

The Value of Oral Amiodarone in the Treatment of Ventricular Arrhythmias in Heart Disease

The antiarrhythmic properties of amiodarone at the ventricular level were discovered in the early 1970s. The unanimously recognised efficacy of amiodarone includes a weak negative inotropic effect and compensatory vasodilatory properties, making amiodarone particularly suitable for treating the potentially malignant arrhythmias associated with organic disease. In a review of 611 hospitalised patients on amiodarone, and 353 patients in whom the drug had been prescribed, over a 52-month period in our 60-bed department, we noted that amiodarone was prescribed in 53% of patients for arrhythmias and in 47% of patients for coronary insufficiency. Ventricular arrhythmias represented 13% of the rhythmic indications. These indications differ from those in the USA. The efficacy (70 to 90%) of amiodarone in ventricular extrasystoles has been shown in open studies. In coronary patients, the antiarrhythmic activity of amiodarone is superior to that of propranolol. However, there has been no controlled study because the need for a loading dosage, and the electrocardiographic effects render such studies difficult. After myocardial infarction, ventricular arrhythmias constitute a significant risk factor independently of prognosis; amiodarone may be useful in this indication, and studies of the European Myocardial Infarction Amiodarone Trial (EMIAT) type will examine its value here. Since 1973, it has been recognised that amiodarone can prevent ventricular tachycardia in 55 to 89% of patients in the clinical situation. After a long-standing controversy, the positive predictive value of programmed stimulation has finally been agreed on. In hypertrophic cardiomyopathy, retrospective studies suggest a reduction in mortality in patients treated with amiodarone. By contrast, the value of amiodarone in dilated cardiomyopathy requires more intensive investigation. We consider amiodarone to be indicated in ventricular arrhythmic complexes, particularly if they are associated with an ejection fraction of less than 35% and/or atrial fibrillation. The value of amiodarone in arrhythmias associated with heart failure needs to be evaluated. In conclusion, amiodarone is a powerful antiarrhythmic agent but, because of the possibility of dose- and duration-dependent side effects, evaluation of the risk: benefit ratio in each indication is needed.

Evaluation of transthoracic countershock with initial energy levels up to 200 J in a coronary care unit

In a five year prospective study, transthoracic countershock of patients in the coronary care unit was evaluated with respect to efficacy, transthoracic resistance and arrhythmias. Those patients dying within 12 hours of the recorded event are referred to as agonal patients. Atrial arrhythmias were generally first treated with quinidine or disopyramide and/or a digitalis preparation. Patients with coronary heart disease were treated with lidocaine, disopyramide, or verapamil when there was time for appropriate diagnosis. The efficacy of the first shock with an energy level between 50 J and 200 J in non-agonal patients was: for atrial fibrillation, 44% (N = 34), and between 83% and 93% for tachycardias and ventricular fibrillation. The cumulative efficacy of two shocks with energy levels between 50 J and 200 J was: in atrial fibrillation 53% and others between 90% and 96%. In agonal patients with ventricular fibrillation and acute myocardial infarction the efficacy of one shock of 100-150 J was 39% and two shocks of 100-200 J, 69% (N = 13). No correlation was found between the transthoracic resistance and parameters such as body-weight, length or thorax-circumference, indicating that these should not be taken into account in the choice of the energy level for countershock. In non-agonal patients without coronary heart disease arrhythmias due to countershock increased in duration when the energy of the countershock increased (p less than 0.01, N = 39). It is concluded that the initial stored energy for defibrillation and cardioversion of nonagonal patients in a coronary care unit may be limited to 200 J (160 J delivered energy), even with atrial fibrillation after drug therapy in which case an initial energy level of 200 J seems more appropriate.