T-wave alternans could surpass LVEF as risk-stratifier for ICD implantation

May 11, 2005

Steve Stiles

 

New Orleans, LA - T-wave alternans-(TWA) testing has a very low false-negative rate when stratifying cardiomyopathy patients for risk of death or sustained ventricular arrhythmias, adds to risk assessments with LVEF alone, and isn't muddled by prolonged QRS intervals, according to post hoc analyses of a prospective, observational trial.[1,2] The findings add to mounting evidence that the noninvasive TWA test, which monitors shape variations in the electrocardiographic T-wave at exercise, can sharpen the screening of candidates for a primary-prevention implantable cardioverter-defibrillator (ICD).

Dr J Thomas Bigger

In the T-wave Alternans in Heart Failure (TWA in HF) trial, the TWA test "was at least twice as strong in predictive value as ejection fraction, which is an incredibly good risk stratifier," Dr J Thomas Bigger (Columbia University, New York, NY), told heartwire. "Furthermore, if you use both of them together, you can get a group with very high risk and a group with very low risk approaching zero."

After presenting the findings last week at the Heart Rhythm Society 2005 Scientific Sessions, Bigger's Columbia colleague Dr Sarah B Levin sliced the trial's data another way and found equal predictive values for TWA in patients with QRS durations <120 ms compared with those with longer QRS intervals.

The Centers for Medicare & Medicaid Services (CMS) had commented that TWA would be worth exploring as a potential risk indicator for screening primary-prevention ICD candidates when it proposed reimbursement criteria for such devices in September 2004.[3,4] The official decision in January 2005 was more expansive than the proposal, allowing reimbursement for ICD candidates in NYHA class 2-3 with an LVEF <35% and class-4 patients if they are also eligible for resynchronization therapy.

"CMS did the medical community a big favor. It gave them very broad coverage for prophylactic ICD implantsmaybe broader than they might have," said Bigger. The criteria leave a lot of the patient selection up to the physician. "It's a wonderful position to be in, but I think we have to use it responsibly."

Anybody who does exercise testing for coronary disease in their office could do this.

"There are low-risk subsets among those identified under the coverage decision," perhaps a quarter to a third of the total, Bigger said, "that really don't have much chance of benefiting from one." Society unnecessarily bears the cost in such cases, and "as far as the patient's concerned, it's more of an aggravation than a benefit."

It's the TWA test's tiny false-negative rate "that makes it extraordinarily powerful in identifying these low-risk groups among those covered by the CMS decision," Bigger said. "I think it will give physicians the confidence to use it and make a decision not to implant [an ICD] when the impulse is to be safe and put one in."

If the test is ever included within the reimbursement criteriaand "I think we're a long way from that," Bigger saidit would be fairly easy to implement. In the trial, patients were maintained on their drug therapy, which included beta blockers in 81%, which "made it very convenient to use in outpatients," he said. "Anybody who does exercise testing for coronary disease in their office could do this."


TWA compared with, combined with LVEF

The population consisted of 549 mostly male patients in sinus rhythm and an LVEF <40% (average 25%) who were in NYHA class 1-3, divided nearly evenly between those with ischemic and nonischemic cardiomyopathy.

The baseline TWA test was abnormal in 66% of patients. Over the next two years, the primary end point, defined as all-cause mortality or nonfatal sustained ventricular arrhythmias, occurred in 10.7% of patients. But event rates varied considerably by TWA results and LVEF.

Predictive value of TWA vs LVEF


Parameter

TWA

LVEF

2-year primary-end-point rate (%), abnormal test result*

15.0

12.0

2-year primary-end-point rate (%), normal test result*

2.5

7.3

Abnormal test result, HR for primary end point (95% CI)

6.5 (2.4-18.1)

1.8 (0.9-3.7)

p for HR

0.0003

0.1049

False-negative rate (%)

2.1

6.3

Web Bug from images/pixel.gif

*Abnormal LVEF <30%, normal LVEF >30%

On its own, TWA surpassed LVEF as a predictor of the primary end point, Bigger observed when presenting the findings. Patients with an LVEF of 31% to 40% had a high risk "and, if risk-stratified with T-wave alternans, probably in the future [many could] be candidates for ICD prophylaxis." He said the TWA test is "dominant" when the two risk indicators are used together; still, their combination can disclose "a group that's at very high risk relative to the whole group or an ultra-low-risk group that is negative for both variables." The latter group, he said, "probably can be managed conservatively and don't have much to gain from having a prophylactic ICD implantation."

Event rates by paired TWA and LVEF test results


Paired results

n

Primary end point, 2 years (%)

TWA normal, LVEF 31%-40%

55

0.0

TWA normal, LVEF 30%

134

3.5

TWA abnormal, LVEF 31%-40%

89

11.8

TWA abnormal, LVEF 30%

271

16.1

Web Bug from images/pixel.gif


Does QRS interval influence the TWA test?

Although at least one prior study has suggested that TWA isn't predictive of death and ventricular arrhythmias among patients with a prolonged QRS interval,[5] according to the common definition also used in Bigger's study, retrospective data from the TWA in HF trial suggests the opposite.

