Micro Volt T Wave Alternans (MTWA)

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Micro Volt T Wave Alternans (MTWA)

• ( Analytic Spectral Method)

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Microvolt T-Wave Alternans

• What is TWA?
• Published Clinical Data and ongoing trials
• Suggested Clinical use protocols
• How is an alternans test performed?
• How is the test interpreted?

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T-Wave Alternans
Visible
Predicts immediate (VT/VF).
Microvolt Level
Measured with proprietary spectral method at
heart rates. Predicts 2 year VT/VF.
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T-Wave Alternans
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(No Transcript)
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Spectral Method Detection of Microvolt TWA
Beat Series
Smith, Clancy, Valeri, Ruskin, and Cohen.
Circulation 198877110-121
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High Risk Groups for SCD
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Sudden Death Risk Factors
Trigger
LVEF/ MI
MTWA / Electr. Instability
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Do we need a better risk stratification method?
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Microvolt T-Wave Alternans

• Whats TWA
• Published Clinical Data (all clinical data
  published are based on Analytic Spectral Method)
• Ongoing trials
• Suggested Clinical Use Protocols
• How is an alternans test performed?
• How is the test interpreted?

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MGH / MIT Study
EP Study
Rosenbaum, Jackson, Smith, Garan, Ruskin and
Cohen N Engl J Med 1994330235-241
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Multi-Center Regulatory Study Prediction of
VT/VF, ICD Firing and Total Mortality
Gold MR, et al. A Comparison of TWA, SAECG, EP
for Arrhythmia Risk Stratif. JACC Vol 36,7,2000.
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Syncope Substudy
Bloomfield DM, Gold MR, Anderson KP, Wilber DJ,
El-Sherif N, Estes NAM, Groh WJ, Kaufman ES,
Greenberg ML, Rosenbaum DS, Dabbous O, Cohen RJ.
AHA, 1999.
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Frankfurt CHF Study Preliminary Results in 81
patients
Plt0.001
Klingenheben , Hohnloser SH. The Lancet Dec. 2000.
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Non-Ischemic DCM StudyJACC 2003 Results in 137
patients
Kllingenheben T, Bloomfield, D, Cohen, R,
Hohnloser, S JACC Vol 41 N.12 2003
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Preditive value of MTWA Onset Heart Rate

• Kitamura JACC Jan 2002 104 DCM patients pts

Tanno, Circulation, 2004 109 1854-1858 on 248
ischemic and non ischemic patients has found
similar results
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Ikeda Post-MI Study
Ikeda, T,The American J. Cardiol Vol 89, Jan
1,2002
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Post MI MTWA (Large Multicenter Study)
Design

• Prospective study, 834 consecutive patients,
  infarct survivors, 7 Japanese centers.
• Prognostic Indices TWA, LP, EF, NSVT
• Endpoint SCD or resuscitated VF
• Follow-up 25 13 months

Conclusions These findings from a large
prospective study demonstrate that TWA is a
strong risk stratifier for sudden cardiac death
after myocardial infarction.
Ikeda, T,The American J. Cardiol Vol 89, Jan
1,2002
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850 pz. Post MI - 25 SCD VF Events.( AJC Jan
2002)
Sens. NPV RH
MTWA 22/24 (92) 435/437(99) 11
LVEF 14/25 (56) 672/683(98) 6
NSVT 12/25 (48) 611/624(98) 4
LP 11/22 (50) 544/555(98) 5
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MTWA study in Athletes (F. Furlanello, G.
Galanti, A. Michelucci, D. Marangoni, R. Cappato)

• 100 athletes ( no Organic Heart Disease)
• 48 healthy 45 MTWA- 3 indeterm.
• 52 arrhythmic athletes
• 42 MTWA- (1 amiodaron) 3 indeterm. 41 EP- (1
  amio)
• 7 MTWA
• 5 EP 2 ICD 1Myocarditis 1 Amio 1 RFCA
• 1 EP- (but with NSVT)
• 1 no EP
• 25 months follow up no events in TWA- 1 ICD
  multiple discharges in TWA
• A.N.E. 2004 9(3)1-6

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MTWA with Exercise in Pediatrics and Congenital
Heart Disease Limitations and Predictive Value

• TWA is associated with pediatric and CHD
  diagnoses at high risk of serious events and may
  contribute, with other diagnostic tools, to
  management choices.(Pacing Clin Electrophysiol.
   200629(7)733-741)

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Antiarrhythmic Drug Study

• 49 patients w/ Cardiomiopathy and VT/VF
• Class I and III antiarrhythmic drug (Amiodarone
  57)
• Study endpoint Recurrence of VT/VF in 13 months
• Result PPV 67 NPV 71
• Conclusion TWA significantly predicts
  reoccurrence of VT even on antiarrhythmic drug.
  TWA may be also a useful marker for evaluating
  the efficacy of antiarrhythmic drug

Koiki Sakabe A.N.E. 2001 6(3) 203-208
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Beta Blocker Study

• 65 patients with prior VT
• T-wave alternans measured atrial pacing at
  baseline and during beta blockade with metoprolol
  and d,I-sotalol
• Both SOT and MET resulted in a reduced TWA
  Amplitude but not in a change of TWA Onset HR.
• Conclusion There are comparable effects of SOT
  and MET. TWA can be assessed during ongoing
  therapy if target Heart Rate of 110bpm can be
  reached.

