Abnormal Microvolt T-wave Alternans Research Articles

Effects of Trimetazidine on T Wave Alternans in Stable Coronary Artery Disease.

Background and ObjectivesStudies reveal that the microvolt T wave alternans (MTWA) test has a high negative predictive value for arrhythmic mortality among patients with ischemic or non-ischemic cardiomyopathy. In this study, we investigate the effects of trimetazidine treatment on MTWA and several echocardiographic parameters in patients with stable coronary artery disease.Subjects and MethodsOne hundred patients (23 females, mean age 55.6±9.2 years) with stable ischemic heart disease were included in the study group. Twenty-five age- and sex-matched patients with stable coronary artery disease formed the control group. All patients were stable with medical treatment, and had no active complaints. Trimetazidine, 60 mg/day, was added to their current treatment for a minimum three months in the study group and the control group received no additional treatment. Pre- and post-treatment MTWA values were measured by 24 hour Holter testing. Left ventricular systolic and diastolic functions were assessed by echocardiography.ResultsAfter trimetazidine treatment, several echocardiographic parameters related with diastolic dysfunction significantly improved. MTWA has been found to be significantly improved after trimethazidine treatment (63±8 μV vs. 53±7 μV, p<0.001). Abnormal MTWA was present in 29 and 11 patients pre- and post-treatment, respectively (p< 0.001).ConclusionTrimetazidine improves MTWA, a non-invasive determinant of electrical instability. Moreover, several echocardiographic parameters related with left ventricular functions also improved. Thus, we can conclude that trimetazidine may be an effective agent to prevent arrhythmic complications and improve myocardial functions in patients with stable coronary artery disease.

Microvolt T-wave alternans in adult patients with repaired tetralogy of Fallot.

Indications for sudden cardiac death (SCD) primary prevention are unknown in patients with repaired tetralogy of Fallot (ToF). The role of microvolt T-wave alternans (MTWA) in SCD risk stratification was documented. However, the prevalence of spectral MTWA and its association with ventricular arrhythmia (VA) in adults after ToF repair were not elucidated. Microvolt T-wave alternans, electrocardiogram (ECG), ambulatory ECG monitoring, echocardiography, and spiroergometry were evaluated in 102 adults after ToF repair. Microvolt T-wave alternans results were classified as normal: negative(-), abnormal: positive(+), and indeterminate(ind). Owing to similar prognostic significance, MTWA(+) and MTWA(ind) due to patient factors were combined into nonnegative group: MTWA(abnormal). Microvolt T-wave alternans(abnormal) was more frequent in the studied group as compared with controls (P = .0005). The MTWA(abnormal) group had greater right ventricular end-diastolic diameter (P = .005), higher incidence of pulmonary regurgitation (P = .015), lower peak oxygen consumption (P = .01), and higher VE/VCO2 slope (P = .04) in comparison with MTWA(normal). Univariate logistic regression proved pulmonary regurgitation (OR = 3.57, 95% CI 1.27-10.04), VA (OR = 3.26, 95% CI 1.06-10.05), right ventricular end-diastolic enlargement (OR = 1.11, 95% CI 1.03-1.2), increase in VE/VCO2 slope (OR = 1.08, 95% CI 1.01-1.17), and decrease in peak oxygen uptake (OR = .91, 95% CI 0.83-0.99) to increase MTWA(abnormal) prevalence. In adults after ToF repair, abnormal MTWA occurred more often than in controls. Probability of abnormal MTWA did not rise with prevalence of malignant VA; however, presence of abnormal MTWA was associated with VA risk factors: pulmonary regurgitation, right ventricular enlargement, and consequent heart failure. The role of MTWA in selecting patients late after ToF repair at risk of SCD needs further observation.

