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Annual International Conference of the... Jul 2019Dofetilide is an antiarrhythmic drug that selectively inhibits the rapid component of the delayed rectifier potassium current. The administration of dofetilide may cause...
Dofetilide is an antiarrhythmic drug that selectively inhibits the rapid component of the delayed rectifier potassium current. The administration of dofetilide may cause ventricular arrhythmias and torsade de pointes. Electrocardiographic (ECG) microvolt T-wave alternans (TWA), an electrophysiologic phenomenon consisting in the beat-to-beat alternation of the T-wave amplitude requiring computerized algorithms to be detected, has also been associated to malignant ventricular arrhythmias. Aim of the present study was to evaluate if dofetilide induces TWA during the 24 hours following administration. The study population consisted of 22 healthy subjects ("ECG Effects of Ranolazine, Dofetilide, Verapamil, and Quinidine in Healthy Subjects" database by Physionet) to whom a 500 μg-dose of dofetilide was administered. For each subject, 10 s ECG were acquired at baseline (0.5 hour before dofetilide administration) and at 15 time points during the 24 hours following the drug administration. ECG were then processed for automatic TWA detection by correlation method. In 21 subjects out of 22, after dofetilide administration, TWA significantly increased to a peak value (median TWA values went from 6 μV at baseline to a max 32 μV; p<; 0.05), on average after 5 hours, to then come back to values closer to baseline. Thus, in healthy subjects, dofetilide increases occurrence and levels (6 times baseline value on average) of TWA in the hours following its administration.
Topics: Arrhythmias, Cardiac; Electrocardiography; Humans; Phenethylamines; Sulfonamides
PubMed: 31945853
DOI: 10.1109/EMBC.2019.8857486 -
International Journal of Cardiology May 2006Microvolt T-wave alternans (TWA) testing involves measuring variation in the morphology of the T-wave on an every other beat basis. The magnitude of the variation... (Review)
Review
Microvolt T-wave alternans (TWA) testing involves measuring variation in the morphology of the T-wave on an every other beat basis. The magnitude of the variation observed is typically on the order of a few microvolts. Thus in order to detect microvolt TWA, specialized recording and signal processing methods must be employed for reliable measurement. Additionally, microvolt TWA is not generally present at rest even in patients at risk of ventricular tachyarrhythmias and therefore exercise stress, pharmacologic stress, or atrial pacing must be utilized in order to elevate the heart rate. A positive MTWA test is one in which sustained TWA is present with an onset heart rate < or = 110 bpm. With current instrumentation, microvolt TWA represents an inexpensive, convenient non-invasive testing modality. Microvolt TWA has been evaluated prospectively in a variety of patient populations as a means of predicting occurrence of ventricular tachyarrhythmic events and its association with the genesis of ventricular arrhythmias has been demonstrated. Future role of microvolt TWA testing in noninvasive risk stratification is awaiting results of ongoing clinical trials. In this article, we tried to review the techniques, interpretation, indications, clinical studies, and future perspectives of microvolt TWA.
Topics: Anti-Arrhythmia Agents; Biomarkers; Cardiomyopathy, Dilated; Cardiomyopathy, Hypertrophic; Electrocardiography; Heart Rate; Humans; Sympathetic Nervous System; Ventricular Fibrillation
PubMed: 16054250
DOI: 10.1016/j.ijcard.2005.06.049 -
International Journal of Cardiology Sep 2013The ability of microvolt T-wave alternans (MTWA) for risk stratification of cardiac events in patients with ischemic cardiomyopathy (ICM) has not been well established. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The ability of microvolt T-wave alternans (MTWA) for risk stratification of cardiac events in patients with ischemic cardiomyopathy (ICM) has not been well established.
METHODS
The authors systematically reviewed current literature and carried out a meta-analysis to determine the ability of MTWA to predict the outcome severity after ICM. Major endpoints include composite endpoint of cardiac mortality and severe arrhythmic events in primary prevention of patients with ICM, as well as all-cause mortality (cardiac death, and/or non-cardiac death).
RESULTS
Seven trials were included by using MTWA for risk stratification of cardiac events in 3385 patients with ICM. All patients were distributed into two groups according to the results of MTWA tests: non-negative group included positive and indeterminate, and negative group. Compared with the negative group, non-negative group showed increased rates of cardiac mortality or severe arrhythmic events (RR=1.65, 95%CrI=1.32, 2.071), sudden cardiac death (SCD) (RR=2.04 95%CrI=1.11, 3.75), and all-cause mortality (RR=2.11, 95%CrI=1.60, 2.79). The funnel plot revealed that there might be bias within current publications. The fail-safe number of composite endpoint and all-cause mortality was 14.42 and 18.93, respectively (when P=0.01). The fail-safe number of SCD was 1.07 (when P=0.05), which may be caused by the small case number of included studies and some patients with ICD included.
