Ambulatory ECG-based T-wave alternans predicts sudden cardiac death in high-risk post-MI patients with left ventricular dysfunction in the EPHESUS study

Background: Exercise microvolt T‐wave alternans (TWA) identifies sudden cardiac death (SCD) risk. TWA can be measured from ambulatory ECGs (AECGs) using modified moving average (MMA) method. Whether MMA TWA from AECGs predicts SCD in post‐MI patients with left ventricular dysfunction (LVD) is unknown. Methods: EPHESUS enrolled hospitalized post‐MI patients with heart failure and/or diabetes with LVD. Before randomization to drug treatment, AECGs were obtained in 493 patients. Of them, 46 died of cardiovascular causes, including 18 of SCD. Patients alive at end of follow‐up (N = 92) were matched with 46 nonsurvivors based on age, gender, and diabetes. MMA TWA was analyzed using MARSPC system (GE Healthcare, Milwaukee, WI, USA). The three highest TWA values from artifact‐free periods were averaged for AECG channels corresponding to leads V₁ and V₃. SCD prediction was tested with a prespecified 47 μV cutpoint and at a cutpoint maximizing the separation between SCD patients versus survivors or non‐SCD. Results: TWA in either lead was higher for patients with SCD (P ≤ 0.05) versus survivors or non‐SCD. TWA ≥ 47 μV was associated with RR = 5.2 (95%CI = 1.8–13.6, P = 0.002) in V₁ and RR = 5.5 (95% CI = 2.2–13.8, P < 0.001) in V₃ for SCD. The optimal cutpoint for TWA in V₁ was ≥43 μV (RR = 5.9 [95%CI = 2.2–15.8, P < 0.001]). The optimal cutpoint in V₃ was ≥47 μV. TWA greater than the optimal cutpoint in either lead was associated with RR = 7.1 (95%CI = 2.7–18.3, P < 0.001) for SCD, with 11 out of 18 patients dying of SCD. Conclusions: AECG‐based TWA measured with MMA is a powerful predictor of SCD in high‐risk post‐MI patients with LV dysfunction.     

Predictive value of microvolt T-wave alternans in patients with left ventricular dysfunction.

OBJECTIVES: The purpose of this study was to prospectively evaluate the utility of microvolt T-wave alternans (TWA) in predicting arrhythmia-free survival and total mortality in patients with left ventricular (LV) dysfunction. BACKGROUND: Microvolt TWA has been proposed as a useful tool in identifying patients unlikely to benefit from prophylaxis with implantable cardioverter-defibrillator (ICD) prophylaxis. METHODS: We evaluated 286 patients with an LV ejection fraction 相似文献   

Microvolt T-wave alternans and the risk of death or sustained ventricular arrhythmias in patients with left ventricular dysfunction.

OBJECTIVES: This study hypothesized that microvolt T-wave alternans (MTWA) improves selection of patients for implantable cardioverter-defibrillator (ICD) prophylaxis, especially by identifying patients who are not likely to benefit. BACKGROUND: Many patients with left ventricular dysfunction are now eligible for prophylactic ICDs, but most eligible patients do not benefit; MTWA testing has been proposed to improve patient selection. METHODS: Our study was conducted at 11 clinical centers in the U.S. Patients were eligible if they had a left ventricular ejection fraction (LVEF) < or =0.40 and lacked a history of sustained ventricular arrhythmias; patients were excluded for atrial fibrillation, unstable coronary artery disease, or New York Heart Association functional class IV heart failure. Participants underwent an MTWA test and then were followed for about two years. The primary outcome was all-cause mortality or non-fatal sustained ventricular arrhythmias. RESULTS: Ischemic heart disease was present in 49%, mean LVEF was 0.25, and 66% had an abnormal MTWA test. During 20 +/- 6 months of follow-up, 51 end points (40 deaths and 11 non-fatal sustained ventricular arrhythmias) occurred. Comparing patients with normal and abnormal MTWA tests, the hazard ratio for the primary end point was 6.5 at two years (95% confidence interval 2.4 to 18.1, p < 0.001). Survival of patients with normal MTWA tests was 97.5% at two years. The strong association between MTWA and the primary end point was similar in all subgroups tested. CONCLUSIONS: Among patients with heart disease and LVEF < or =0.40, MTWA can identify not only a high-risk group, but also a low-risk group unlikely to benefit from ICD prophylaxis.     