Microvolt T-wave alternans in adults with complex congenital heart diseases

Sudden cardiac death (SCD) mostly resulting from ventricular arrhythmia remains a cause of mortality in 19-30% of adults with congenital heart defects. Indications for implantable cardioverter-defibrillators in primary prophylaxis are still under research. MicrovoltT wave alternans (MTWA) is one of the SCD risk stratification methods. We determined the incidence of MTWA in these patients and its coincidence with ventricular arrhythmia, as well as risk factors of ventricular arrhythmia/SCD. 204 patients with complex congenital heart anomalies and 45 healthy volunteers underwent ambulatory ECG monitoring, a cardiopulmonary test, B-type natriuretic peptide assessment, echocardiography and an MTWA test. After excluding technically inadequate traces, the remaining 179 patients and 43 controls were classified into MTWA positive (+), negative (-) and indeterminate (ind) subgroups. Additionally, MTWA (+) and MTWA (ind) formed an 'abnormal' group, labeled MTWA (non-). Abnormal MTWA was observed more frequently in the study group compared to controls (59 [33.0%] vs. 1 [2.3%], p = 0.000001). The MTWA (non-) group compared to MTWA (-) presented a higher number of males (61.0% vs. 37.5%, p = 0.005), predominance of patients with NYHA > I (44.1% vs. 25.0%, p = 0.007), pulmonary hypertension (16.9% vs. 0.8%, p = 0.00007), lower blood saturation (97% [73-100] vs. 99% [69-100], p = 0.0003), higher incidence of malignant arrhythmia (9 [15.2%] vs. 3 [2.5%], p = 0.003), lower peak oxygen consumption VO2 [mL/kg/min] (23.1 ± 5.9 vs. 26.3 ± 6.7, p = 0.002), higher VE//VCO2 slope (36.0 [25-74] vs. 31.0 [21-58], p = 0.01). Multivariate logistic regression analysis proved that pulmonary hypertension (OR = 13.7, p = 0.03), male gender (OR = 10.4,p = 0.00002), VE/VCO2 slope (OR = 1.07, p = 0.045) and VO2 (OR = 0.89, p = 0.04) increase the probability of MTWA (non-). Abnormal MTWA is more frequent in adults with congenital heart diseases than in the healthy population. Its probability increases in patients demonstrating clinical findings conducive to lethal arrhythmia like heart failure and pulmonary hypertension.

Is microvolt T‐wave alternans testing suitable for patients recently hospitalized due to decompensated heart failure?

We recently read with great interest the article by Jackson et al.1 concerning the prognostic value of microvolt T-wave alternans (MTWA) testing in patients who were recently hospitalized due to decompensated heart failure (HF). According to the authors, spectral MTWA testing was not widely applicable and failed to predict mortality in the studied group: the mortality rates of positive, negative, and indeterminate MTWA patients did not differ. On the basis of these findings, the authors concluded that MTWA testing cannot be endorsed as a risk stratification tool in HF patients. While reading this article, some questions occurred to us. Abnormal MTWA is most connected with sudden cardiac death (SCD).2 According to the literature, the total mortality rate in acute HF patients is high (24% at 1 year); however, only 6.7% are due to arrhythmias.3 Furthermore, Jackson et al.1 included patients with NYHA functional class IV. These patients have a higher rate of non-arrhythmic death and a lower rate of SCD than those with NYHA class I–III; therefore, they are normally excluded from studies with MTWA.4 Jackson et al.1 documented 46% of indeterminate MTWA among studied patients. This rate is higher than documented among chronic HF outpatients,5 which can influence the results. To decrease the number of indeterminate MTWA tests, many authors withdraw beta-blockers during the test.6 Of note, some patients after HF worsening need revascularization prior to MTWA testing, but this issue was not addressed in the cited article.1 Mean LVEF reported in the study was 40.2% (±12.2%).1 According to Merchant et al.,6 in patients with LVEF ≤35%, the all-cause mortality rates associated with a positive (9.7%) and indeterminate (12.2%) MTWA test are higher than in the case of negative testing (4.2%; P < 0.001). In contrast, when LVEF is >35%, the all-cause mortality rate associated with indeterminate testing (1.1%) is significantly lower than in the case of a positive MTWA test (6.2%). Therefore, the interpretation of indeterminate MTWA results should be based on LVEF range. We believe that the article1 undoubtedly contributes to better understanding of the prognosis of patients with decompensated HF. However, we are convinced that this group of patients is not appropriate for MTWA risk stratification analyses, and MTWA testing can be endorsed as a risk stratification tool in appropriately selected HF patients.