CONCLUSIONS
The non-negative group of MTWA had a nearly double risk of severe outcomes compared with the negative group. Therefore, MTWA represents a potential useful tool for judging the severity of ICM.
Topics: Cardiomyopathies; Clinical Trials as Topic; Electrocardiography; Humans; Myocardial Ischemia; Risk Assessment
PubMed: 22683284
DOI: 10.1016/j.ijcard.2012.05.050 -
Expert Review of Cardiovascular Therapy Jul 2008Extensive research and clinical interest has focused recently on use of microvolt T-wave alternans (MTWA) as a means for sudden death risk stratification in patients... (Review)
Review
Extensive research and clinical interest has focused recently on use of microvolt T-wave alternans (MTWA) as a means for sudden death risk stratification in patients with cardiomyopathy. Emphasis has been placed on determining whether MTWA testing can more accurately identify high-risk patients from the broad population who are potentially eligible for prophylactic implantable cardioverter defibrillators. More recent studies seek to determine if additional patients not currently covered by primary prevention implantable cardioverter defibrillator guidelines could be defined using MTWA. Unfortunately, accumulation of clinical data has not necessarily led to clarity in the minds of the end-users as to the role of MTWA in clinical practice. This article serves to provide background information, selective review of relevant studies, and a perspective on where the field stands today. A general framework for incorporating MTWA into clinical practice is presented.
Topics: Arrhythmias, Cardiac; Clinical Trials as Topic; Death, Sudden, Cardiac; Defibrillators, Implantable; Electrocardiography; Humans; Practice Guidelines as Topic; Risk Assessment; Risk Factors
PubMed: 18570621
DOI: 10.1586/14779072.6.6.833 -
BMC Cardiovascular Disorders Jan 2009Studies have demonstrated that the use of implantable cardioverter defibrillators (ICDs) is effective for the primary prevention of arrhythmic events but due to imposing... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Studies have demonstrated that the use of implantable cardioverter defibrillators (ICDs) is effective for the primary prevention of arrhythmic events but due to imposing costs, there remains a need to identify which patients will derive the greatest benefit. Microvolt T-wave alternans (MTWA) has been proposed to assist in this stratification.
METHODS
We systematically searched the literature using MEDLINE, EMBASE, Current Contents, the Cochrane Library, INAHTA, and the Web of Science to identify all primary prevention randomized controlled trials and prospective cohort studies with at least 12 months of follow-up examining MTWA as a predictor of mortality and severe arrhythmic events in patients with severe left-ventricular dysfunction. The search was limited to full-text English publications between January 1990 and May 2007. The primary outcome was a composite of mortality and severe arrhythmias. Data were synthesized using Bayesian hierarchical models.
RESULTS
We identified no trials and 8 published cohort studies involving a total of 1,946 patients, including 332 positive, 656 negative, 84 indeterminate, and 874 non-negative (which includes both positive and indeterminate tests) MTWA test results. The risk of mortality or severe arrhythmic events was higher in patients with a positive MTWA compared to a negative test (RR = 2.7, 95% credible interval (CrI) = 1.4, 6.1). Similar results were obtained when comparing non-negative MTWA to a negative test.
CONCLUSION
A positive MTWA test predicts mortality or severe arrhythmic events in a population of individuals with severe left ventricular dysfunction. However, the wide credible interval suggests the clinical utility of this test remains incompletely defined, ranging from very modest to substantial. Additional high quality studies are required to better refine the role of MTWA in the decision making process for ICD implantation.
Topics: Arrhythmias, Cardiac; Controlled Clinical Trials as Topic; Cost-Benefit Analysis; Defibrillators, Implantable; Exercise Test; Humans; MEDLINE; Predictive Value of Tests; Quality Assurance, Health Care; Sensitivity and Specificity; Ventricular Dysfunction, Left
PubMed: 19175926
DOI: 10.1186/1471-2261-9-5 -
International Journal of Cardiology 2015
Observational Study
Topics: Adult; Chagas Cardiomyopathy; Cross-Sectional Studies; Electrocardiography; Female; Humans; Male; Middle Aged
PubMed: 25828299
DOI: 10.1016/j.ijcard.2015.03.253 -
Journal of the American College of... Jul 2005The objective of this study was to perform a meta-analysis of the predictive value of microvolt T-wave alternans (MTWA) testing for arrhythmic events in a wide variety... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
The objective of this study was to perform a meta-analysis of the predictive value of microvolt T-wave alternans (MTWA) testing for arrhythmic events in a wide variety of populations.
BACKGROUND
Previous studies describing the use of MTWA as a predictor of ventricular tachyarrhythmic events have been limited by small sample sizes and disparate populations.
