Ischemic Cardiomyopathy Patients Can Benefit From Myocardial Unloading, Study Suggests

A small proportion of patients with ischemic cardiomyopathy show signs of improved myocardial structure and function following mechanical unloading with a continuous-flow left-ventricular assist device (LVAD), a new study has shown. The results suggest that improvements in structure and function after LVAD implantation are not limited to heart failure patients with nonischemic etiology, say investigators.

In 61 patients with ischemic cardiomyopathy, LVEF improved from 20% at baseline to 24% 6 months after LVAD implantation (P<0.05). Comparatively, in 93 patients with nonischemic etiology, LVEF increased from 17% pre-LVAD to 25% at 6 months (P < 0.01). In a subset analysis of patients who completed at least six months of LVAD unloading,  5% of patients with ischemic cardiomyopathy achieved a LVEF ≥ 40% compared with 21% of patients with nonischemic cardiomyopathy (P=0.034).

When adjusted for the baseline LVEF, the maximum LVEF achieved during the post-LVAD period did not significantly differ between the two groups. The LV end-diastolic and end-systolic volumes also decreased significantly, as did the LV mass index, in both groups after LVAD implantation.

The improvements in function and structure were maintained under increased loading conditions, specifically during serial “turn down” echocardiographic studies where patients received 30 minutes of the lowest LVAD support.

Given that patients with nonischemic and ischemic cardiomyopathy appear to both have the “potential for significant recovery” with mechanical unloading, “we propose that patients with ischemic cardiomyopathy who have experienced MI and have large areas of noninfarcted myocardium that remodeled over time could also be considered candidates for myocardial recovery protocols,” according to lead investigator James Wever-Pinzon, MD (University of Utah Health Sciences Center, Salt Lake City, UT), and colleagues.

Speaking with TCTMD, Srinivas Murali, MD (Allegheny Health Network, Pittsburgh, PA), who wrote an editorial along with Richa Agarwal, MD (Allegheny Health Network), said the data showing “recovery” with LVAD therapy ranges as high as 35% to 40% in Europe. In the United States, published reports suggest recovery following LVAD implantation is in the range of 8% to 10%.

“There might be reasons behind [the discrepancy],” he said. “It might have to do with the type of patients getting the implant. There might be differences in a candidate who gets an LVAD in the US versus those in Europe. The bottom line is that there are some patients where there is recovery of cardiac function and the challenge has been identifying those patients and identifying the way [to help] them recover maximally.”

Murali agreed with the investigators, noting that most published reports of recovered cardiac function and structure include patients with nonischemic cardiomyopathy. However, this paper shows that even in the ischemic population, there are patients who can recover. “Even though the prevalence might be lower compared with nonischemic patients, it does happen,” he said. “In other words, it’s not a phenomenon completely restricted to the nonischemic cardiomyopathy patients.”

Need for Prospective, Clinical Outcomes Studies 

In their paper, which was published online October 10, 2016, in the Journal of the American College of Cardiology, the researchers explain that ischemic heart failure patients are considered to have a worse “substrate” for LVAD-induced recovery because of myocardial scarring. However, as they point out, patients with acute MI, even those with a large anterior-wall MI, are often discharged from the hospital without heart failure symptoms only to return later to the hospital with heart failure caused by chronic remodeling.

In the editorial accompanying the study, Agarwal and Murali state that it’s possible there is considerable overlap in the myocardial substrate of patients with ischemic and nonischemic cardiomyopathy. The study, they suggest, asks physicians to “confront our own bias and expand the candidate population beyond the patient with nonischemic cardiomyopathy.” That said, there is still work to be done.    

For example, Murali noted that despite the improvement in structure and function observed in this analysis, clinical outcomes are lacking. While the turndown studies showed maintained LV function, this was not a prospective bridge-to-recovery study and no patients had the LVAD explanted. 

“Thus, postexplant clinical outcomes, arguably the most important piece of recovery investigations, are lacking from this study,” write the editorialists. “We may draw some useful insights from knowing that peak LVEF improvement can occur by 6 months, but without the event of device explant itself to corroborate these findings, the authors leave us with the lingering question over what recovery truly means for any patient with [heart failure], be they ischemic or nonischemic.”

Murali told TCTMD the heart-failure community needs a better definition of recovery so that heart-failure programs are speaking the same language when it comes to LVAD therapy. Currently, the Centers for Medicare & Medicaid Services’ approved indication for an LVAD is a patient with stage D heart failure. Full recovery might be defined as complete recovery from symptoms, improved functional class, molecular and structural improvements, greater exercise tolerance, increased LVEF (≥ 45%), and device explantation, said Murali.

Partial recovery is also possible, with patients shifting back along the spectrum from end-stage heart failure (stage D) to stage C (heart failure with symptoms) or stage B (without symptoms), he added.

Given the higher rates of recovery in the nonischemic population, the editorialists urge staying committed to this group and even ramping up efforts with mechanical unloading. Regarding heart failure in general, the aspirational goal is an eventual cure, which might be possible through the “synergistic combination of LVAD unloading, traditional medical therapy, and newer regenerative therapies,” they write. “Recovery should mean a return to native heart function with reversal of myocardial biology and dysfunction to the extent that one can live reasonably free from heart failure.”