Microvolt T-wave alternans in adults with congenital heart diseases

Purpose: Sudden cardiac death (SCD) in adults with congenital heart diseases (CHD) is usually caused by ventricular arrhythmia (VA). Microvolt T-wave alternans (MTWA) proved its role in SCD risk stratification. Aim of study: Evaluation of spectral MTWA incidence in patients (P) with CHD and determination its association with VA and potential risk factors of SCD. Methods: Study group: 204P (93men), aged 33,8±11,4years with CHD (TGA, UVH, Ebstein's anomaly, ccTGA, Eisenmenger syndrome, DORV, CAT, unoperated and operated ToF) underwent MTWA, ECG, 24h Holter ECG, BNP assessment and cardiopulmonary exercise test. Control group: 45 adults age- and sex-matched. MTWA classification: normal: negative (-) and abnormal: positive (+) and indeterminate (ind). Due to similar prognostic significance tests classified as MTWA(+) and MTWA(ind) were combined into non-negative(non-) group. VA classification: malignant- sustained ventricular tachycardia (sVT), potentially malignant- non-sustained ventricular tachycardia (nsVT) and >10 premature ventricular complexes per hour (PVC/h). Results: 31P were MTWA(+), 53P MTWA(ind) and 120P MTWA(-). Due to excessive noise 25P were excluded. MTWA(non-) was more frequent in study group vs. controls (p=0,000001). The highest ratio of MTWA(non-) was in Eisenmenger syndrome (87,5%). Among patients with MTWA(non-) malignant and potentially malignant VA was more frequent compared to MTWA(-) (p=0,003; p=0,016, respectively). Male gender and pulmonary hypertension (PH) were more often in MTWA(non-) vs. MTWA(-) (p=0,0049; p=0,00007, respectively). MTWA(non-) compared to MTWA(-) had lower: blood saturation (p=0,000295), maximal oxygen consumption (peakVO2) (p=0,002) and VE/VCO2slope (p=0,012). MTWA(non-) vs. MTWA(-) had higher: BNP values (p=0,0306) and NYHA class (p=0,007). Factors increasing MTWA(non-) incidence are: in univariate logistic regression: PH (OR=24,29), sVT (OR=7,31), VA (OR=3,01), male gender (OR=2,61), NYHA>I (OR=2,06), worse VE/VCO2slope (OR=1,07) and peakVO2 fall (OR=0,92); in multivariate logistic regression: PH (OR=14,16), male gender (OR=10,2), worse VE/VCO2slope (OR=1,06) and peakVO2 fall (OR=0,89). Conclusions: In adults with CHD abnormal MTWA occurs more often than in healthy population. Probability of this phenomenon increases in patients with malignant ventricular arrhythmia and clinical findings possibly related to lethal arrhythmia including advanced heart failure and pulmonary hypertension. Incidence of abnormal MTWA is higher in men. MTWA might be of potential role in SCD risk stratification in adults with congenital heart diseases.

Clinical use of microvolt T-wave alternans in patients with depressed left ventricular function eligible for ICD implantation: mortality outcomes after long term follow-up

Implantable cardioverter-defibrillators (ICDs) reduce mortality in patients with left ventricular dysfunction. However, left ventricular dysfunction alone has significant limitations as a risk stratifier for guiding ICD therapy [1,2]. In the SCD-HeFT trial [3], the ICDmediated reduction in absolute mortality was 1.4% per year (7.2% over 5 years) indicating that only a very small fraction of patients with ICDs actually receive life saving therapy from the devices. Moreover, ICD implantation [4] is associated with a high rate of subsequent complications suchas infections, inappropriate shocks, leadand generator failures and recalls. Consequently there is a need to more accurately identify those individuals who will benefit from ICD implantation. Microvolt T-wave alternans (MTWA) has been linked mechanistically to the development of ventricular tachyarrhythmias [5] and is a clinical marker of increased risk of sudden cardiac death (SCD) [6–8]. Conversely, patients with a negative MTWA test have a very low risk of SCD [8]. In our departmentwe routinely measureMTWA in patients without a history of cardiac arrest being considered for prophylactic ICD implantation [9] and the result is a major determinant of the decision of whether or not to implant an ICD. From 2001 to March 2011 MTWA tests were performed on 178 consecutive patients with ischemic and non-ischemic cardiomyopathy who were eligible for ICD implantation according to clinical guidelines in place at the time of evaluation. Patientswith a normal testwere offered the option to not receive an ICD. We conducted long-term follow-up of these patients. The primary endpointwas defined as all-causemortality and the secondary endpoint was defined as cardiac mortality. Patients underwent an MTWA exercise bicycle testing that was interpreted both automatically within the HearTwave system and by two expert readers. Because patients with positive and indeterminate MTWA tests results display elevated event rates [8], all comparisons in this analysis were made between patients with normal (negative) and abnormal (positive or indeterminate) MTWA tests. The baseline characteristics of the 178 patients are listed in Table 1. All participantswere in NewYorkHeart Association functional class II or III and had left ventricular ejection fraction ≤ 40% (mean 30 ± 6). The MTWAabnormal patients compared to theMTWAnormal patients, on a statistically univariate basis, had higher NYHA class, wider QRS, and lower LVEF.MTWAwasabnormal in129 (72%)andnormal in49patients (28%). Substantially fewer patients (15/49, 31%) in the MTWA normal group received an ICD than did patients in the MTWA abnormal group (103/129, 80%), p = 0.0001. During the follow-up (median 64 months) a total of 35 deaths occurred. In the MTWA normal group 4 patients died – all of noncardiac cause; in the MTWA abnormal group 31 deaths occurred and were classified as follows: 20 cardiac deaths, 7 non-cardiac and 4 unknown.

