Use Of T-wave Alternans Research Articles

Quantitative T-wave alternans analysis for sudden cardiac death risk assessment and guiding therapy: answered and unanswered questions: For: Proceedings of ICE2015 Comandatuba, Brazil, Sudden Death Symposium

This review addresses current questions regarding use of T-wave alternans to stratify risk for sudden cardiac death. Both of the currently available commercial methodologies, namely, the frequency-domain spectral method and the time-domain modified moving average (MMA) method, are supported by guideline statements, cleared by the US FDA, and covered by the US Center for Medicare and Medicaid services. Similar numbers of patients have been enrolled in predictive studies; odds ratios generated by the two methods are similar including in a head-to-head study. However, in two prospective studies, prediction by TWA with the spectral method was negative, likely due to withdrawal of beta-blockade before the test with later resumption, while all studies with MMA have achieved prediction when the commercial software was used appropriately. Questions currently undergoing investigation include TWA's potential to guide ICD implantation, to track changes in risk during cardiac disease progression, and to evaluate the adequacy of medical therapy.

Clinical applications of T-wave alternans assessed during exercise stress testing and ambulatory ECG monitoring

Analytical methods to measure T-wave alternans (TWA), a beat-to-beat fluctuation in the morphology of the ST-segment and T wave in the electrocardiogram (ECG), have been developed to address the unmet challenge of identifying individuals at increased risk for sudden cardiac death. Conventional noninvasive markers including left ventricular ejection fraction have significant limitations as many individuals who die suddenly have relatively preserved ventricular mechanical function. TWA is an attractive marker as it is closely linked to ECG heterogeneity and abnormalities in calcium handling, key factors in arrhythmogenesis. The objectives of this review are to summarize the clinical evidence supporting use of TWA in risk stratification and to discuss its current and potential applications in guiding device and medical therapy.

第12回体表心臓微小電位研究会 シンポジウム 抗不整脈薬の体表心臓微小電位記録による評価―加算平均心電図, T wave alternansなどのよる検討― 抗不整脈薬の効果判定の指標としてのT-wavealternansの有用性

第12回体表心臓微小電位研究会 シンポジウム 抗不整脈薬の体表心臓微小電位記録による評価―加算平均心電図, T wave alternansなどのよる検討― 抗不整脈薬の効果判定の指標としてのT-wavealternansの有用性

An Overview of Current Strategies of Risk Assessment for Sudden Cardiac Death

Sudden cardiac death (SCD) remains one of the major challenges of contemporary cardiology. Major clinical trials have demonstrated that primary prophylaxis of implantable cardioverter-defibrillators (ICD) is effective in saving lives when applied to patients with a reduced cardiac function. However, absolute mortality reduction with ICD therapy was not so high. Thus, primary ICD prophylaxis would subject a large group of patients to extend life in only a small population (i.e., costly strategy). Although left ventricular ejection fraction (LVEF) is a gold standard in risk stratification for SCD, some of electrocardiographic (ECG) techniques or measurements are also utilized in identifying high-risk groups. Various ECG indices that reflect repolarization, depolarization, or autonomic abnormalities have been used as risk stratification markers. Clinical evidence supports the usefulness of T-wave alternans (TWA), heart rate turbulence (HRT), heart rate variability (HRV), late potentials (LP) by signal-averaged electrocardiography, and so on. However, positive predictive values of these markers are low in identifying patients at risk for SCD. At present, combined assessment of two or three noninvasive markers has been performed in clinical practice to increase predictive accuracy. In this session, we will overview current risk stratification techniques or measurements including standard, alternative, and new ECG markers for preventing SCD.