"Regardless of QRS duration, those with an abnormal T-wave-alternans test have a markedly higher two-year event rate," Levin said during her presentation. Patients with an abnormal TWA test by itself, she said, "had a 650% increased risk of death or [nonfatal] sustained ventricular arrhythmia compared with those with a normal test," suggesting its predictive value is "robust" regardless of QRS duration.

Although QRS prolongation alone similarly increased the risk, adding QRS to the TWA test appeared to stratify the patients more precisely.

Hazard ratios (95% CI) for primary end point at 2 years, abnormal TWA vs QRS prolongation


Parameter

TWA

QRS

p

Abnormal test result, HR*

6.5 (2.4-18.1)

6.2 (2.2-17.2)

0.33

Web Bug from images/pixel.gif

*Abnormal QRS >120 ms, normal QRS <120 ms

Event rates by paired TWA result and QRS duration


Paired test results

n

Primary end point, 2 years (%)

TWA normal, QRS 120 ms

150

1.7

TWA normal, QRS >120 ms

39

5.3

TWA abnormal, QRS 120 ms

244

13.6

TWA abnormal, QRS >120 ms

111

17.1

Web Bug from images/pixel.gif

To download tables as slides, click on slide logo below

The findings from both analyses should be explored in the context of ICD trials, in which patients have TWA, LVEF, and QRS intervals assessed but receive ICDs regardless, Bigger said when interviewed. A few such studies are ongoing, he noted, including the international Alternans Before Cardioverter Defibrillator (ABCD) trial.


The TWA in HF study was partially supported by a grant from Cambridge Heart. Bigger and Levin had no potential conflicts of interest to disclose. Another coauthor, listed as participating in both analyses, reported participation with the Cambridge Heart speakers' bureau.

Web Bug from images/pixel.gif

 



Web Bug from images/pixel.gif

Web Bug from images/pixel.gif

Web Bug from images/pixel.gif

Sources

1.        Bigger JT, Parides MK, Steinman RC, et al. Relative predictive value of T wave alternans and left ventricular ejection fraction for death and sustained ventricular arrhythmias in patients with left ventricular dysfunction. 2005 Heart Rhythm Society Scientific Sessions; May 4-7, 2005; New Orleans, LA. Abstract AB27-2.

2.        Levin SB, Bigger JT, Steinman RC, et al. Predictive power of T wave alternans in patients with left ventricular dysfunction and QRS prolongation. 2005 Heart Rhythm Society Scientific Sessions; May 4-7, 2005; New Orleans, LA. Abstract AB27-3.

3.        McClellan MB, Tunis SR. Medicare coverage of ICDs. N Engl J Med 2005; 352:222-224.

4.        Bloomfield DM, Steinman RC, Namerow PB, et al. Microvolt T-wave alternans distinguishes between patients likely and patients not likely to benefit from implanted cardiac defibrillator therapy: a solution to the Multicenter Automatic Defibrillator Implantation Trial (MADIT) II conundrum. Circulation 2004; 110:1885-1889.

  1. Rashba EJ, Osman AF, MacMurdy K, et al. Influence of QRS duration on the prognostic value of T wave alternans. J Cardiovasc Electrophysiol 2002; 13:770-775.

Web Bug from images/pixel.gif



Web Bug from images/pixel.gif

Web Bug from images/pixel.gif

Web Bug from images/pixel.gif

Related links

Decision memo for implantable defibrillators

Fine print in expanded ICD reimbursement criteria calls for caution
[HeartWire > Heart failure; Feb 1, 2005]

T-wave-alternans test shows it can screen out low-risk nonischemic ICD candidates
[HeartWire > Heart failure; Dec 3, 2004]

T-wave alternans again shows promise as risk stratifier for ICD candidates
[HeartWire > Heart failure; Oct 4, 2004]

CMS expands ICD reimbursement criteria, with conditions
[HeartWire > Heart failure; Sep 29, 2004]

Mental stress induces cardiac electrical instability as measured by T-wave alternans
[HeartWire > News; Mar 22, 2004]

The experts on SCD-HeFT: Implement now, but seek more discriminating ICD patient-selection criteria
[HeartWire > Heart failure; Mar 10, 2004]

T-wave-alternans-negative MADIT II patients may not need ICDs
[HeartWire > News; Jul 10, 2003]

Positive T-wave alternans an effective predictor of outcomes in patients with congestive heart failure
[HeartWire > News; Mar 31, 2003]

AMA to give microvolt T-wave alternans testing a permanent CPT code
[HeartWire > News; Mar 12, 2001]

T-wave alternans a noninvasive measure of future arrhythmias in congestive heart failure
[HeartWire > News; Aug 22, 2000]

New system for microvolt T-wave alternans measurement gets FDA approval
[HeartWire > News; Jun 15, 2000]

Web Bug from images/pixel.gif


Access to theheart.org is free, and is available only to healthcare professionals, media representatives, and medical librarians. To register as a user of theheart.org, click:
http://www.theheart.org/