Microvolt T-wave Alternans Testing Research Articles

Prognostic Evaluation of Microvolt T-Wave Alternans in Hypertrophic Cardiomyopathy: 9-year Clinical Follow-up.

Sudden cardiac death (SCD) resulting from ventricular arrhythmia is the main complication of hypertrophic cardiomyopathy (HCM). Microvolt T-wave alternans (MTWA) is associated with the occurrence of ventricular arrhythmias in several heart diseases, but its role in HCM remains uncertain. To evaluate the association of MTWA with the occurrence of SCD or potentially fatal ventricular arrhythmias in HCM patients in a long-term follow-up. Patients diagnosed with HCM and NYHA functional class I-II were consecutively selected. At the beginning of the follow-up, the participants performed the MTWA evaluation using the modified moving average during the stress test. The results were classified as altered or normal. The composite endpoint of SCD, ventricular fibrillation, sustained ventricular tachycardia (SVT) or appropriate implantable cardiac defibrillation (ICD) therapy was assessed. The level of significance was set at 5%. A total of 132 patients (mean age of 39.5 ± 12.6 years) were recruited and followed for a mean of 9.5 years. The MTWA test was altered in 74 (56%) participants and normal in 58 (44%). Nine events (6.8%) occurred during the follow-up, with a prevalence of 1.0%/year - six SCDs, two appropriate ICD shocks and one episode of (SVT). Altered MTWA was associated with non-sustained ventricular tachycardia on Holter (p = 0.016), septal thickness ≥30 mm (p < 0.001) and inadequate blood pressure response to effort (p = 0.046). Five patients with altered MTWA (7%) and four patients with normal MTWA (7%) had the primary outcome [OR = 0.85 (95% CI: 0.21 - 3.35, p=0.83)]. Kaplan-Meir event curves showed no differences between normal and altered MTWA. Altered MTWA was not associated with the occurrence of SCD or potentially fatal ventricular arrhythmias in HCM patients, and the low rate of these events during long-term follow-up suggests the good prognosis of this heart disease.

Microvolt t-wave alternans its clinical significance in the assessment of the risk of sudden cardiac death among patients with hypertrophic cardiomyopathy

Abstract Summary Some patients with hypertrophic cardiomyopathy (HCM) are at significant risk of premature sudden death. Identification of the risk factors may enable effective prevention of adverse cardiac events in these patients. Assessment of the microvolt T-wave alternans (MTWA) is a recognized non-invasive diagnostic test used in risk stratification of sudden cardiac death (SCD). However, the number of reports on the frequency of occurrence of MTWA in HCM is small. Aim: Evaluation of the prognostic value of MTWA in predicting the risk of arrhythmic events (sudden cardiac death, documented VT/VF, appropriate ICD discharge) in patients with HCM. Material and methods 122 patients with HCM underwent detailed clinical assessment and ECG- and echocardiographic examination. They underwent 24-hour ambulatory ECG monitoring, and the following elements were analysed: 1) arrhythmias, 2) heart rate variability (HRV) and the QT segment, 3) the presence of ventricular late potentials (LP), 4) heart rate turbulence (HRT). MTWA assessment was made during a test on a treadmill (Cambridge Heart). In accordance with the adopted criteria, the test was interpreted as negative, positive or indeterminate. Subsequently, positive and indeterminate results were described collectively as MTWA(+) and negative results as MTWA(−). Then the patients were divided into two groups: Group 1 – 57 patients (46,7%) with MTWA(−), and Group 2 – 65 patients (53,2%) with MTWA(+). In order to stratify the risk, the following were adopted as composite primary endpoints: sudden cardiac death or hospitalization for life-threatening arrhythmias (VT/VF), and appropriate ICD discharge. Results The mean follow-up period of the patients was 57±8 months; during that time, events that met the criteria for the endpoint occurred in 16 patients. On the basis of univariate analysis, 10 variables with a significant influence on the occurrence of an event were selected (unexplained syncope, NT-proBNP values elevated above 411 pg/ml, size of the left atrium over 44mm, diastolic thickness of the interventricular septum over 25 mm, the presence of MTWA(+), the QRS width &amp;gt;90 msec, QTc &amp;gt;467 msec, QTd &amp;gt;70 msec, SDNN &amp;lt;110 msec, and sinus rhythm turbulence parameters TS &amp;lt;2,9 ms/2RR). These variables were then included in a multivariate analysis. The model from a Cox regression analysis showed that the presence of unexplained syncope (HR=1,4), MTWA(+) (HR=1,5), size of the left atrium over 44mm (HR=5), and the thickness of the interventricular septum over 25 mm (HR=1,5) increased the risk of sudden events. Conclusions 1) Patients with hypertrophic cardiomyopathy had a significant percentage of positive results of the microvolt T-wave alternans test (MTWA+), 2) Positive MTWA test result in patients with hypertrophic cardiomyopathy can help to identify patients at risk of sudden cardiac death. Funding Acknowledgement Type of funding sources: None.