T-wave alternans in patients with right ventricular tachycardia

Microvolt T-wave alternans has been proposed as a new risk marker for ventricular arrhythmias. However, the clinical significance of T-wave alternans in patients with ventricular tachycardia (VT) originating from the right ventricle has been unknown. The study population consisted of 20 patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) or idiopathic VT. T-wave alternans was measured during bicycle exercise testing using the CH 2000 system. Of the 7 patients with ARVC, 6 (86%) were positive for T-wave alternans. On the other hand, only 1 (8%) of 13 patients with idiopathic VT originating from the right-ventricular outflow tract was positive for T-wave alternans.     

"Indeterminate" microvolt T-wave alternans tests predict high risk of death or sustained ventricular arrhythmias in patients with left ventricular dysfunction.

OBJECTIVES: This study tested the hypothesis that an "indeterminate" microvolt T-wave alternans (MTWA) test, when due to ectopy, unsustained MTWA, or low exercise heart rate (HR), has prognostic significance similar to a positive MTWA test. BACKGROUND: MTWA testing, used to stratify risk of sudden or total mortality in patients with structural heart disease, has been limited by a substantial number of "indeterminate" tests. Indeterminate tests are due to patient factors--excessive ventricular ectopy during exercise, unsustained MTWA, or failure to achieve a HR of 105 beats/min for 1 min--or technical factors such as a noisy recording or an exercise protocol that causes an excessively rapid rise in HR. METHODS: Patients in sinus rhythm with left ventricular ejection fraction < or =0.40 underwent MTWA exercise tests, analyzed with the spectral method and classified by a computerized interpretation algorithm. The primary end point was all-cause mortality or documented non-fatal sustained ventricular arrhythmia (SVA). "Indeterminate" tests were reviewed jointly by 2 readers blinded to subsequent events to determine the primary reason for indeterminacy. RESULTS: Participants (N = 549) were 56 +/- 13 years and 71% male; 49% had ischemic cardiomyopathy. There were 40 deaths and 11 non-fatal SVA. Most (94%) indeterminate results were due to patient factors. The 2-year rate for death or SVA was 17.8% in patients with an "indeterminate" MTWA test compared with 12.3% in those with a positive test. CONCLUSIONS: In patients with left ventricular dysfunction, an "indeterminate" MTWA test due to patient factors predicted death or SVA at least as well as a positive test.     

Prediction of sudden cardiac death in patients after acute myocardial infarction using T-wave alternans: a prospective study

Background and PurposeWe assessed the value of T-wave alternans (TWA) in prediction of sudden cardiac death (SCD) in patients with acute myocardial infarction (AMI).MethodsConsecutive patients (N = 227) were enrolled and were monitored with 24-hour ambulatory electrocardiogram within 1 to 15 days after AMI. T-wave alternans was identified by a modified moving average (MMA) algorithm computer software. The primary end point was SCD or lethal ventricular arrhythmia. We analyzed the hazard ratios (HRs) using the previously determined 47 μV TWA cutpoint.ResultsDuring the 16 ± 7-month follow-up, 10 (4.4%) patients died suddenly. T-wave alternans (≥47 μV) predicted SCD (HR, 17.78 [95% confidence interval, 3.75-84.31]; P < .0001). Moreover, patients with 5 or more TWA episodes (≥47 μV) were at higher risk for SCD (HR, 20.75 [95% confidence interval, 5.77-74.57]; P < .0001).ConclusionsT-wave alternans (≥47 μV) monitored at 1 to 15 days after AMI-predicted heightened risk of SCD. Prediction is improved when the frequency of TWA episodes (≥47 μV) is analyzed.     

T-wave inversion and diastolic dysfunction in patients with electrocardiographic left ventricular hypertrophy

Objectives

The aim of this study was to investigate if T-wave inversion (TWI) in the settings of electrocardiogram (ECG)–left ventricular hypertrophy (LVH) is associated with advanced diastolic dysfunction (DD) in subjects with preserved ejection fraction (EF).

Background

Animal studies suggested that an abnormal transmural repolarization sequence from endocardium to epicardium may contribute to DD. However, little is known about abnormal repolarization sequence and DD in humans.

Methods

We studied 231 patients with ECG-diagnosed LVH and with an EF of 50% or greater (measured within 6 months of the index ECG). T-wave inversion was assessed on leads I, aVL, V₄, V₅, or V₆. Diastolic dysfunction was defined based on echocardiographic estimation of the left atrial pressure. We used multiple logistic regression to estimate the odds ratio of DD comparing patients with TWI with those without TWI.

