Risk stratification for Sudden Cardiac Death (SCD)

Definition of TWA

Definition: Repeating ABAB pattern in amplitude and shape of ST segment and T wave. The TWA level shown in the QRS-aligned template (as left) is 124 microvolts. The recording is from a FINCAVAS patient who died of cardiovascular causes at ~ 1 year. From: Minkkinen et al JCE 2009;20:408

About T-Wave Alternans

T-Wave Alternans (TWA) is an electrophysiological phenomenon that is evident in the ECG as an alternating pattern of ST/T-Wave morphologies on successive beats. Although the alternation can be present in both the ST segment and T-Wave, the entire pattern is simply referred to as TWA. The Modified Moving Average T-Wave Alternan (TWA) algorithm measures and quantifies the alternations on beat-to-beat patterns, precisely detecting fluctuations in the ECG waveform. TWA enables physicians to identify an oŽen-missed pattern variation that may indicate a high level of SCD risk and helps support earlier treatment decisions. Performing a TWA test is useful for patients who have had an MI, family history of MI and/or SCD, on beta-blockers, using an antiarrhythmic drug, or will be using an antiarrhythmic drug. Not recommended for patients with atrial fibrillation. Source: T-Wave Alternans Physician’s Guide, 2020044-067 Revision C, © 2008–2009 General Electric Company.

TWA preceding VT During exercise test

Computer-processed data: Superimposed A & B beats

Raw data confirms TWA

Later, during recovery: Episode of VT

Acquiring and processing the ECG signal

Test protocol and setup

  • T-Wave Alternans can be collected during a standard Holter or ECG exercise stress test.
  • Use standard electrodes. See Skin Preparation and Electrode Placement, right. 
  • Maintain usual medications. 
  • No minimum heart rate is required. 
  • Heart rate limit = 125 beats/min. 
  • Update factor = 1/8. 
  • Noise limit = 20 μV

Skin preparation and electrode placement

TWA is a regionally specific phenomenon. Use precordial leads whenever possible. Use of Frank X, Y, or Z leads is not recommended for TWA monitoring. 

  1. Ensure each electrode site is dry, clean, and free of excess hair. 
  2. Degrease each electrode site with a skin preparation cream. 
  3. Using a synthetic abrasive pad, clear away a layer of skin. 
  4. Apply standard electrodes on precordium and limbs 
  • Precordial leads provide the most useful information for TWA testing. 
  • Ideally, right and left parasternal electrodes should not be placed on pectoral muscles. 
  • Allow slack in wires for movement.

Modified moving average method (MMA)

  • Analyzes TWA in time domain 
  • Continuously streams A and B forms 
  • Identifies peak alternation between consecutive beats in JT interval per 15 seconds 
  • Does not require fixed heart rate 
  • Uses standard electrodes 
  • Patients maintain medications 
  • 1-Microvolt resolution 
  • Full disclosure ECG available 
  • Provides TWA template for computer-aided waveform inspection

Reviewing TWA measurements and templates

Templates and display information

High resolution ECGs are superimposed for visual inspection: 

  • Rule out waveforms not TWA 
  • P-wave and QRS should be aligned 
  • Confirm TWA visually down to 20 μV

Visual confirmation - ambulatory ECGs

A trend of TWA values, stored every 10 seconds. Go to any point and obtain associated raw data and TWA template.

Recommended Screen Layout Rhythm Strip, Time Synchronized TWA Trend

Visual confirmation - exercise ECGs

Trends - Positive TWA at 8 minutes. Dashed trends of TWA values have noise values > 20µV.

Templates - QRS complex is aligned. Noise value < 20µV

Full disclosure of Raw Data - TWA pattern visible in full disclosure data at point of positive TWA measurement.

Time synchronized trends + Templates + Row data = Quick visual confirmation

Test interpretation

TWA test interpretation

  • Cutpoint for abnormal results: ≥ 47μV 
    • Severely abnormal: ≥ 60 μV 
    • Larger TWA = greater risk 
  • Hazard ratios for positive TWA test:
  • Indeterminate tests (2-5%) may result from ventricular ectopy, technically poor readings. 
  • Not recommended: Assessment during AF, high-grade ectopy, supraventricular arrhythmias, or conduction block. 
  • CAVEAT: Results of TWA tests should be used as an adjunct to clinical history, symptoms, and the results of other noninvasive and invasive tests.

Microvolt TWA Consensus Guideline, JACC 2011; 44:1309–1324

Higher TWA = higher risk of SCD

TWA ≥ 47 µV = risk of SCD. TWA ≥ 60 µV = severe risk of SCD. Microvolt TWA Consensus Guideline, JACC 2011; 44:1309–1324

Each 20-uV increase in TWA indicates +58% SCD risk. Leino et al Heart Rhythm 2011; 8(3): p. 385-90

Further reading

Duca ST, Roca M, Costache AD, et al. T-Wave analysis on the 24 h Holter ECG monitoring as a predictive assessment of major adverse cardiovascular events in patients with myocardial infarction: A literature review and future perspectives. Life (Basel) 2023; 13(5):1155. https://www.mdpi.com/2075-1729/13/5/1155&nbsp;

Aro AL, Kenttä TV, Huikuri HV. Microvolt T-wave alternans: Where are we now? Arrhythmia & Electrophysiology Review 2016; 5(1):37-40. https://www.aerjournal.com/articles/microvolt-t-wave-alternans-where-ar…;

Lewek J, Ptaszynski P, Klingenheben T, Cygankiewicz I. The clinical value of T-wave alternans derived from Holter monitoring. Europace 2017; 19(4):529-534. https://academic.oup.com/europace/article/19/4/529/2952436&nbsp;

You T, Luo C, Zhang K, Zhang H. Electrophysiological mechanisms underlying T-wave alternans and their role in arrhythmogenesis. Frontiers in Physiology 2021; 12:614946. https://www.frontiersin.org/articles/10.3389/fphys.2021.614946/full.&nb…;

Verrier RL, Klingenheben T, Malik M, El-Sherif N, Exner D, Hohnloser S, Ikeda T, Martinez JP, Narayan S, Nieminen T, Rosenbaum DS. Microvolt T-wave alternans: Physiologic basis, methods of measurement, and clinical utility. Consensus guideline by the international Society for Holter and Noninvasive Electrocardiology. J Am Coll Cardiol 2011; 44:1309-1324.

 

Abbreviations: CV = Cardiovascular; SCD = Sudden Cardiac Death; NPV = Negative Predictive Value

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