Repeating noninvasive risk stratification improves prediction of outcome in ICD patients.

BackgroundNoninvasive risk stratification aims to detect abnormalities in the pathophysiological mechanisms underlying ventricular arrhythmias. We studied the predictive value of repeating risk stratification in patients with an implantable cardioverter‐defibrillator (ICD).MethodsThe EUTrigTreat clinical study was a prospective multicenter trial including ischemic and nonischemic cardiomyopathies and arrhythmogenic heart disease. Left ventricular ejection fraction ≤40% (LVEF), premature ventricular complexes >400/24 hr (PVC), non‐negative microvolt T‐wave alternans (MTWA), and abnormal heart rate turbulence (HRT) were considered high risk. Tests were repeated within 12 months after inclusion. Adjusted Cox regression analysis was performed for mortality and appropriate ICD shocks.ResultsIn total, 635 patients had analyzable baseline data with a median follow‐up of 4.4 years. Worsening of LVEF was associated with increased mortality (HR 3.59, 95% CI 1.17–11.04), as was consistent abnormal HRT (HR 8.34, 95%CI 1.06–65.54). HRT improvement was associated with improved survival when compared to consistent abnormal HRT (HR 0.10, 95%CI 0.01–0.82). For appropriate ICD shocks, a non‐negative MTWA test or high PVC count at any moment was associated with increased arrhythmic risk independent of the evolution of test results (worsening: HR 3.76 (95%CI 1.43–9.88) and HR 2.50 (95%CI 1.15–5.46); improvement: HR 2.80 (95%CI 1.03–7.61) and HR 2.45 (95%CI 1.07–5.62); consistent: HR 2.47 (95%CI 0.95–6.45) and HR 2.40 (95%CI 1.33–4.33), respectively). LVEF improvement was associated with a lower arrhythmic risk (HR 0.34, 95%CI 0.12–0.94).ConclusionsRepeating LVEF and HRT improved the prediction of mortality, whereas stratification of ventricular arrhythmias may be improved by repeating LVEF measurements, MTWA and ECG Holter monitoring.

Abstract 16953: Prospective Negative Microvolt T-Wave Alternans Testing is a Marker for Lower Risk of Cardiovascular Death and Appropriate Shock Therapy

