Defibrillators Implanted Despite Test that Excludes Need

ANN ARBOR, Mich., Jan. 4 -- When a sophisticated electrocardiogram test appears to rule out the need for an implanted cardioverter-defibrillator (ICD) in ischemic cardiomyopathy, the results are frequently ignored, according to researchers here and Cincinnati.

As a result, perhaps 30% of ischemic cardiomyopathy patients who prove negative by microvolt T-wave alternans (MTWA) are given an ICD device anyway, even though the test reveals no increased risk of sudden death, the researchers reported in the January issue of the Journal of the American College of Cardiology.

T-wave alternans (TWA) refers to variability in the timing or shape of T-waves from beat-to-beat on the surface ECG. Recently, computerized filtering and analysis has allowed TWA on the order of microvolts to be detected -- ergo, MTWA.

The study found that the number of patients needed to treat with an ICD for two years to save one life was nine among MTWA non-negative patients, but it would require 76 implantations among MTWA-negative patients, according to a team led by Paul Chan, M.D., of the University of Michigan here and Theodore Chow, M.D., of the Ohio Heart and Vascular Center in Cincinnati.

The findings came from a prospective cohort of 768 patients with ischemic cardiomyopathy (left ventricular ejection fraction ?35%) and no prior sustained ventricular arrhythmia, of which 392 (51%) received ICDs. Patients, in sinus rhythm at the time of testing, came from seven outpatient cardiology clinics in Ohio and were enrolled from 2001 to 2004. The mean follow-up time was 27 12 months.

Propensity scores for ICD implantation on the basis of the variables most likely to influence defibrillator implantation were developed for each MTWA cohort. Multivariable Cox analyses that controlled for propensity score, demographics, and clinical variables evaluated the degree to which ICDs decreased mortality risk for each MTWA group.

In the study cohort of 768 patients, 514 patients (67%) tested MTWA non-negative (positive or inconclusive), while 254 (33%) tested negative.

In the MTWA non-negative group 317 (62%) had ICDs implanted, compared with 75 (30%) in the MTWA-negative group.

Of the non-negative patients who received an ICD, 55% were less likely to die in the follow-up period than those who hadn't gotten an ICD. The reduction, the researchers said, was mediated largely through prevention of arrhythmic deaths. In contrast, patients who tested MTWA-negative received a nonsignificant (15%) mortality benefit.

After multivariable adjustment, ICDs were associated with lower all-cause mortality in MTWA-non-negative patients (hazard ratio [HR] 0.45, 95% confidence interval [CI] 0.27 to 0.76, P =0.003).

However, the benefit was not significant for the 30% of MTWA-negative patients who received ICDs (HR 0.85, CI 0.33 to 2.20, P=0.73; for interaction, P=0.04), the researchers reported.

Multivariable Cox analyses for the entire cohort found a statistically significant difference in mortality reduction with ICD therapy when comparing those testing non-negative with those testing negative (P value for interaction term evaluating ICD mortality benefit by MTWA group = 0.038).

A 70% mortality benefit in MTWA-non-negative patients was largely mediated through a reduction in arrhythmic mortality (HR 0.30, CI 0.13 to 0.68, P=0.004). When confining the outcome to arrhythmic mortality, ICDs were associated with dramatic reduction in the non-negative group only, the researchers said.

Among the limitations of the study, they noted, were the potential for residual confounding present in all cohort studies, and the restriction of the study to patients with ischemic heart disease, leaving out those with acutely decompensated heart failure.

Furthermore, they said, MTWA can be used only in patients in sinus rhythm, so that the findings cannot be extrapolated to the 8% to 15% of trial patients with ischemic cardiomyopathy in atrial fibrillation or flutter.

Finally, the examination of whether ICD benefit differed by MTWA group was justified by a test for interaction that was significant with a prespecified P value of 0.10. The study, they said, may not have been sufficiently powered to detect a difference in outcome in the MTWA-negative group.

Turning to the cost of ICD treatment, the researchers wrote that ICDs have been shown to be modestly cost-effective at approximately ,000 per quality-adjusted life-year in patients with ischemic heart disease and left ventricular dysfunction.

It has been estimated, they said, that 32,000 patients annually are newly eligible for this therapy. A recent cost-effectiveness study showed that ICD therapy (compared with medical therapy) is associated with an incremental lifetime cost of about ,000 for each patient.

Full implementation of the recent Medicare and Medicaid decision to expand indications for ICD coverage would translate into an incremental annual cost of .9 billion (beyond best medical therapy) just to cover all the eligible patients for life, the researchers said.

Therefore the findings of this study, Drs. Chan and Chow wrote, "suggest that MTWA may be an effective risk stratification tool in identifying patients most likely to benefit from ICD therapy, with as many as one-third of patients deriving minimal benefit from prophylactic ICD implantation.

It might be possible, they said, for MTWA-negative patients to rescreen annually, although data on conversion rates are lacking.

"We caution," they wrote, "that our findings should not be overinterpreted as justification for using MTWA screening for ICD placement without subsequent validation in larger cohort studies or future randomized clinical trials."

Summing up, they said, the use of the MTWA test could potentially save a large part of the annual cost of implanting cardioverter defibrillators, but the use of the test must await further study.

The researchers disclosed that their study was funded in part by Medtronic.

In an accompanying editorial, Andrea Russo, M.D.., and Francis Marchlinski, M.D., of the University of Pennsylvania, wrote that although as many as one-third of patients may derive minimal benefit from device implantation, it is unclear when to screen patients after infarction and how often to repeat MWTA testing.

Also, they noted that since only 75 patients in the MWTA group received an ICD, the study may not have been adequately powered to detect a statistical difference in this cohort.

Inserting ICDs in all patients who currently meet guidelines, based on left-ventricular function, leads to implantation of devices in many patients who will never need them, they wrote. Not only does this affect costs, but a realistic assessment of potential adverse events and quality of life should be considered.

Furthermore, they said, one benefit of potentially avoiding ICD insertion in the negative-MTWA group is the possibility of increasing resources for newer yet-to-be-defined populations who may derive greater benefits.

But because of limitations of the current cohort study, subsequent validation in larger cohort studies or future randomized studies is definitely needed before MTWA can be used routinely as a screening test, they concluded.