Abstract 9967: Microvolt T-wave Alternans in Adults with the Chosen Forms of Congenital Heart Disease

Introduction. Sudden cardiac death (SCD) in adults with congenital heart diseases (CHD) is usually caused by ventricular arrhythmia (VA). Among the noninvasive methods of risk stratification for SCD is microvolt T-wave alternans (MTWA), reflecting repolarization inhomogeneity. We sought to determine the incidence of MTWA among adults with chosen forms of CHD as well as its coincidence with VA and other findings presumably associated SCD. Methods and Results. The study group: 102P with CHD characterized by pathology within right ventricle or single ventricle physiology (transposition of the great arteries after atrial switch, univentricular heart, Ebstein’s anomaly, congenitally corrected transposition of the great arteries, Eisenmenger syndrome, double-outlet right ventricle, common arterial trunk, unoperated tetralogy of Fallot). Controls: 45 volunteers age and sex-matched. All subjects underwent spectral MTWA test, ambulatory ecg monitoring, cardiopulmonary test, BNP assessement. MTWA positive and indeterminate were labeled ‘abnormal’ and were present more often in the study group, compared to controls (39,2% vs 2,3%, p=0,00001). Among subjects with abnormal MTWA sustained ventricular tachycardia (sVT) was observed more often compared to MTWA(-): 19,4% vs 3,6%, p=0,026. The patients with abnormal MTWA had a lower blood saturation (p=0,047), more often were males (p=0,031), had higher NYHA class (p=0,04), worse cardiopulmonary parameters: %PeakVO2 (p=0,034), %HRmax (p=0,003). Factors associated with abnormal MTWA: sVT (OR=20,7 p=0,037), male gender (OR=15,9 p=0,001) in multivariate regression; in univariate analysis: male gender (OR=2,7, p=0,021), presence of VA (OR=2,6, p=0,049), NYHA &gt; I (OR=2,06, p=0,033), %HRmax, %PeakVO2, VE/VCO2 slope (OR=0,94, p=0,005; OR=0,97, p=0,042; OR=1,05, p=0,037). Conclusions. The abnormal MTWA occurs significantly more often in adults with the chosen forms of CHD than among healthy subjects. The probability of abnormal MTWA increases in patients with malignant VA, in males and among subjects with heart failure and cyanosis. MTWA might be of potential role in risk stratification for SCD.

MICROVOLT T-WAVE ALTERNANS AS A PREDICTOR OF MORTALITY AND SEVERE ARRHYTHMIAS IN PATIENTS WITH CARDIAC DYSFUNCTION

ObjectivesOur previous study shows that Microvolt T-wave alternans (MTWA) testing has significant value for the prediction of mortality or severe arrhythmic events in a population of individuals with implanted ICDs....

Predictive Value of Microvolt T-Wave Alternans for Cardiac Death or Ventricular Tachyarrhythmic Events in Ischemic and Nonischemic Cardiomyopathy Patients: A Meta-Analysis

Microvolt T-wave alternans (MTWA) has been proposed as a predictor of the risk of ventricular tachyarrhythmias (VT) and sudden cardiac death (SCD). Aim of this study was to perform a systematic review of the literature and a meta-analysis of MTWA in primary prevention patients with ischemic and nonischemic cardiomyopathy. The positive predictive value (PPV), negative predictive value (NPV), and relative risk (RR) of MTWA in predicting death, cardiac death, and SCD during follow-up were reported. Fifteen studies involving 5681 patients (mean age 62 years, mean ejection fraction 32%) were included. The summary PPV during the average 26-month follow-up was 14% (95% CI: 13-15); NPV was 95% (95% CI: 94-96), and the univariate RR was 2.35 (95% CI: 1.68-3.28). The predictive value of MTWA was similar in patients with ischemic and nonischemic cardiomyopathy. The average RR for SCD or VT events of an abnormal MTWA was 2.40, similar to that for cardiac death. When we grouped the studies together depending upon whether beta-blockers were withheld prior to MTWA screening, the beta-blockers group showed an RR of 5.88. By contrast, the group in which beta-blocker therapy was withheld had an RR of 1.63. A positive MTWA determined an approximately 2.5-fold higher risk of cardiac death and life-threatening arrhythmia and showed a very high NPV both in ischemic and nonischemic patients. An abnormal MTWA test was associated with a 5-fold increased risk for cardiac mortality in the low-indeterminate group and about a 6-fold increased risk in beta-blockers group.