Introduction: Microvolt T-wave alternans (MTWA) refers to a pattern of beat-to-beat oscillations in T-wave morphology. Hypothesis: We hypothesized that patients with negative MTWA testing were at decreased risk for cardiovascular death and appropriate shock therapy. Methods: We studied 913 patients from a prospective international registry from Europe, Asia and USA (9 centers total). All recruited patients qualified for primary prevention of sudden cardiac death with ICD or CRT-D. Beta-blockers were discontinued prior to MTWA testing. We used best-subsets analysis of our study population to identify predictors of all-cause mortality. Ten clinical and demographic variables were included in the analysis. We then used these predictors to evaluate the predictive capacity of MTWA in a multivariate model. Results: The mean follow-up was 4.0 ± 3.0 years, mean age was 69.5 ± 12.5 years, 84% were male, and 63% had ischemic cardiomyopathy. 52% and 11% of patients received ICD and CRT-D, respectively. LVEF &lt;25% (HR 2.17, p&lt;0.001), NYHA class&gt;II (HR 1.75, p=0.01) and use of diuretics (HR 2.64, p&lt;0.001) were significantly associated with all-cause mortality in a multivariate model. Using this multivariate model, a negative MTWA outcome was not associated with all-cause mortality (HR 0.95, p=0.80), however a negative MTWA outcome was associated with the risk of cardiovascular death (HR 0.40, p=0.01) and the combined endpoint of cardiovascular death and ICD-rendered shock therapy (HR 0.28, p&lt;0.001). This was consistent in both ischemic and nonischemic cardiomyopathy (p value for interaction=0.999). Conclusions: These findings suggest that non-negative MTWA testing is indicative of an underlying arrhythmogenic substrate, manifested as cardiovascular death and appropriate shock therapy. MTWA testing can provide further information for patient selection for ICD placement. Figure 1 . Kaplan-Meier Curve demonstrating the time-dependent endpoint of cardiovascular death. The follow-up time displayed on this graph is measured in days.

TWARMI pilot trial: The value and optimal criteria of microvolt T-wave alternans in the diagnosis of reversible myocardial ischemia in patients without structural cardiac disease.

Microvolt T-wave alternans (MTWA) testing is a beat-to-beat fluctuation in the amplitude of T wave. We investigated whether: (a) MTWA can be new non-invasive tool for detection of reversible ischemia in patients with suspected CAD without structural heart disease, (b) MTWA can detect ischemia earlier and with greater test accuracy compared with exercise ECG ST-segment testing, and (c) threshold value of MTWA and heart rate at which the alternans is estimated can be different compared to standard values. A total of 101 patients with suspected stable coronary disease, but without structural heart disease, were included. Echocardiography, exercise ECG test, MTWA with classical and modified threshold alternans values, and coronary angiography were performed. About 33.3% patients had a false-positive result on exercise ECG test. The sensitivity of exercise ECG ST-segment test in the detection of coronary artery disease was 97.8%, and the specificity was 42.5% (DOR 33.89). In a group of angiographically positive patients, standard MTWA accurately identified 60% of patients, while 40% had a false-negative result. About 91.8% patients with negative angiography result were accurately identified with 8.2% false positives. The sensitivity of MTWA was 59.61% and specificity 91.83%. Best ratio of sensitivity and specificity (86.53% and 95.91%, DOR 151.06) had modified criteria for positive MTWA (MTWA >1.5µV at heart rate 115-125/min). This study showed that MTWA can be the new non-invasive tool for the detection of reversible ischemia in patients with suspected CAD without structural heart disease. Also, MTWA can detect ischemia earlier and with greater accuracy compared with exercise ECG testing.

Predictors of poor outcome in patients with pulmonary arterial hypertension: A single center study.

ObjectivesPulmonary arterial hypertension (PAH) is a rare disorder with unfavorable prognosis despite implementation of specific PAH-oriented therapy. The aim of the study was to define predictors of poor prognosis in patients from one center treated according to the Polish National Health Fund program.Patients and methodsForty-seven consecutive patients (30 women; aged 39±17 years) with PAH diagnosis were enrolled to the study. Clinical assessment, laboratory measurements, electrocardiogram, echocardiography, 6-minute walk test, 24-hour Holter monitoring, cardiopulmonary exercise test and microvolt T-wave alternans test were performed during routine visits. Eight patients died during 2.6±1.7 years follow-up.ResultsParametrs which differentiated patients who died were brain natriuretic peptide (BNP) concentration ≥330 pg/mL (sensitivity 88%, specificity 92%, area under the ROC curve [AUC] 0.92); bilirubin concentration ≥1.2 mg/dL (sensitivity 88%, specificity 81%, AUC 0.85); right atrial area ≥21 cm2 (sensitivity 86%, specificity 69%, AUC 0.84), right ventricular (RV) dimension in the apical 4-chamber view ≥47 mm (sensitivity 86%, specificity 86%, AUC 0.85) and RV to left ventricular diastolic diameter ratio ≥1.5 (sensitivity 83%, specificity 84%; AUC 0.85). In multivariate analysis, independent predictors of mortality were higher BNP (p = 0.04) and bilirubin level (p = 0.03), higher right atrial area (p = 0.02) and lower tricuspid annular plane systolic excursion (p = 0.03).ConclusionsIn PAH patients treated with specific PAH-oriented therapy right atrial enlargement, impaired right ventricular systolic function, as well as increased BNP and bilirubin concentration was associated with an increased mortality risk.