Role of the surface electrocardiogram in developing countries

The surface electrocardiogram (ECG) is a basic cardiac investigation delivering information not only regarding heart rhythm but also regarding ischemic disease, effects of hypertension, congenital syndromes, and cardiomyopathies. These may determine decisions regarding follow-up investigations or treatment. The ECG fulfils several characteristics of a good screening test: it is rapid, is noninvasive, requires minimal technical expertise to perform, and is inexpensive. However, its interpretation requires highly trained physicians. In industrialized nations, the test is performed routinely in outpatient clinics and hospitals frequently in conjunction with further cardiac imaging. Developing nations confront a different situation. Urbanized segments may access ECG testing similarly to industrialized countries. However, in a country such as India, 80% of population is rural and poor. Less than 30% of physicians are rurally located, and most are primary care physicians. Access to medical care is limited by sparse and underresourced medical facilities and personnel, poorer socioeconomic status, ignorance of disease, and lack of motivation to seek health care. The ECG may be the only affordable cardiac test for this population, but poor communications (transport, telephone) hamper access. Initiatives to overcome these obstacles are being undertaken in some model situations. For example in Bangalore, India, use of mobile vans equipped with satellite terminals (aided by the Indian Space Research Organization) permits transmission of ECGs from rural points to central urban hospitals for physician interpretation. The physician community has responsibilities of improving the diagnostic yield from the ECG. Rural communities have a different spectrum of diseases with lesser coronary artery disease and greater incidence of valvular disease. The ECG has different roles in these diseases. (In contrast, urban communities in the same country experience diseases of industrialized nations.) Electrocardiogram interpretation also needs to account for different “normal” values in different ethnic groups: there is a surprising dearth of such data in groups other than African Americans. This is essential for interpretation of abnormality. Development of additional sophisticated analyses from ECG data may guide more selective use of expensive and invasive therapies. For example, risk stratification for defibrillator implant may be enhanced by use of T-wave alternans and heart rate variability. In China, ischemia monitoring with 12-lead Holters is performed due to lack of availability of a chest pain clinic. Innovative measures in electrocardiography are required for improving health care delivery in developing nations.

Usefulness of T-wave alternans in sudden death risk stratification and guiding medical therapy.

Visible T-wave alternans (TWA), a beat-to-beat alternation in the morphology and amplitude of the ST segment or T wave, has been observed for over a century to occur in association with life-threatening arrhythmias in patients with acute coronary syndrome, heart failure, and cardiac channelopathies. This compelling linkage prompted development of quantitative techniques leading to FDA-cleared commercial methodologies for measuring nonvisible levels of TWA in the frequency and time domains. The first aim of this review is to summarize evidence from more than a hundred studies enrolling a total of >12,000 patients that support the predictivity of TWA for cardiovascular mortality and sudden cardiac death. The second focus is on the usefulness of TWA in guiding therapy. Until recently, TWA has been used primarily in decision making for cardioverter-defibrillator implantation. Its potential utility in guiding pharmacologic therapy has been underappreciated. We review clinical literature supporting the usefulness of TWA as an index of antiarrhythmic effects and proarrhythmia for different drug classes. Beta-adrenergic and sodium channel-blocking agents are the most widely studied drugs in clinical TWA investigations, with both reducing TWA magnitude; the exception is patients in whom sodium channel blockade discloses the Brugada syndrome and provokes macroscopic TWA. An intriguing possibility is that TWA may help to detect beneficial effects of nonantiarrhythmic agents such as the angiotensin II receptor blocker valsartan, which indirectly protects from arrhythmia through improving myocardial remodeling. We conclude that quantitative analysis of TWA has considerable potential to guide pharmacologic intervention and thereby serve as a therapeutic target.

AB14-5: Sudden death risk stratification in athletes with ventricular arrhythmias: Usefulness of T-wave alternans

AB14-5: Sudden death risk stratification in athletes with ventricular arrhythmias: Usefulness of T-wave alternans

Pathophysiological basis and clinical application of T-wave alternans.

We review the contemporary understanding of the pathophysiology of repolarization alternans and present a perspective on the use of T-wave alternans (TWA) as a risk stratification marker of malignant ventricular arrhythmias. Several studies have demonstrated a high correlation of susceptibility to ventricular arrhythmias and sudden cardiac death with the existence of TWA. We describe a number of cellular and molecular alterations in the diseased heart that may provide a link between electrical and mechanical alternans and arrhythmia susceptibility. Repolarization alternans is likely the result of distinct and diverse cellular and molecular alterations that are associated with exaggerated regional repolarization heterogeneity, which renders the heart susceptible to malignant arrhythmias.