Results

The average age was 65.0 ± 14.2 years, and 61% were women. The mean EF was 61.8% ± 6.6%. Patients with TWIs were more likely to have coronary artery disease (P = .013) and diabetes (P = .007). There was a 5.6-fold increased odds of DD in patients with TWI compared with those without TWI in a model adjusting for sex, age, relative wall thickness, body mass index, hypertension, coronary artery disease, diabetes, hyperlipidemia, and smoking. When comparing different echocardiographic estimates of the left atrial pressure, patients with TWI displayed higher values for septal and lateral E/e′, left atrial volume index, and right ventricular/right atrial peak systolic gradient (P < .01 for each parameter).

Conclusions

T-wave inversion is associated with increased odds of DD in patients with ECG-LVH with preserved systolic function. The reversal of the normal sequence of repolarization manifested on the 12-lead ECG as TWI may be a factor to DD.     

Usefulness of microvolt T-wave alternans for prediction of ventricular tachyarrhythmic events in patients with dilated cardiomyopathy: results from a prospective observational study

OBJECTIVES: This study was designed to evaluate the ability of microvolt-level T-wave alternans (MTWA) to identify prospectively patients with idiopathic dilated cardiomyopathy (DCM) at risk of ventricular tachyarrhythmic events and to compare its predictive accuracy with that of conventional risk stratifiers. BACKGROUND: Patients with DCM are at increased risk of sudden death from ventricular tachyarrhythmias. At present, there are no established methods of assessing this risk. METHODS: A total of 137 patients with DCM underwent risk stratification through assessment of MTWA, left ventricular ejection fraction, baroreflex sensitivity (BRS), heart rate variability, presence of nonsustained ventricular tachycardia (VT), signal-averaged electrocardiogram, and presence of intraventricular conduction defect. The study end point was either sudden death, resuscitated ventricular fibrillation, or documented hemodynamically unstable VT. RESULTS: During an average follow-up of 14 +/- 6 months, MTWA and BRS were significant univariate predictors of ventricular tachyarrhythmic events (p < 0.035 and p < 0.015, respectively). Multivariate Cox regression analysis revealed that only MTWA was a significant predictor. CONCLUSIONS: Microvolt-level T-wave alternans is a powerful independent predictor of ventricular tachyarrhythmic events in patients with DCM.     

QT variability strongly predicts sudden cardiac death in asymptomatic subjects with mild or moderate left ventricular systolic dysfunction: a prospective study.

AIMS: The most widely accepted marker for stratifying the risk of sudden cardiac death (SCD) in post myocardial infarction patients is a depressed left ventricular function. Left ventricular ejection fractions (EF) of 35% or less increase the risk of sudden death but values between 35 and 40% raise concern. The underlying pathophysiological mechanism is sustained ventricular tachycardia or fibrillation, both associated with increased cardiac repolarization variability. We assessed whether the indices of QT variability from a short-term electrocardiographic (ECG) recording predict sudden death. METHODS AND RESULTS: A total of 396 subjects with chronic heart failure (CHF) due to post-ischaemic cardiomyopathy, with an EF between 35 and 40% and in NYHA class I, underwent a 5 min ECG recording to calculate the following variables: QT variance (QT(v)), QT normalized for the square of the mean QT (QTVN), and QT variability index (QTVI). Corrected QT (QT(c)) was calculated from a 12-lead ECG recording. All participants were followed for 5 years. A multivariable survival model indicated that a QTVI greater than or equal to the 80th percentile indicated a high risk of SCD [hazards ratio (HR) 4.6, 95% confidence interval (CI) 1.5-13.4, P = 0.006] and, though to a lesser extent, a high risk of total mortality (HR 2.4, 95% CI 1.2-4.9, P = 0.017). The model including QTVI as a continuous variable confirmed a similar high risk for SCD (HR 2.9, 95% CI 1.3-6.5, P = 0.01) and for total mortality (HR 2.6, 95% CI 1.3-5.2, P = 0.008). CONCLUSION: Although asymptomatic patients with CHF who have a slightly depressed EF are at low risk of sudden death, the category is extraordinarily numerous. The QTVI could be helpful in stratifying the risk of sudden death in this otherwise undertreated population.     

Post-systolic shortening during dobutamine stress echocardiography predicts cardiac survival in patients with severe left ventricular dysfunction