Relationship Between Early Diastolic Dysfunction and Abnormal Microvolt T-Wave Alternans in Patients With Type 2 Diabetes

Abnormal microvolt T-wave alternans (MTWA), a marker of ventricular arrhythmic risk, is a highly prevalent condition in patients with type 2 diabetes mellitus (T2DM) and is correlated with glycemic control. However, there is uncertainty as to whether central or peripheral hemodynamic factors are associated with abnormal MTWA in T2DM individuals. We studied 50 consecutive, well-controlled T2DM outpatients without a history of ischemic heart disease and with normal systolic function. All patients underwent a complete echocardiographic Doppler evaluation with spectral tissue Doppler analysis. MTWA analysis was performed noninvasively during submaximal exercise. Effective arterial elastance, arterial compliance, and heart rate variability were also measured. Compared with patients with MTWA negativity (n = 38), those with MTWA abnormality (n = 12, 24%) had significantly lower e' (7.6 ± 1.3 versus 9.1 ± 1.7 cm/s; P < 0.01), a' (10.2 ± 1.6 versus 12.7 ± 1.9 cm/s; P < 0.001) and s' velocities (8.7 ± 1.1 versus 10.2 ± 1.5 cm/s; P = 0.001) and higher indexed left ventricular mass (121.3 ± 16.4 versus 107.5 ± 16.5 g/m2; P = 0.016), indexed left atrial volume (33.5 ± 11.9 versus 23.6 ± 5.6 mL/m2; P < 0.001), and E/e' ratio (8.8 ± 1.4 versus 6.5 ± 1.3; P < 0.001). Multivariable logistic regression analysis revealed that higher E/e' ratio was the only independent correlate of abnormal MTWA (adjusted odds ratio, 3.52; 95% confidence interval, 1.19 to 10.6; P = 0.02) after controlling for glycemic control and other potential confounders. In this pilot study, we found that early diastolic dysfunction, as measured by tissue Doppler imaging, is independently associated with MTWA abnormality in T2DM individuals with normal systolic function. Further larger studies are needed to examine the reproducibility of these results.

Microvolt T-Wave Alternans in End-Stage Renal Disease Patients—Associations with Uremic Cardiomyopathy

Premature cardiovascular (CV) events, especially sudden cardiac death, are common in ESRD patients and associated with uremic cardiomyopathy. Identification of high-risk patients is difficult. Microvolt T-wave alternans (MTWA) is a noninvasive method of detecting variability in electrocardiogram (ECG) T-wave morphology and is a promising technique for identifying patients at high risk of ventricular tachyarrhythmias. MTWA results of ESRD and hypertensive left ventricular hypertrophy (LVH) patients were assessed to determine the prevalence of abnormal results and associations with uremic cardiomyopathy. In this single-center observational study, 200 ESRD and 30 LVH patients underwent assessment including CV history, ECG, cardiac magnetic resonance imaging, and an MTWA exercise test. MTWA results were classified as "negative" or "abnormal" on the basis of previously published reports. An abnormal MTWA result was more common in ESRD compared with LVH patients (57.5% versus 26.7%, respectively; P = 0.002). In ESRD patients, MTWA was significantly associated with uremic cardiomyopathy, clinical history of atherosclerosis (coronary, cerebral, peripheral) and diabetes mellitus, older age, and hemodialysis therapy. Independent associations with an abnormal MTWA result were older age, macrovascular disease, increased left ventricle (LV) mass, and LV dilation. Features of uremic cardiomyopathy are associated with an abnormal MTWA result.