Association between Microvolt T-Wave Alternans and Malignant Ventricular Arrhythmias in Chagas Disease.

BackgroundSudden cardiac death is the most frequent death mechanism in Chagas disease, responsible for 55% to 65% of the deaths of patients with chronic Chagas cardiomyopathy (CCC). The most often involved electrophysiological mechanisms are ventricular tachycardia and ventricular fibrillation. The implantable cardioverter defibrillator (ICD) has a beneficial role in preventing sudden death due to malignant ventricular arrhythmias, and, thus the correct identification of patients at risk is required. The association of microvolt T-wave alternans (MTWA) with the appearance of ventricular arrhythmias has been assessed in different heart diseases. The role of MTWA is mostly unknown in patients with CCC.ObjectivesTo evaluate the association between MTWA and the occurrence of malignant ventricular arrhythmias in patients with CCC. MethodThis is a case-control study including patients with CCC and ICD, with history of malignant ventricular arrhythmias (case group), and patients with CCC and no history of those arrhythmias (control group). The MTWA test results were classified as negative and non-negative (positive and indeterminate). The significance level adopted was a = 0.05.ResultsWe recruited 96 patients, 45 cases (46.8%) and 51 controls (53.1%). The MTWA test was non-negative in 36/45 cases (80%) and 15/51 controls (29.4%) [OR = 9.60 (95%CI: 3.41 - 27.93)]. After adjustment for known confounding factors in a logistic regression model, the non-negative result continued to be associated with malignant ventricular arrhythmias [OR = 5.17 (95%CI: 1.05 - 25.51)].ConclusionPatients with CCC and history of malignant ventricular arrhythmias more often have a non-negative MTWA test as compared to patients with no history of arrhythmia.

Non-sustained microvolt level T-wave alternans in congenital long QT syndrome types 1 and 2

BackgroundPatients with long QT syndrome (LQTS) are predisposed to polymorphic ventricular tachycardia (VT) during adrenergic stimulation. Microvolt T-wave alternans (MTWA) is linked to vulnerability to VT in structural heart disease. The prevalence of non-sustained MTWA (NS-MTWA) in LQTS is unknown. Methods31 LQT1, 42 LQT2, and 80 controls underwent MTWA testing during exercise. MTWA tests were classified per standardized criteria, and re-analyzed according to the modified criteria to account for NS-MTWA. ResultsLQT1 and LQT2 patients had a significantly higher frequency of late NS-MTWA (26% and 12%) compared to controls (0%). There was no significant difference between the groups with respect to sustained and early NS-MTWA. Late NS-MTWA was significantly associated with QTc. ConclusionLQT1 and LQT2 patients had a higher prevalence of late NS-MTWA during exercise than matched controls. NS-MTWA likely reflects transient adrenergically mediated dispersion of repolarization, and could be a marker of arrhythmic risk in LQTS.

