MADIT-CRT: Avoid Apical LV Lead Position in HF Resynchronization Therapy

May 14, 2010

May 14, 2010 (Denver, Colorado) — Reaching the apex would be a laudable goal in most disciplines, but cardiac electrophysiology appears not to be one of them, at least when it comes to positioning left ventricular leads for cardiac resynchronization therapy (CRT).

In a follow-up analysis from the Multicenter Automatic Defibrillator Implantation Trial with Cardiac Resynchronization Therapy (MADIT-CRT), the rate of death or heart-failure hospitalization--the trial's primary end point--went up significantly for patients whose LV leads had been extended to the apex of the heart during implantation of the CRT system, compared with those with other LV lead locations.

MADIT-CRT, which tested the HF-device therapy in patients in NYHA functional class 1–2 who were at most only mildly symptomatic, saw a one-third drop in risk of the primary end point over about 2.5 years in patients who received a CRT device with a defibrillator compared with those getting a defibrillator-only implant [1]. As heartwire noted when the findings were formally reported, the benefit was driven by a 41% reduction in risk of heart-failure events; CRT had little apparent affect on mortality alone.

Dr Jagmeet P Singh

Based on the trial, an FDA advisory panel recommended in March that coverage of CRT be extended from patients in NYHA class 3–4 to include those with milder heart failure.

But MADIT-CRT also indicates that an apical LV lead position worsens outcomes, "suggesting that this lead location should actually be avoided in cardiac resynchronization therapy," Dr Jagmeet P Singh (Massachusetts General Hospital, Boston) said when presenting the analysis here at the Heart Rhythm Society 2010 Scientific Sessions.

In a discussion of the findings with reporters, Singh said the hypothesis had been that apical LV lead placement would have a detrimental effect on clinical outcomes in the trial, at least partly because that position puts the lead near the right ventricular lead, which can make the resynchronization less effective.

Not only was there a detrimental effect, he said, "we found that was that there was a huge difference [in outcomes] between apical lead placement and nonapical lead placement." The risk of the primary end point went up 64% and mortality rose 2.6 times with apical placement.

And although earlier studies had suggested that lateral-wall positioning of the LV lead worked better than other ventricular locations, he said, "we found that they really weren't that different." There were no significant outcomes differences for patients with lateral, anterior, or posterior LV lead placement.

I think the results can be extrapolated, with some degree of caution, to the heart-failure population as a whole, even to those who are fairly symptomatic.

"I think the results can be extrapolated, with some degree of caution, to the [heart-failure] population as a whole, even to those who are fairly symptomatic," he said, with the qualification that the effects of varying LV lead positions could be very different in "patients who are very sick and whose hearts are very dilated."

As Singh reported, the analysis included 799 patients from the trial who hadn't received any epicardial leads or undergone lead revision. The LV lead was positioned at the apex in 14% of patients and at the lateral, anterior, and posterior ventricular walls in 56%, 18%, and 12% of patients, respectively.

Patients with apical LV leads had a 21.8% rate of death or heart-failure hospitalization over the study's mean follow-up of 29 months; the rate was 12.1% for those with nonapical LV leads. The findings were independent of heart-failure etiology or whether there was left bundle-branch block.

The primary-end-point hazard ratio for apical vs nonapical lead placement was 1.64 (95% CI 1.05–2.58), p=0.030; the mortality-only hazard ratio was 2.59 (95% CI 1.28–5.25), p=0.008.

As the discussant following Singh's presentation of the analysis, Dr Michael R Gold (Medical University of South Carolina, Charleston) said its findings "are very contrary to our early understanding of data from past investigations suggesting that the left ventricular free wall is a much better place to put the lead than an anterior [location], at least in terms of acute hemodynamics. And it is those types of data that have really driven our almost obsession with trying to place the leads on the free wall. Now we're starting to question some of those tendencies of our practice." He said the COMPANION trial also showed no advantage to positioning the lead at the lateral wall with respect to change in NYHA functional class and quality of life.

This also suggests that there's probably not a sweet spot.

Singh said MADIT-CRT was "uniquely poised" to study the effects of lead position on CRT effectiveness because "it is the only study so far that has collected coronary venous angiography and chest X-rays, both [posterior-to-anterior] PA and lateral views, prospectively at the time of implantation." Moreover, lead positions on venograms and X-rays were identified at a core laboratory. Even COMPANION explored lead location retrospectively, and lead positions were determined by the implanting physicians, "which we know is less accurate" than using a core lab.

Commenting on another implication of the analysis, Singh observed that "there are already many patients who are nonresponders to CRT. Maybe we should look at those patients, and if their leads are in the apical area, then maybe we need to revisit where the lead is and give them a chance at another position for an enhanced response."

He speculated for reporters that perhaps 15% to 20% of LV lead placements may be in the apex. "A lot of physicians [believe] that putting the lead down as far as they can is safe, because they believe then the lead won't get dislodged."

But repositioning the LV lead "isn't a trivial procedure." If a patient isn't responding to CRT, he said, other potential causes, such as inadequate programming, should be ruled out before undertaking it.

Dr Bruce L Wilkoff

Commenting on the study for reporters, Dr Bruce L Wilkoff (Cleveland Clinic, OH) observed that for most symptomatic patients who receive CRT and then don't respond to it, "there is an identifiable reason." But lead position is only one of the potential reasons, he said. In such cases, "the stakes are high. You have to do something about it." Options may include changing the device programming, medications, or lead position. If it doesn't work, the risk of death within a year is 80%. "If you can fix it, then at least 80% are alive a year later. So it's a huge difference."

In wrapping up his comments about the MADIT-CRT analysis, Gold observed that the issue of lead position and outcomes "is more complicated than we thought. We now should at least acknowledge that we shouldn't abandon an implant if a good lateral-wall vein is not found."

Now there are "compelling data" that an anterior LV lead position can result in a good response, he said. "This also suggests that there's probably not a sweet spot, as very diverse lead positions are coming up with very similar outcomes for patients."

Singh discloses receiving research grants from and consulting or serving on an advisory board and participating in "lectures or educational symposia" for Boston Scientific, Medtronic, Biotronik, and St Jude Medical and participating in lectures or educational symposia for the Sorin Group.


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