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ALPHA lends
support for TWA testing in nonischemic HF
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March 25, 2007 |
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New
Orleans, LA - A new study of the noninvasive microvolt
T-wave alternans (TWA) test in patients with nonischemic cardiomyopathy shows
that the one third of patients who test normal will likely not benefit from an
implantable cardiac defibrillator (ICD).
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Dr Gaetano M De Ferrari |
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Dr
Gaetano M De Ferrari (San Matteo Hospital, Pavia,
Italy) presented the findings of the T-Wave Alternans in Patients with Heart
Failure Trial (ALPHA) during a late-breaking session here today. He said:
"The negative predictive value of the test is the most important finding
of this study. Patients with a normal TWA test have a very good prognosis and
are unlikely to benefit from ICD therapy."
Panelists at the
late-breaking session commended De Ferrari on his study, which they said
"was difficult to do." But they pointed out that the group of
patients with abnormal TWA tests appeared to be sicker and therefore wondered
whether this could have contributed to the findings. De Ferrari said this was
true to a certain extent, but multivariate analysis controlling for confounding
factors still revealed a significant difference between the two groups in terms
of the primary end point—a combination of cardiac death and life-threatening
ventricular arrhythmias.
A pure primary-prevention population
De Ferrari explained
that patients with heart failure have a high risk of mortality, 50% of which is
attributable to sudden death. "However, we implant many ICDs that will
never work. We need to better refine the strategy to identify which patients
need the device, for medical, psychological, and economic reasons."
The TWA test monitors
for minute beat-to-beat variations in the electrocardiographic T-wave during exercise
stress testing and is performed using the Cambridge Heart/St Jude Medical's
ECG-analysis algorithm for the risk stratification of ICD candidates.
De Ferrari said that
although there is considerable evidence that TWA testing is quite effective at identifying
ischemic patients at high risk of sudden death, "the data regarding the
role of this technique in patients with nonischemic heart failure are limited
and conflicting. The search for reliable risk stratifiers [in this patient
population] has been very frustrating."
In the ALPHA study,
446 NYHA stage 2 and 3 heart-failure patients with cardiomyopathy of
nonischemic origin and left ventricular ejection fraction (LVEF) of less than
40% underwent a TWA test and were followed for 18 to 24 months to assess the
rates of the combined primary end point, as well as the secondary end points of
total mortality and a combination of arrhythmic death, life-threatening
arrhythmias, and hospitalization.
Patients were excluded
from entering the study if they had a pacemaker or ICD implanted: "We
wanted to have a pure primary-prevention population," De Ferrari
explained.
Abnormal test linked to fourfold risk of
death, arrhythmias
Of the 446 patients,
65% (n=292) had an abnormal TWA test and 154 had a normal result. According to
convention, patients with TWA findings labeled "indeterminate" (n=92)
were combined with those who had an abnormal TWA test.
Patients with an
abnormal TWA test had a fourfold higher risk of the primary end point—cardiac
death and life-threatening arrhythmias (hazard ratio 4.01; p=0.002), De Ferrari
said. They also had a fourfold higher total mortality (HR 4.60; p=0.002) and a
fivefold higher risk of arrhythmic death, life-threatening arrhythmias, and
hospitalization (HR 5.53; p=0.004).
Currently, "all
patients with stage 2 and 3 disease with LVEF less than 35% are considered
candidates for an ICD. The ALPHA study strongly suggests that one third of
these patients will have a normal TWA test and will not benefit from the ICD.
Knowing this, we are able to better treat the two thirds of patients that
really need the device," De Ferrari said.
Events during follow-up
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VT=ventricular tachycardia; VF=ventricular
fibrillation
Provocative but provisional data Both panelists at the
late-breaking session congratulated De Ferrari on the trial but pointed to
baseline differences between the two groups. "These data are provocative
but provisional because of the imbalances between groups," said Dr
Douglas L Mann (Baylor Heart Clinic, Houston, TX). De Ferrari agreed that
those with an abnormal TWA test were, on average, 2.5 years older; slightly
more were in NYHA class 3 and had a worse quality of life and had worse LVEF;
and there were differences between them in terms of digitalis treatment.
"But we did a multivariate analysis controlling for these baseline
differences and we still found a significant hazard ratio of 3.2," he
noted. Asked by heartwire
what he thought the implications of his study were, De Ferrari said only about
13% of patients who needed ICDs in the US actually got them. "We are not
getting to the patients the guidelines suggest we can get to. This is clear.
This test is very helpful in identifying the population from whom, for the time
being, we can withhold ICDs."
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Dr
Mariell Jessup (Hospital of The University of Pennsylvania,
Philadelphia), the other panelist at the late-breaking session said:
"These are very intriguing data. It's not clear to me why the
implementation of ICDs is so low. But it's hard to picture how this is going to
be solved by TWA testing. . . . There are many, many reasons why people aren't
putting defibrillators into patients whom they think might benefit."
Future studies will have to monitor shocks
Mann said the ALPHA
findings will need to be confirmed, and De Ferrari agreed. However, the Italian
researcher pointed out that large numbers of patients would be required.
"We could look at people with EF below 35% and a positive TWA who are
implanted with ICDs and then also a study in which those with a negative TWA
result are randomized either to ICD or conventional treatment. I don't know if
this is possible given the guidelines, but if you could show no survival
difference between the implanted and nonimplanted patients if they have a
normal TWA test, that would be great."
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Mann said another way
to assess the situation would be to follow all people with ICDs for shocks, do
a TWA test, and then follow them longitudinally to see how predictive the test
is. Again, De Ferrari agreed but pointed out that "the number of shocks
outnumber the number of sudden deaths by a factor of 3 to 1. That is the
advantage of this study—most of our patients did not have ICDs. This is very
difficult to repeat. In the future we will have to rely on shocks, which are
not the same as sudden death."
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