Usefulness of microvolt T-wave alternans for predicting outcome in patients with Chagas disease with implantable cardioverter defibrillators

BackgroundChagas disease (ChD) may lead to life-threatening heart disease, including malignant ventricular arrhythmias. The use of implantable cardioverter defibrillators (ICDs) has become the main therapeutic strategy for secondary prevention of SCD in Chagas disease (ChD). Microvolt T-wave alternans (MTWA) is a direct measure of ventricular repolarization instability and has emerged as a potentially useful way of determining arrhythmia vulnerability. However, this methodology has not been evaluated in patients with ChD. ObjectiveTo evaluate the predictive value of MTWA testing for appropriate therapy or death in ChD patients with ICDs. MethodsThis prospective study included consecutive patients who received ICD implantations in a Brazilian tertiary referral center. ResultsSeventy-two patients were followed for a median time of 422 (range 294–642) days. Thirty-three patients had ChD. The MTWA was non-negative (positive or indeterminate) in 27 (81.8%) of ChD patients. The combined primary outcome (appropriate ICD therapy or death) occurred in 29 patients (40.3%); 17 out 33 ChD patients presented the primary outcome. There was a statistically significant difference in event-free survival between ChD patients with negative and non-negative MTWA results (p=0.02). Non-negative MTWA tests nearly triple the risk of appropriate ICD therapy or death (HR=2.7, 95% CI: 1.7–4.4, p=0.01) in patients with ChD and was the only variable associated with outcomes. The sensitivity and the negative predictive value was 100% in ChD patients. ConclusionsMTWA may be useful in recognizing high-risk ICD patients who may require adjunctive therapies with antiarrhythmic drugs or catheter ablation.

Prediction of Appropriate Shocks Using 24-Hour Holter Variables and T-Wave Alternans After First Implantable Cardioverter-Defibrillator Implantation in Patients With Ischemic or Nonischemic Cardiomyopathy

In patients treated with implantable cardioverter defibrillator (ICD), prediction of both overall survival and occurrence of shocks is important if improved patient selection is desired. We prospectively studied the predictive value of biomarkers and indexes of cardiac and renal function and spectral microvolt T-wave alternans testing and 24-hour Holter variables in a population who underwent first ICD implantation. Consecutive patients in sinus rhythm with ischemic or dilated cardiomyopathy scheduled for primary or secondary prophylactic ICD implantation were enrolled. Exercise microvolt T-wave alternans and 24-hour Holter for number of ventricular premature contractions (VPCs), deceleration capacity, heart rate variability, and heart rate turbulence were done. Death of any cause and first appropriate ICD shock were defined as end points. Over 33 ± 15months of follow-up, 36 of 253 patients (14%) received appropriate shocks and 39 of 253 patients (15%) died. Only 3 of 253 patients (1%) died after receiving at least 1 appropriate shock. In univariate analyses, New York Heart Association class, ejection fraction, N-terminal pro brain-type natriuretic peptide (NT-proBNP), renal function, ICD indication, deceleration capacity, heart rate variability, and heart rate turbulence were predictive of all-cause mortality and VPC number and deceleration capacity predicted first appropriate shock. NT-proBNP (≥1,600 pg/ml) was identified as the only independent predictor of all-cause mortality (hazard ratio 3.0, confidence interval 1.3 to 7.3, p= 0.014). In contrast, VPC number predicted appropriate shocks (hazard ratio 2.3, confidence interval 1.0 to 5.5, p= 0.047) as the only independent risk marker. In conclusion, NT-proBNP is a strong independent predictor of mortality in a typical prospective cohort of newly implanted patients with ICD, among many electrocardiographic and clinical variables studied. Number of VPCs was identified as a predictor of appropriate shocks (clinicaltrials.gov: NCT02010515).

Rate-dependent force, intracellular calcium, and action potential voltage alternans are modulated by sarcomere length and heart failure induced-remodeling of thin filament regulation in human heart failure: A myocyte modeling study