Klikenhaben J Am Coll Card 2001382013-9.
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Event Rates of EPS and TWA

• Singly In Combination
• EPS 25 EPS, TWA 39
• TWA 25 EPS-, TWA 15
• EPS- 5 EPS, TWA- 12
• TWA- 1.5 EPS-, TWA- 0

Rashba, Gold MR, et al. . Enhanced vulnerability
using TWA and EP PACE 2002 25(4,Part Ii)
523-750
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MADIT II

• (HF post MI with EF lt 30)
•         This study will increase the number of
  ICD implanted from its current level of 60.000 by
  two fold to 120,000 (USA)- and 4 times in Europe.
  
• SCD-Heft (EF lt35) will multiply again the number
  of implants ( Class II on Guidelines)

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Ikeda AHA 2002 prospective study on MADIT II
patients

• VT and SD primary end points
• 1/25 negative TWA patient had Sustained VT but
  no SD or VF

Data published on 129 pts with Hohnloser on The
Lancet 2003 362125-26
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TWA in MADIT II Population Multi-Center CHF
Study2 death rate (twa-) comparared to 10 in
ICD arm of Madit II
Bloomfield, Daniel et alt Circulation 2004
1101885-1889
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Bloomfield MADIT II Patients
Bloomfield, Circulation, 2004 110 1885-1889
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Baravelli and Salerno Predictive Significance
for SCD of Microvolt level T wave Alternans in
NYHA class II CHF patients A Prospective study
Baravelli et al, International Journal of
Cardiology, March 2005
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ICD placed / life saved

• MADIT II
• MTWA negative
• MTWA positive
• MUSTT

• 18 (11 at 3 yrs )
• -30
• 5
• 4

Data extracted from D. Bloomfield Circulation 2004
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Jacc 2006, Vol 47 N. 2 Daniel Bloomfield

• 549 patients LVEF lt40 (MADIT II and SCD-Heft
  included)
• 2 years follow up
• End points death and Sustained VT/VF than LVEF
• TWA was significantly better univariate and
  multivariate predictor of death and Sustained
  VT/VF

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MTWA is a Powerful Arrhythmic Risk Stratifier
Antonis A. Armoundas, Stefan Hohnloser, Takanori
Ikeda, Richard J. Cohen, Nature Clinical
Practice, October 2005
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All Cause Mortality is Lower in MTWA Negative
Patients Who Did Not Receive ICDs than in
Comparable Patients in the MADIT-II and SCD-HeFT
Trials who Did Receive ICDs
Antonis A. Armoundas, Stefan Hohnloser, Takanori
Ikeda, Richard J. Cohen, Nature Clinical
Practice, October 2005
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Annualized mortality ()
1 Year Total Mortality
TRIAL
Chow6 -
MADIT II1
SCD-Heft2
TWA-CHF3
TWA-CHF4
Hohnloser5
OHD
NICM EF lt 0.40
ICM EF lt 0.30
ICM EF lt 0.35
ICM NICM EF lt 0.35
ICM EF lt 0.30
ICM EF lt 0.40
FU(mo)
20
60
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24
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18 - 40
ANNUALIZED MORTALITY ()

1. Costantini et al. Circulation 2004110667
   (Supp)
2. Hohnloser et al Lancet 2003362125
3. Chow et al. JACC 2006471820

1. Moss et al. NEJM 2002346877
2. Bardy et al. NEJM 2005352225
3. Bloomfield et al Circulation. 20041101885

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Meta- Analysis on 2608 patients in published
trials.( JACC 20054675-82 )

• Negative Predictive Value 97.2
• Positive Predictive Value 19.2

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ACC 2006 Investigator award

• Cost-effectiveness of ICD implantation including
  the initial cost of ICD implant, cost of MTWA
  testing, complications, ICD replacements, death
  rates, etc.
• The results of the simulations revealed an
  Incremental Cost Effectiveness Ratio of 88,700
  per Quality Adjusted Life Year in the ICDs FOR
  ALL strategy as compared to the use of MTWA risk
  stratification. (JACC June 7 2006 ) and
  confirmed by Dr MOSS study (JACC 2006
  472310-2318)

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Costs of Healthcare will go outside national
budgets so that MEDICARE has DETERMINED that
There is sufficient evidence to conclude that
microvolt TWA testing using only the spectral
analytic method can improve net health outcomes
and is reasonable and necessary for patients who
are candidates for ICD placement.. MTWA can
identify which heart patients are at NEGLIGIBLE
risk of sudden death, and who may therefore be
able to avoid ICD implantation and its attendant
RISK. ..March 21, 2006
CMS proposes Medicare coverage for T-wave
alternans ICD risk-stratification test
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ICD risks

• Prophylactic Defibrillator Therapy Is Associated
  With Increased Mortality in Microvolt T-Wave
  Alternans Negative Patients With Ischemic
  Cardiomyopathy (ACC 2005 abstract). Data
  reported also in Prognostic Utility of Microvolt
  T-Wave Alternans in Risk Stratification of
  Patients With Ischemic Cardiomyopathy JACC Vol
  47, No 9 2006, May 2nd
• Frequency and causes of implantable
  cardioverter-defibrillator therapies is device
  therapy proarrhythmic?Am J Cardiol 2006 April 15
  .