BACKGROUND: Patients with severe left ventricular dysfunction and myocardial viability by dobutamine stress echocardiography (DSE) or F18-fluorodeoxyglucose-single-photon emission computed tomography (FDG-SPECT), experience improved survival after coronary revascularization. Pulsed wave-tissue Doppler imaging (PW-TDI)-derived ejection phase shortening (EPS) and post-systolic shortening (PSS) velocities may help to quantify DSE. We assessed these variables in a prospective long-term follow-up. METHODS: Eighty patients (58 men, mean age 63+/-9 years) with left ventricular dysfunction (radionuclide ventriculography mean ejection fraction, 34+/-11%) underwent both DSE and FDG-SPECT for myocardial viability. Viable myocardium was improvement from rest to low dose or worsening of wall motion at peak DSE and normal perfusion, mildly reduced perfusion with FDG uptake or severely reduced or absent perfusion with increased FDG uptake (mismatch) at FDG-SPECT. EPS, PSS velocities and EPS/PSS ratio during DSE were analysed using a six-segment model. Coronary revascularization bypass grafting was performed in 62 patients. All patients completed a long-term (9-year) follow-up for cardiac death. RESULTS: The segmental prevalence of severe dyssynergy was 77%. On a patient basis myocardial viability was detected by EPS/PSS ratio (31%), FDG-SPECT (34%) and DSE (26%). A significant improvement of Kaplan-Meier survival was predicted in viable compared with nonviable revascularized patients (P < 0.01). Both EPS/PSS ratio and FDG-SPECT, compared to DSE alone, tended to allocate more accurately univariate prediction of death-free outcome (odds ratio, 2.5 and 2.7 compared with 2.1). CONCLUSIONS: TDI adds objective variables to DSE, helping to recognize viable myocardium and optimize prediction of death-free outcome in long-term follow-up, with favorable comparison with nuclear techniques.     

Tissue Doppler imaging predicts left ventricular dysfunction and mortality in a murine model of cardiac injury.

AIMS: Currently available non-invasive imaging methods frequently fail to detect alterations in left ventricular (LV) function despite histological evidence of injury. Tissue Doppler imaging (TDI) can detect subtle LV dysfunction. The aim of this study was to investigate whether TDI indices can predict LV systolic dysfunction and mortality following exposure to doxorubicin (DOX) in mice. METHODS AND RESULTS: TDI-derived peak endocardial systolic velocity (V(ENDO)) and strain rate (SR), as well as M-mode and two-dimensional indices of LV systolic function, were measured serially in mice after receiving DOX as a single dose (20 mg/kg). Haemodynamic measurements were obtained invasively before and at 1, 2, 4, and 5 days after the single DOX dose. Cardiac apoptosis was measured before and at 1 day after DOX. V(ENDO) and SR decreased after 1 and 2 days, respectively, whereas changes in fractional shortening (FS) and LV ejection fraction (LVEF) were not detected before 5 days. The reduction in both V(ENDO) and SR correlated with the decrease in dP/dt(MAX), and the change in V(ENDO) correlated with the early increase in cardiac cell apoptosis. In a subsequent experiment, DOX was administered at 4 mg/kg/week for 5 weeks, and LV function was followed serially for 16 weeks. In this chronic experiment, TDI indices decreased before FS and LVEF, correlated with late LV dysfunction, and predicted DOX-induced mortality. CONCLUSION: In a murine model of DOX-induced cardiac injury, TDI detects LV dysfunction prior to alterations in conventional echocardiographic indices and predicts mortality. This study suggests that TDI may be a reliable tool to detect early subtle changes in DOX-induced cardiac dysfunction.     

Effect of cardiac resynchronization therapy in patients with moderate left ventricular systolic dysfunction and wide QRS complex: a prospective study

Background: We sought to investigate the effect of cardiac resynchronization therapy (CRT) on disease progression in patients with moderate left ventricular (LV) systolic dysfunction.
Methods and Results: This is a prospective study to explore the effect of CRT in 15 optimally treated patients (age: 66.1 ± 12.8 years; male = 13) with New York Heart Association (NYHA) class III, LV ejection fraction >35% and <45% and QRS duration >120 msec. Echocardiographic examination and standard heart failure assessment was performed before and 3 months after CRT implantation. The magnitude of echocardiographic remodeling measurements was compared with 30 age, sex, NYHA class, and heart failure etiology matched patients with conventional CRT indication. There were significant reductions in LV end-systolic (86.2 ± 24.1 to 69.7 ± 22.2 mL, P < 0.01)/end-diastolic (135.5 ± 36.8 to 120.5 ± 34.6 mL, P < 0.01) volumes, improvement in LV ejection fraction (39.1 ± 2.2 to 44.2 ± 5.5%, P = 0.01), and NYHA class (3.0 ± 0.0 to 2.07 ± 0.46, P < 0.001). There was no difference in changes in LV volumes, ejection fraction, NYHA class, and exercise capacity before and after CRT between the study and conventional groups except for greater improvement in the quality of life score in the conventional group.
Conclusion: In this prospective study, significant LV reverse remodeling by CRT in those with a wide QRS complex and moderate LV systolic dysfunction was observed. Further studies to explore the benefit of CRT in patients with less severe heart failure are recommended.