Do Beta‐Blockers Impact Microvolt T‐Wave Alternans Testing in Patients at Risk for Ventricular Arrhythmias? A Meta‐Analysis

Results of microvolt T-wave alternans (MTWA) studies vary and may be influenced by whether beta-blocker therapy was withheld prior to MTWA assessment. We conducted a meta-analysis of the predictive value of MTWA screening for ventricular arrhythmic events in primary prevention patients with left ventricular dysfunction and examined whether results differed depending upon whether beta-blocker use was withheld prior to MTWA testing. Prospective studies that evaluated whether MTWA predicted ventricular arrhythmic events published between January 1980 and September 2008 were identified. Summary estimates for the predictive value of MTWA were derived with random-effects models. Nine studies involving 3,939 patients were identified. Overall, an abnormal MTWA (positive and indeterminate) test was associated with an almost 2-fold increased risk for arrhythmic events (pooled RR = 1.95, 95% CI: 1.29-2.96; P = 0.002). However, significant heterogeneity across studies was observed (P = 0.024). In the 4 studies in which beta-blocker therapy was not withheld prior to MTWA assessment, an abnormal MTWA test was associated with a 5-fold increased risk for arrhythmic events (pooled RR = 5.39, 95% CI: 2.68-10.84; P < 0.001) and was robust to sensitivity analyses. In contrast, the association was much weaker in those studies where the use of beta-blocker therapy was withheld prior to MTWA testing (pooled RR = 1.40, 95% CI: 1.06-1.84; P = 0.02). In primary prevention patients with left ventricular dysfunction, the predictive power of MTWA varied widely, based on whether beta-blocker therapy was withheld prior to its assessment. This observation may explain the inconsistent results of MTWA studies in this population.

005 Action potential amplitude alternans and ventricular arrhythmia in a rabbit model of heart failure

Introduction In recent large studies abnormal microvolt T-wave alternans has failed to predict arrhythmic events, raising the possibility that it is not specifically associated with a pro-arrhythmic substrate. Although discordant repolarisation alternans has been mechanistically linked to re-entrant ventricular fibrillation (VF) in experimental models and alternans has been demonstrated to occur in pacing-induced heart failure, whether a mechanistic link between alternans and VF in heart failure is unknown. The aim of this study was therefore to examine the occurrence of repolarisation alternans in a rabbit model of heart failure and to investigate the link between alternans and in VF failing hearts. Methods Heart failure was induced by coronary arterial ligation (n=11). Hearts from normal (n=12) and sham-operated rabbits (n=4) were used as controls. Rabbits were killed with an intravenous injection of 200 mg pentobarbital sodium. Hearts were excised and the left coronary artery was cannulated and perfused with oxygenated Tyrode9s solution maintained at pH7.4 and 37 (n=15) or 30°C (n=16). Perfused left ventricular (LV) wedge preparations were dissected, loaded with voltage-sensitive dye and paced from the endocardium. An optical mapping system was used to record transmural optical action potentials (APs) during a progressive reduction in pacing cycle length (CL). Data analysis was performed using custom software employing standard algorithms. Results Repolarisation alternans and ventricular arrhythmia were significantly more common in failing hearts at each temperature. Heart failure was not associated with an increased incidence of transmural discordant alternans. Progressive alternans of AP amplitude was observed during rapid pacing and was associated with both transmural conduction block and inducibility of VF.Abstract 005 Figure 1 A compares alternans of AP duration (APD) and AP amplitude in two failing hearts, one which developed VF during rapid pacing and the other which did not. In both hearts, APD alternans of a similar magnitude was present and in the VF prone heart, APD alternans was accompanied by marked alternans of AP amplitude. By contrast, in the VF resistant heart APD alternans was seen in isolation, without any significant alternans in AP amplitude. The mean magnitude of APD and AP amplitude alternans at the shortest CL captured during rapid pacing protocols as a function of mean pacing cycle length is shown in Figure B. The magnitude of relative AP amplitude alternans is greater than that of APD alternans. Although the magnitude of APD alternans was similar in VF prone and VF resistant hearts, the magnitude of AP amplitude alternans was greater in VF prone hearts. Conclusions For the first time we describe the development of progressive changes in AP amplitude during alternans, and their relation to the development of conduction block. The data suggest an important role for amplitude alternans in the development of arrhythmias in failing hearts.

Microvolt T-Wave Alternans, Peak Oxygen Consumption, and Outcome in Patients with Severely Impaired Left Ventricular Systolic Function