Microvolt T-wave alternans (MTWA) testing identifies heart failure patients at risk for lethal ventricular arrhythmias at near-resting heart rates (<110 beats per minute). Since pressure alternans occurs simultaneously with MTWA and has a higher signal to noise ratio, it may be a better predictor of arrhythmia, although the mechanism remains unknown. Therefore, we investigated the relationship between force alternans (FORCE-ALT), the cellular manifestation of pressure alternans, and action potential voltage alternans (APV-ALT), the cellular driver of MTWA. Our goal was to uncover the mechanisms linking APV-ALT and FORCE-ALT in failing human myocytes and to investigate how the link between those alternans was affected by pacing rate and by physiological conditions such as sarcomere length and heart failure induced-remodeling of mechanical parameters. To achieve this, a mechanically-based, strongly coupled human electromechanical myocyte model was constructed. Reducing the sarcoplasmic reticulum calcium uptake current (Iup) to 27% was incorporated to simulate abnormal calcium handling in human heart failure. Mechanical remodeling was incorporated to simulate altered thin filament activation and crossbridge (XB) cycling rates. A dynamical pacing protocol was used to investigate the development of intracellular calcium concentration ([Ca]i), voltage, and active force alternans at different pacing rates. FORCE-ALT only occurred in simulations incorporating reduced Iup, demonstrating that alternans in the intracellular calcium concentration (CA-ALT) induced FORCE-ALT. The magnitude of FORCE-ALT was found to be largest at clinically relevant pacing rates (<110 bpm), where APV-ALT was smallest. We found that the magnitudes of FORCE-ALT, CA-ALT and APV-ALT were altered by heart failure induced-remodeling of mechanical parameters and sarcomere length due to the presence of myofilament feedback. These findings provide important insight into the relationship between heart-failure-induced electrical and mechanical alternans and how they are altered by physiological conditions at near-resting heart rates.

Electromuscular incapacitating devices discharge and risk of severe bradycardia.

Electromuscular incapacitating devices (EMDs) are high-voltage, low-current stimulators causing involuntary muscle contractions and sensory response. Existing evidence about cardiac effects of EMD remains inconclusive. The aim of our study was to analyze electrocardiographic, echocardiographic, and microvolt T-wave alternans (MTWA) changes induced by EMD discharge.We examined 26 volunteers (22 men; median age 30 years) who underwent single standard 5-second duration exposure to TASER X26 under continuous echocardiographic and electrocardiographic monitoring. Microvolt T-wave alternans testing was performed at baseline (MTWA-1), as well as immediately and 60 minutes after EMD exposure (MTWA-2 and MTWA-3, respectively).Mean heart rate (HR) increased significantly from 88 ± 17 beats per minute before to 129 ± 17 beats per minute after exposure (P < 0.001). However, in 2 individuals, an abrupt decrease in HR was observed. In one of them, interval between two consecutive beats increased up to 1.7 seconds during the discharge. New onset of supraventricular premature beats was observed after discharge in 1 patient. Results of MTWA-1, MTWA-2, and MTWA-3 tests were positive in one of the subjects, each time in a different case.Standard EMD exposure can be associated with a nonuniform reaction of HR and followed by heart rhythm disturbances. New MTWA positivity can reflect either the effect of EMD exposure or a potential false positivity of MTWA assessments.

Large Amplitude Rate-Dependent Mechanical Alternans may Precede Arrhythmogenesis in Human Heart Failure and are Linked to Electrical Alternans via Abnormal Calcium Handling

Microvolt T-wave alternans (MTWA) testing identifies patients at risk for lethal ventricular arrhythmias. However, stratification of low and high risk patients with MTWA is challenging due in part to poor signal-to-noise ratio (SNR) of MTWA measurements. Since microscopic systolic pressure alternans (MSPA) has a higher SNR than MTWA, and is also associated with abnormal calcium handling, we hypothesized that rate-dependent MSPA also precedes arrhythmia and may be an alternative approach for arrhythmia risk stratification in heart failure patients. To test this hypothesis, we investigated mechanical alternans, a surrogate for MSPA, and its proposed link to arrhythmogenesis via abnormal calcium handling. Electromechanical models of single human myocytes were constructed. Key features of remodeling were incorporated to simulate abnormal calcium handling in human heart failure. A dynamical pacing protocol was used to investigate intracellular calcium concentration ([Ca]i), voltage, and force for different pacing rates. In normal myocytes, [Ca]i, voltage, and force alternans were not found for pacing rates <200 bpm. In the presence of deranged calcium handling common in heart failure (sarcoplasmic calcium reuptake reduced below 74%), [Ca]i, AP phase II voltage, and force alternans developed at moderate pacing rates <120 bpm and increased in magnitude with increased pacing rate. For all pacing rates, the ratio of force alternans to peak force was at least tenfold larger than the ratio of AP phase II voltage alternans to maximum AP phase II voltage. In conclusion, electrical and mechanical alternans are both rate-dependent and linked via abnormal calcium handling, but mechanical alternans has the greatest amplitude across all pacing rates. Thus, mechanical alternans, due to their greater SNR, may be better predictors for arrhythmogenic propensity in heart failure patients than electrical alternans.