METHODS
Prospective studies of the predictive value of exercise-induced MTWA published between January 1990 and December 2004 were retrieved. Data from each article were abstracted independently by two authors using a standardized protocol. Summary estimates of the predictive value of MTWA were made using a random-effects model.
RESULTS
Data were accumulated from 19 studies (2,608 subjects) across a wide range of populations. Overall, the positive predictive value of MTWA for arrhythmic events was 19.3% at an average of 21 months' follow-up (95% confidence interval [CI] 17.7% to 21.0%), the negative predictive value was 97.2% (95% CI 96.5% to 97.9%), and the univariate relative risk of an arrhythmic event was 3.77 (95% CI 2.39 to 5.95). There was no difference in predictive value between ischemic and nonischemic heart failure subgroups. The positive predictive value varied depending on the population of patients studied (p < 0.0001).
CONCLUSIONS
Microvolt T-wave alternans testing has significant value for the prediction of ventricular tachyarrhythmic events; however, there are significant limitations to its use. The predictive value of MTWA varies significantly depending on the population studied. Careful standardization is needed for what constitutes abnormal MTWA. The incremental prognostic value of MTWA when used with other methods of risk stratification is unclear.
Topics: Adult; Electrocardiography; Female; Heart Conduction System; Humans; Male; Middle Aged; Predictive Value of Tests; Reproducibility of Results; Risk Assessment; Tachycardia, Ventricular
PubMed: 15992639
DOI: 10.1016/j.jacc.2005.03.059 -
Anatolian Journal of Cardiology Nov 2016
Topics: Arrhythmias, Cardiac; Electrocardiography; Humans; Risk Assessment
PubMed: 27872443
DOI: 10.14744/AnatolJCardiol.2016.21130 -
Journal of Cardiovascular... Sep 2010
Topics: Adrenergic beta-Antagonists; Defibrillators, Implantable; Drug Administration Schedule; Electric Countershock; Electrophysiologic Techniques, Cardiac; Humans; Patient Selection; Predictive Value of Tests; Primary Prevention; Risk Assessment; Risk Factors; Tachycardia, Ventricular; Treatment Outcome; Ventricular Dysfunction, Left
PubMed: 20455986
DOI: 10.1111/j.1540-8167.2010.01794.x -
Journal of the American Heart... Dec 2021Background Unlike T-wave alternans (TWA), the relation between QRS alternans (QRSA) and ventricular arrhythmia (VA) risk has not been evaluated in hypertrophic...
Background Unlike T-wave alternans (TWA), the relation between QRS alternans (QRSA) and ventricular arrhythmia (VA) risk has not been evaluated in hypertrophic cardiomyopathy (HCM). We assessed microvolt QRSA/TWA in relation to HCM risk factors and late VA outcomes in HCM. Methods and Results Prospectively enrolled patients with HCM (n=130) with prophylactic implantable cardioverter-defibrillators underwent digital 12-lead ECG recordings during ventricular pacing (100-120 beats/min). QRSA/TWA was quantified using the spectral method. Patients were categorized as QRSA+ and/or TWA+ if sustained alternans was present in ≥2 precordial leads. The VA end point was appropriate implantable cardioverter-defibrillator therapy over 5 years of follow-up. QRSA+ and TWA+ occurred together in 28% of patients and alone in 7% and 7% of patients, respectively. QRSA magnitude increased with pacing rate (1.9±0.6 versus 6.2±2.0 µV; =0.006). Left ventricular thickness was greater in QRSA+ than in QRSA- patients (22±7 versus 20±6 mm; =0.035). Over 5 years follow-up, 17% of patients had VA. The annual VA rate was greater in QRSA+ versus QRSA- patients (5.8% versus 2.0%; =0.006), with the QRSA+/TWA- subgroup having the greatest rate (13.3% versus 2.6%; <0.001). In those with <2 risk factors, QRSA- patients had a low annual VA rate compared QRSA+ patients (0.58% versus 7.1%; =0.001). Separate Cox models revealed QRSA+ (hazard ratio [HR], 2.9 [95% CI, 1.2-7.0]; =0.019) and QRSA+/TWA- (HR, 7.9 [95% CI, 2.9-21.7]; <0.001) as the most significant VA predictors. TWA and HCM risk factors did not predict VA. Conclusions In HCM, microvolt QRSA is a novel, rate-dependent phenomenon that can exist without TWA and is associated with greater left ventricular thickness. QRSA increases VA risk 3-fold in all patients, whereas the absence of QRSA confers low VA risk in patients with <2 risk factors. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02560844.
Topics: Arrhythmias, Cardiac; Cardiomyopathy, Hypertrophic; Humans; Risk Factors
PubMed: 34854315
DOI: 10.1161/JAHA.121.022036