Abnormal microvolt T-wave alternans (MTWA) and low peak oxygen consumption (VO2) both predict poor outcome in heart failure. However, their independent predictive properties have not been assessed in large-scale cohorts. This was an observational prospective cohort study of 303 consecutive patients referred for metabolic stress testing. All had an ejection fraction < or = 40% and were considered candidates for transplantation. The exercise laboratory did not collect MTWA data from patients with implanted pacemakers or defibrillators. The primary end point was a composite of all-cause death or United Network for Organ Sharing status 1 transplantation. During a 2.8-year period, there were 34 deaths and 17 transplantations. Patients with abnormal MTWA had a higher event rate of 23% (31 of 136) vs 12% (20 of 167), with an unadjusted hazard ratio (HR) of 1.90 (95% confidence interval [CI], 1.90-3.33; p = 0.03). The association remained significant after adjustment for 3 clinical variables (HR, 1.89; 95% CI, 1.05-3.39; p = 0.03). After adding peak VO2 to the model, the association was no longer significant (adjusted HR, 1.18; 95% CI, 0.64-2.17, p = 0.60). After accounting for peak VO2 and 28 other confounders in a matched propensity analysis, MTWA was not predictive (propensity-matched HR, 0.79; 95% CI, 0.37-1.66; p = 0.53). These results confirm the association of abnormal MTWA with poor outcome amongst patients with impaired left ventricular systolic function. However, this association is markedly attenuated after accounting for peak VO2.

Clinical Assessment of the Risk for Sudden Cardiac Death in Patients with Sickle Cell Anemia

Previous studies suggest that patients with sickle cell anemia (SCA) have an increased risk of sudden cardiac death; however, its etiology and mechanism are not well defined. Left ventricular hypertrophy (LVH), ventricular tachycardia (VT) and poor left ventricular systolic function are known risk factors for sudden cardiac death. An abnormal microvolt T-wave alternans (TWA) test is also a predictor of sudden cardiac death risk, but it has not been applied to this patient population. We performed a 12-lead electrocardiogram, 24-hour Holter monitor, two-dimensional echocardiogram, nuclear stress test and microvolt TWA test to determine whether markers of sudden cardiac death could be identified. Twenty-six patients were evaluated with a mean age of 40 +/- 12 years. The two-dimensional echocardiogram revealed a normal ejection fraction in 23 patients and LVH in 17 (65%), whereas hypertension was noted in only five (19%). Microvolt TWA testing was abnormal in six of 22 patients (27%). Holter monitor revealed VT in two patients. Among the clinical variables tested, only LVH was predictive of an abnormal TWA test. The sensitivity, specificity, positive and negative predictive value of LVH for and abnormal TWA test was 100, 56, 46 and 100%. LVH was common in patients with SCA and disproportional to the number of patients with hypertension. Microvolt TWA tests were abnormal in 27% of patients; however, LVH was the only clinical variable that predicted an abnormal TWA test. Risk stratification of SCA patients may require echocardiographic detection of LVH and an abnormal TWA test due to the high negative predictive value. The significance of an abnormal TWA test should be further evaluated in a large study, with a longer follow-up period.

Relationship Between Abnormal Microvolt T‐Wave Alternans and Poor Glycemic Control in Type 2 Diabetic Patients

Abnormal microvolt T-wave alternans (TWA) predicts the risk of ventricular arrhythmias and sudden cardiac death. Although type 2 diabetes is associated with an increased risk of these events, there is a dearth of available data on microvolt TWA measurements in type 2 diabetic populations. We studied 59 consecutive type 2 diabetic outpatients without manifest cardiovascular disease (CVD) and 35 non-diabetic controls who were matched for age, sex, and blood pressure values. Microvolt TWA analysis was performed non-invasively using the CH-2000 system during a sub-maximal exercise with the patient sitting on a bicycle ergometer. The frequency of abnormal TWA was significantly higher in diabetic patients than in controls (25.4 vs 5.7%; P < 0.01). Among diabetic patients, those with abnormal TWA (n = 15) had remarkably higher hemoglobin A1c (HbA1c) (8.1 +/- 0.9 vs 7.1 +/- 0.8%, P < 0.001) and slightly smaller time-domain heart rate variability parameters (i.e., RMSSD, root mean square of difference of successive R-R intervals) than those with normal TWA (n = 44). Gender, age, body mass index, lipids, blood pressure values, cigarette smoking, diabetes duration, microvascular complication status, QTc interval, and current use of medications did not significantly differ between the groups. In multivariate regression logistic analysis, HbA1c (OR 13.6, 95% CI 2.0-89.1; P = 0.0076) predicted abnormal TWA independent of RMSSD values and other potential confounders. Our findings suggest that abnormal TWA is a very common condition (approximately 25%) among people with type 2 diabetes without manifest CVD and is closely correlated to glycemic control.

T‐Wave Alternans: Is It an Appropriate Test for Primary Prevention Implantable Cardioverter‐Defibrillator Risk Stratification?

