Echo-CRT Subgroups With Heart Failure and Narrow QRS Still Show No Benefit From CRT

Deborah Brauser

May 28, 2015

SEVILLE, SPAIN — Echoing results from its parent study, additional subgroup analysis from the Echo-CRT trial again showed no benefits and possible harm from cardiac resynchronization therapy (CRT) for patients with heart failure and narrow-QRS duration[1].

Whereas the original randomized study examined HF patients with evidence of ventricular dyssynchrony and QRS intervals of <130 ms, the new research assessed those at 120 to 130 ms as well as at <120. As before, the new findings showed that "CRT-on" groups, regardless of interval duration, did not have significantly improved outcomes vs the CRT-off groups. In addition, there were trends for increased device-related complications.

The results were presented at a late-breaking clinical-trial session here at the Heart Failure Congress 2015 of the European Society of Cardiology Heart Failure Association and simultaneously published in the European Heart Journal.

"We wanted to see if these specific groups would be able to profit from CRT, but it turns out this was not the case," lead author Dr Jan Steffel (Heart Center at University Hospital Zurich, Switzerland) told heartwire from Medscape.

"Chances are, this is the final nail in the coffin for using this in these patients. And if you put this together with everything we have and with other large trials, all of it shows no benefit at all," said Steffel. He added that although he isn't sure whether all of this will change guidelines, "I can tell you from my personal practice, I've become very careful in terms of putting CRT into these patients."

Deep Dive Into Echo-CRT

As reported at the time by heartwire , the original, multicenter Echo-CRT trial included patients from 115 centers in the US, Canada, Europe, Australia, and Israel. All had QRS durations <130 ms, had echocardiographic evidence of LV dyssynchrony, and were implanted with CRT. They were then randomly assigned to CRT-on or CRT-off groups. The trial was prematurely terminated "due to futility" after enrolling and following 809 patients for a mean of 19 months and showing a relative increase in all-cause mortality.

Dr Jan Steffel

"As a result of Echo-CRT, current guidelines now recommend against the use of CRT in patients with a QRS of less than or equal to 120 ms," said Steffel. "However, it was unclear whether patients with the longest QRS durations in Echo-CRT might derive some benefit. And that question is important because these patients are currently eligible to receive CRT."

So in the current analysis, the researchers examined the subgroups of participants with durations of 120 to 130 ms (n=139, mean age 61.8 years, 79% men) and of <120 ms (n=661, mean age 57.2 years, 71% men). They found no significant differences between CRT-on or CRT-off status in either QRS-duration group for the primary efficacy outcome, which was a combination of death from any cause or first CHF hospitalization.

The primary safety outcome of device-related complications was found in 14.1% of the QRS <120 ms CRT-on group vs 7.3% of the CRT-off group; and in 12.3% vs 6.8%, respectively, in those with QRS 120 to 130 ms. But again, this was not statistically significant.

The Search Continues

When discussing study limitations, Steffel noted that the small number of patients in the 120-130–ms group kept them from conducting meaningful subsubgroup analyses in women, nonischemic patients, and others who may have benefited.

The main takeaway, however, is that "our patients didn't profit, which is really a shame because there's not a lot of other things we can offer them," he said. "Together with the consistent data emerging from other large-scale randomized trials, as well as meta-analyses, these findings may have implications for further guidance regarding the optimal QRS-duration cutoff for CRT."

Assigned discussant Dr Fausto J Pinto (Lisbon University Medical School, Portugal) said that, like the original Echo-CRT trial, this subanalysis was "very important," even though "there was no evidence at all" of any benefit from CRT in patients with QRS <130. "If anything, it was on the opposite side and contradicted its use," he said.

"I think it's important to continue the search for new methods of assessment because we need to improve the way we select patients," added Pinto. "There are still some gaps missing here. In most patients who don't respond or have negative results, it's not clear exactly why."

He noted that perhaps another study is now needed with larger numbers. "And we need to do these subgroup analyses to help us find the exact population that benefits from CRT, to bring up questions and to potentially open up new opportunities."

Steffel reported having received consultant and/or speaker fees from Amgen, AstraZeneca, Bayer, Biotronik, Biosense Webster, Boehringer-Ingelheim, Boston Scientific, Bristol-Myers Squibb, Daiichi-Sankyo, Cook Medical, Medtronic, Novartis, Pfizer, Roche, Sanofi, Sorin, and St Jude Medical. He has also received grant support through his institution from Bayer Healthcare, Biotronik, Daiichi Sankyo, Medtronic, and St Jude Medical. He is also codirector of CorXL.


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