Application of microvolt T-wave alternans testing in scheduling implantable cardioverter-defibrillator placement for the primary prevention of sudden cardiac death in patients with left ventricular dysfunction.

Patients with left ventricular ejection fraction (LVEF) ≤ 35% are eligible for implantable cardioverter-defibrillator (ICD) placement for the primary prevention of sudden cardiac death (SCD). This recommendation results in continuously growing waiting lists of patients who have been qualified for and are awaiting the procedure. Whiled reduced LVEF is a feature shared by all the patients in this group, the risk of malignant ventricular arrhythmias varies widely. It therefore seems important from the clinical point of view to improve the waiting lists by identifying patients at the lowest risk of SCD, who can safely wait for the procedure, while higher-risk patients undergo the procedure before them. To verify the utility of microvolt T-wave alternans (MTWA) testing, which is characterised by high negative predictive value (NPV), in scheduling ICD implantation in these patients. The study included 152 patients with LVEF ≤ 35%, qualified for ICD implantation for the primary prevention of SCD, and managed in accordance with the current recommendations. Patients with a history of malignant ventricular arrhythmias were excluded. Each patient underwent MTWA testing during chronic treatment (including beta-blockers) and was followed-up. During 14 ± 8 months of follow-up, the primary outcome, which included SCD, non-fatal sustained ventricular arrhythmia, or appropriate high-voltage ICD discharge, was observed in 16 patients. The one-year event rate was 13.1% (5.8-19.8%) in non-negative MTWA patients and 0% in those who had negative MTWA result (p = 0.027). The NPV of the MTWA test was 100% (95% CI 92.73- 00%). In the group of patients with left ventricular systolic dysfunction, excluding patients with a history of malignant ventricular arrhythmia, the NPV of MTWA was 100% over 12 months of observation. MTWA may therefore be considered useful in determining the order of ICD implantation procedures in this group of patients by identifying patients at a relatively low risk of malignant ventricular arrhythmias, who can be relatively safely rescheduled for ICD implantation at a later time. Future studies should concentrate on this issue.

Prognostic value of microvolt T-wave alternans in a real-world ICD population. Twente ICD Cohort Studie (TICS).

IntroductionSurvival benefit from ICD implantation is relatively low in primary prevention patients. Better patient selection is important to maintain maximum survival benefit while reducing the number of unnecessary implants. Microvolt T-wave alternans (MTWA) is a promising risk marker. In this study, we aimed to evaluate the predictive value of MTWA in ICD patients.Methods and resultsThis study was a substudy of the Twente ICD Cohort Study (TICS). Patients with ischaemic or non-ischaemic left ventricular dysfunction who received an ICD following current ESC guidelines were eligible for inclusion. Exercise-MTWA was performed and classified as non-negative or negative. The primary endpoint was the composite of mortality and appropriate shock therapy. Analysis was performed in 134 patients (81 % male, mean age 62 years, mean ejection fraction 26.5 %). MTWA was non-negative in 64 %. There was no relation between non-negative MTWA testing and mortality and/or appropriate shock therapy (all p-values >0.15). Due to clinical conditions, 24 % were ineligible for testing. These patients experienced the highest risk for mortality (p < 0.01).ConclusionNon-negative MTWA testing did not predict mortality and/or appropriate shock therapy. Furthermore, MTWA testing is not feasible in a large percentage of patients. These ineligible patients experience the highest risk for mortality.