Abstract. Background. Several randomized controlled trials have demonstrated benefit for implantable cardio-verter-defibrillator (ICD) prophylaxis in selected patients. However, the absolute benefit of ICD prophylaxis on mortality is relatively small (5.6% or 7.2%) in patients selected using left ventricular ejection fraction (LVEF).1 Thus, only a few of the ICDs implanted prophylactically ever deliver appropriate therapy. The Center for Medicare & Medicaid Services (CMS) has accepted the scientific validity of these ICD prophylaxis trials, but has recognized the need for better risk stratification because the inconvenience, adverse effects, and cost of implanting ICDs in all patients who meet the criteria are substantial. Microvolt T-wave alternans (MTWA) testing can identify patients at increased risk of sudden cardiac death. The results of a study dealing with the use of MTWA in patients with either ischemic heart disease or nonischemic cardiomyopathy and LVEF ≤0.40 have recently been published. Methods. The study hypothesized that MTWA improves the selection of patients for ICD prophylaxis, especially by identifying patients who are not likely to benefit. The study was conducted at 11 clinical centers in the United States. Patients were eligible if they had an LVEF ≤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 (NYHA) functional class IV heart failure. Participants underwent an MTWA test and then were followed for approximately 2 years. The primary outcome was all-cause mortality or nonfatal 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 nonfatal sustained ventricular arrhythmias) occurred. Comparing patients with normal and abnormal MTWA tests, the hazard ratio for the primary end point was 6.5 at 2 years (95% confidence interval. 2.4–18.1; p<0.001). Survival of patients with normal MTWA tests was 97.5% at 2 years. The strong association between MTWA and the primary end point was similar in all subgroups tested. Conclusions. The authors concluded that among patients with heart disease and LVEF ≤0.40, MTWA can identify not only a high-risk group, but also a low-risk group unlikely to benefit from ICD prophylaxis.—Bloomfield DM, Bigger JT, Steinman RC, et al. Microvolt T-wave altemans and the risk of death or sustained ventricular arrhythmias in patients with left ventricular dysfunction. J Am Coll Cardiol. 2006;47:456–463. Comment. The MTWA test, widely seen as a potential way to screen out patients who meet reimbursement criteria for primary-prevention ICD therapy, but probably won't ever need it, appeared to live up to that hope in this well designed study. MTWA is a simple test that monitors beat-to-beat microvolt-level variations in the shape of the electrocardiographic T wave during exercise stress. The MTWA is a simple, relatively inexpensive, noninvasive test that can be done routinely in a doctor's office using modifications of currently available exercise testing equipment. This study strongly suggests that MTWA testing can identify a large group of patients with left ventricular dysfunction who have an excellent prognosis and are unlikely to benefit from ICD prophylaxis. The investigators followed 549 patients with an LVEF ≤0.40 and no history of sustained ventricular arrhythmia, 66% of whom had tested positive for T-wave alternans. Most of the patients were in NYHA class II or III heart failure; the average LVEF was 0.25. Over a follow-up of up to 2 years, averaging 20 months, the one third of patients with normal baseline MTWA findings had a 2-year survival of 97.5%. The 11 instances of nonfatal sustained ventricular arrhythmias and 40 deaths were highly concentrated among those who had been MTWA-abnormal. Although LVEF wasn't predictive of such events in multivariate analysis, baseline MTWA emerged as a highly significant risk factor. As if to emphasize MTWA's potential risk-stratification advantage, the test identified a low-risk group among patients considered at especially high risk by conventional criteria. The 2-year event rate was 11.8% among those with an LVEF of 0.31–0.40 and an abnormal MTWA, but it was only 3.5% for an LVEF ≤0.30 with a normal MTWA. Based on MADIT-II2 and SCD-HeFT,3 according to the authors, about 18 or 14 ICDs, respectively, must be implanted to save one life. According to the current analysis, exclusion of lower-risk patients using the MTWA test would drop the number of implanted ICDs per life saved to seven. This improvement in numbers needed to treat to save one life can have a very substantial effect on the modern practice of cardiology, especially if one considers the economic factors. Will the medical community adopt this trial immediately, or wait while MTWA is being confirmed in other trials? Only time will tell.

Microvolt T-Wave Alternans and the Risk of Death or Sustained Ventricular Arrhythmias in Patients With Left Ventricular Dysfunction

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. 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. 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. 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. 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.

Microvolt T-Wave Alternans for the Risk Stratification of Ventricular Tachyarrhythmic Events: A Meta-Analysis

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. Previous studies describing the use of MTWA as a predictor of ventricular tachyarrhythmic events have been limited by small sample sizes and disparate populations. 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. 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). 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.