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ACC/AHA/ESC 2006 NEW Guidelines for VA SCD
patients (August 2006)

• It is reasonable to use TWA for improving the
  diagnosis and risk stratification of patients
  with Ventricular Arrhythmias (VA) or who are at
  risk for developing life threatening VA. Class
  IIa (Level of Evidence A)
• ICD trials especially MADIT II have highlighted
  the need to develop novel tools in order to
  identify patients at highest risk of VA and SCD.

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Mtwa icd strategy (1)

• Clinical
• - class 2 applications (scd-heft)
• - EF borderline
• - help to increase the primary prevention
  application penetration ( only 10 ) for
  patients or doctors reluctant to ICD implantation
  (for possible ICD / quality of life
  complications)
• - EP test cases of difficult interpretation

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Mtwa icd strategy (2)

• Economic Efficiency
• - not acceptable costs per quality adjusted life
  year gain (50.000 ) 
• - budget limitation not enough ICDs for all
  primary (Class I) prevention patients A
  selection has to be made also according to the
  new 2006 guidelines suggestions.

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New trials with device implantation to validate
the positive predictive value
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ABCD TrialProtocol MUSTT population400
patients, 42 Centers
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MASTER Trial on Madit II Patients

• Largest trial 1800 patients
• Post MI, EFlt40 Madit II MTWA
• ICD implanted in all MADIT II patients
• 60 Centers US Start September 2003

• CARISMA Northen Europe study
• Post MI, EF lt40, Loop recorder implanted
• 10 Centers, 400 Patients end enrollement Dec.
  2004

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Comparison to Other Risk MarkersPrediction of
Arrhythmia-Free Survival
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Microvolt T-Wave Alternans

• Whats TWA
• Published Clinical Data and ongoing trials
• Suggested Clinical Use Protocols
• How is an alternans test performed?
• How is the test interpreted?

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Diagnosis and Treatment Model
High Risk Patients
Stress test with the CH 2000
Ischemia
T-wave Alternans
Electrophysiology Study
Coronary Angiography
ICD, ablation, drugs
CABG or Angioplasty
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Suggested protocols
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(No Transcript)
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Microvolt T-Wave Alternans

• Whats TWA
• Published Clinical Data and ongoing trials
• Suggested Clinical Use Protocols
• How is an alternans test performed?
• How is the test interpreted?

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Heart Rate Dependence of TWA
Rosenbaum, et al
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Measurement of TWA with CH-2000

• Full featured stress system
• 3 Pretest Lead checks
• 14 leads standard stress test option
• Proprietary Diagnostic Screen Grid

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New HearTwave II

• Designed for best MTWA testing.
• Windows XP operating system
• Includes ECG monitoring
• Upgradeable to full Stress test

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Methods to increase Heart Rate

• Treadmill or Ergometer
• Pharmacologic (Dobutamine)
• Pacing
• Atrial
• AV Sequetial with AV delay of 180 msec
• AV Simultaneous.

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MTWA in Atrial Fibrillation patients

• Microvolt T-wave alternans during exercise and
  pacing in patients with acute myocardial
  infarction. PACE 200528Suppl 1S193-7.
• Simultaneous VA pacing can be used to assess
  TWA also in patients with atrial fibrillation and
  impaired AV nodal conduction. This approach also
  eliminates retrograde atrial activation and/or
  random sinus activity at descending portion of
  the T wave, which may obscure the TWA analysis
  during ventricular pacing. The data obtained with
  VA pacing were similar to those measured during
  the bicycle exercise and A pacing

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High-Resolution ElectrodesMake noninvasive test
feasible
ECG (Center)
Adaptive cancellation reduces noise due to
patient movement
ECG (Segment)
Impedance
Respiration
Noise Reduction
Noise Reduced
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Microvolt T-Wave Alternans

• Whats new?
• How are EPs using the test clinically?
• How is an alternans test performed?
• How is the test interpreted?

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Positive TWA Test (automatic interpretation)

• Sustained Alternans
• Valt ? 1.9 µV
• Alternans ratio ? 3
• Positive HR threshold
• Onset HR lt 110 bpm

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Negative TWA Test (automatic interpretation)

• No Sustained Alternans
• HR of gt 105 achieved

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www.alternans.org

• All updated information on T Wave Alternans