Doubts About CMR for Targeting ICDs in Nonischemic Systolic Heart Failure

January 29, 2020

The 2016 multicenter DANISH trial questioned whether the implantable cardioverter-defibrillator (ICD) should be routinely recommended in nonischemic systolic heart failure (HF). The trial saw no overall survival advantage of ICD therapy, but hinted that a more targeted approach to selecting patients for devices might be more effective.

Now a DANISH substudy raises its own questions about the usefulness of a common test many believe can guide such a targeted approach.

In a single-center cohort from the trial, evidence of myocardial fibrosis by late gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR) imaging predicted all-cause mortality, in line with a lot of previous evidence.

But such signs of myocardial scarring, which evidence suggests can promote ventricular arrhythmias, did not also predict improved survival with ICDs — which could only happen through prevention of arrhythmic death.

That LGE didn't predict ICD benefit "suggests that the increased risk associated with LGE is not altered by ICD implantation and that the mechanism for increased mortality in these patients is not primarily shockable ventricular arrhythmias," notes the DANISH subanalysis report, published December 24 in the American Heart Journal.

The findings are only suggestive, given the small size of the study. Still, they are consistent with LGE on CMR imaging as "a marker of overall disease severity and all-cause mortality, as found previously, but not for shockable arrhythmic death," write the authors, led by Marie Bayer Elming, MD, PhD, Rigshospitalet, Copenhagen.

There has been much hope that LGE would improve the selection of patients with nonischemic heart failure who might benefit from ICD implantation; "however, our study does not support this hope," Elming told theheart.org | Medscape Cardiology.

"There were very few sudden-cardiac-death (SCD) events, and therefore the data are not sufficient to conclude whether LGE can be used for SCD risk stratification," she said by email.

The analysis included 236 patients with analyzable LGE on CMR scans at one DANISH center, a subgroup of the total cohort of 1116 patients with nonischemic HF and a left ventricular ejection fraction (LVEF) of 35% or lower who had been randomized to medical therapy with or without an ICD.

In adjusted analysis, the risk for death from any cause, the primary end point, was significantly increased over an average 5.3 years for patients who showed LGE at CMR (hazard ratio [HR], 1.82; 95% CI, 1.002 - 3.29; P = .049).

But such risk was not significantly different between ICD recipients and those without devices, among both the 113 patients with LGE by CMR and, separately, the 123 without the CMR sign of fibrosis, regardless of whether the patients were also receiving cardiac resynchronization therapy (CRT).

The adjusted risk for a secondary arrhythmic end point (a composite of sudden cardiac death, resuscitated cardiac arrest, sustained ventricular tachycardia, and appropriate ICD shock) was more than doubled in patients with LGE by CMR (HR, 2.23; 95% CI, 1.12 - 4.47; P = .02).

"There's certainly a lot of data that areas of scar in patients with nonischemic cardiomyopathy can be the source of ventricular arrhythmias, so it makes sense that if scar is detectable by magnetic resonance imaging, it should be associated with an increased risk of arrhythmias," William G. Stevenson, MD, not associated with DANISH, told theheart.org | Medscape Cardiology.

And, "we've long recognized that ventricular arrhythmias are markers of increased total mortality and increased risk of heart failure hospitalizations," said Stevenson, from Vanderbilt University Medical Center, Nashville, Tennessee. "It's not a surprise, then, as has been well shown, that scar is associated with an increase in mortality."

Therefore, the use of LGE by CMR to identify patients with nonischemic systolic HF most likely to benefit from ICDs "would seem to be a reasonable approach that needs to be tested."

So the results of the current study "are a bit surprising in that regard, because I would have expected to see more benefit in the patients who have scar," he said.

"I think the study is underpowered to be able to show a benefit of the defibrillator," he added. Scar was indeed related to arrhythmic risk, "it just wasn't associated with a high enough risk in this relatively smaller number of patients to where a defibrillator could be shown to be beneficial."

Also, they were at increased risk for both arrhythmic and nonarrhythmic mortality, and "when you give them a defibrillator, you're not doing anything to address the nonarrhythmic causes of death," Stevenson said.

"This is, I think, a sign of a wonderful success story — that with present therapy for heart failure and cardiomyopathy, and with resynchronization therapy, survival has gotten better and sudden death rates have fallen. But that makes it very hard to show a benefit in this population from a therapy that only addresses arrhythmias."

DANISH was supported by Medtronic and St. Jude Medical. Elming declares she has no conflicts of interest. Disclosures for the other authors are in the report. Stevenson has previously disclosed receiving research grants from Novartis, consulting or serving on an advisory board for Abbott, and travel expenses or meals from Novartis and St. Jude Medical.

Am Heart J. Published online December 24, 2019. Abstract

Follow Steve Stiles on Twitter: @SteveStiles2. For more from theheart.org | Medscape Cardiology, follow us on Twitter and Facebook.

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