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.

Microvolt T-wave alternans testing in patients recently hospitalized with decompensated heart failure

Microvolt T-wave alternans testing in patients recently hospitalized with decompensated heart failure

A translational approach to probe the proarrhythmic potential of cardiac alternans: a reversible overture to arrhythmogenesis?

Electrocardiographic alternans, a phenomenon of beat-to-beat alternation in cardiac electrical waveforms, has been implicated in the pathogenesis of ventricular arrhythmias and sudden cardiac death (SCD). In the clinical setting, a positive microvolt T-wave alternans test has been associated with a heightened risk of arrhythmic mortality and SCD during medium- and long-term follow-up. However, rather than merely being associated with an increased risk for SCD, several lines of preclinical and clinical evidence suggest that cardiac alternans may play a causative role in generating the acute electrophysiological substrate necessary for the onset of ventricular arrhythmias. Deficiencies in Ca(2+) transport processes have been implicated in the genesis of alternans at the subcellular and cellular level and are hypothesized to contribute to the conditions necessary for dispersion of refractoriness, wave break, reentry, and onset of arrhythmia. As such, detecting acute surges in alternans may provide a mechanism for predicting the impending onset of arrhythmia and opens the door to delivering upstream antiarrhythmic therapies. In this review, we discuss the preclinical and clinical evidence to support a causative association between alternans and acute arrhythmogenesis and outline the potential clinical implications of such an association.

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.

Mechanism of sudden cardiac death in obstructive sleep apnea, revisited

Obstructive sleep apnea (OSA) raises the risk of sudden cardiac death (SCD) by 300–400% depending on the severity of OSA. However published reports raised the association between OSA and SCD but not the mechanism of SCD. It is known that OSA exerts profound oxidative stress in the cardiovascular system. Repetitive nocturnal hypoxemia and arousals lead to ischemia reperfusion, cellular degeneration, and apoptosis, cardiac remodeling such as diastolic and systolic dysfunctions; which provide fertile environment for reentrant arrhythmias. Increase temporal dispersion in myocardial depolarization has been shown to enhance the genesis of malignant arrhythmias that in turn raise sudden death risk. We postulated that OSA leads to higher incidence of SCD due to reentrant arrhythmias initiated by ventricular extrasystoles that excite myocardial fibers at the height of its vulnerable period, reentrant beats trigger runs of ventricular tachycardia and ventricular fibrillation. We deployed microvolt T-wave alternans (MTWA) as a tool to measure myocardial vulnerability. We attempted to determine if OSA leads to higher incidence of positive microvolt T-wave alternan (MTWA+); thus higher risk for arrhythmic death; and correlated MTWA result with severity of OSA as measured by apnea hypopnea index (AHI). 201 (M/F 1.1/1) patients with OSA of varying severity underwent MTWA in a random manner. We segmented the patients into MTWA positive (MTWA+), MTWA Indeterminate (MTWAI), MTWA negative (MTWA-). We then analyzed the MTWA result in relation to AHI. It has been shown that MTWA+ and MTWAI patients have higher risk of SCD usually from ischemia and cardiomyopathy. There was a higher incidence of MTWA+ ( p -value < 0.004) and MTWAI ( p -value < 0.001) in severe OSA “AHI 30–50” and unusually severe OSA “AHI > 50” MTWA+ ( p -value < 0.003), MTWAI ( p -value < 0.001 respectively). These two subgroups of OSA could be at higher risk for arrhythmic deaths since MTWA+ and MTWAI patients have higher mortality rate from malignant arrhythmias than MTWA−. sp020The severity of OSA is directly proportional to the incidence of MTWA positive (MTWA+) and MTWA indeterminate test (MTWAI). Severe and unusually severe OSA patients could be at higher risk of arrhythmic death than milder OSA as measured by MTWA. Cambridge Heart sold the equipment and supplies to Chanwell Clinic in the performance of MTWA test.