Revascularization’s Benefits in HFrEF Linked to Gains in LV Function

For patients who have heart failure with reduced ejection fraction (HFrEF) and coronary artery disease, improvements in LV function after revascularization are linked to better long-term outcomes, an analysis of more than 10,000 US veterans has found. The strengths of this association were greater with PCI and didn’t reach significance with CABG.

The results were published online earlier this week in Circulation: Cardiovascular Interventions.

Raghava S. Velagaleti, MD, MPH (VA Boston Healthcare System, MA), said their study addressed a lot of unknowns: whether revascularizing patients with HFrEF would improve LV systolic function, whether this in turn would improve outcomes, and finally, whether PCI might offer benefits in this setting.

“The surprising thing is not only did percutaneous coronary intervention have a benefit, but it seemed to have a benefit at least as good as bypass surgery, if not maybe even better,” he told TCTMD. “This concept that revascularization would lead to an improvement in ejection fraction, which would then lead to an improvement in clinical outcomes: it is intuitive, it has been assumed in the past, but I think for the first time that three-level link has been made with our data.”

US and European heart failure guidelines, based on data from the randomized, controlled STICH trial, support surgical revascularization plus guideline-directed medical therapy in select patients with ejection fractions of 35% or less, as do US and European revascularization guidelines. No such data exist for PCI, though the REVIVED-BCIS2 trial on the topic is ongoing.

VA Database: 1995-2010

Using data from the Veterans Affairs healthcare system, the researchers identified 10,071 veterans (mean age 67 years; 1% women; 15% nonwhite) with heart failure and ejection fraction < 50% who underwent a first coronary revascularization between 1995 and 2010. Mean ejection fraction was 35%.

Three-quarters of the patients received PCI, while one-quarter got CABG. Small though significant differences were seen between the two groups at baseline. The PCI group tended to be older, more likely to smoke, have higher blood pressure, and have higher creatinine. Compared to the CABG group, they also were less likely to receive statins and had a lower prevalence of diabetes.

If you improve your ejection fraction—however you get there—that’s a good thing. Ajay Kirtane

Mean follow-up duration was 5 years, with a maximum of 14 years. Half of the patients (56%) died during follow-up. Changes in ejection fraction were described as delta-EF, referring to the difference between values before versus after revascularization. Each 5% gain in delta-EF was linked to a 5% relative reduction in death and 10% decrease in days of heart failure hospitalization. Within the PCI subgroup, deaths decreased by a relative 6% and days of heart failure hospitalization by 6%.

Patients with the largest changes in ejection fraction had 27% lower mortality overall. Again, the reduction in death was slightly greater in the PCI group, at 30%. Heart failure hospitalization days for these patients were reduced by 40% both in the overall population and within the PCI subgroup.

For CABG alone, the differences in outcomes did not reach statistical significance.

Possible explanations are that follow-up duration was too short to capture an eventual survival benefit with CABG and that the older age of the CABG patients, as compared with the PCI patients, might have lessened the potential for benefit, the paper notes. “PCI, which does not have an early mortality penalty similar to CABG, may conceivably be a better option in terms of harmonized risk versus benefit in older patients with CAD and reduced EF needing revascularization; in younger patients and those with a lower comorbidity burden, CABG is likely still the preferred revascularization strategy.”

It’s also possible, the researchers add, that CABG and PCI have different mechanisms of benefit, where CABG’s effects are less tightly intwined with LVEF improvement.

Messages for Today’s Practice

Velagaleti said that, even though their study period ended more than a decade ago, the results are still relevant. In the years since then, “both revascularization modalities have only gotten better,” he observed, adding, “So one would expect that the benefit of revascularization in terms of improving systolic function would be at the very minimum the same, if not actually much better.”

However, he noted a caveat: “Obviously medical management has improved, too.” It’s not known if the difference in outcomes between revascularization and medical therapy, as shown in STICH specific to CABG, would narrow or stay the same, Velagaleti explained. “I think that remains to be seen.”

Another area for further research, he suggested, relates to the variability their study saw in who improved and to what degree. “Trying to identify particular patient subsets that would disproportionately benefit from revascularization [is] worth investigating, because obviously both CABG and PCI are procedures and they carry procedural risks, and there is a cost element to it,” he said, such that some patients might be better suited to medical management. Recent refinements in CV imaging might allow more detailed assessment of subtle LVEF changes, as well, said Velagaleti.

Trying to identify particular patient subsets that would disproportionately benefit from revascularization [is] worth investigating. Raghava S. Velagaleti

Ajay Kirtane, MD (NewYork-Presbyterian/Columbia University Irving Medical Center, NY), who did not take part in the study, said it confirms the idea that “if you improve your ejection fraction—however you get there—that’s a good thing. That’s the most important finding here.”

While it’s useful to see that validated, he agreed, what’s very challenging is determining the extent to which those LVEF changes are due to the revascularization itself. Other possible influences include the level of medical therapy a patient receives or whether they had presented with acute MI, he noted.

Kirtane also cautioned against drawing too many conclusions about the PCI versus CABG difference, given how close the CABG group came to statistical significance. “It’s directionally very similar,” he said, noting that for mortality the upper end of the confidence interval was just 1.01. Moreover, there’s evidence from other studies showing an advantage for CABG over medical therapy.

It’s not yet known whether this will hold true for PCI. Kirtane said that the REVIVED-BCIS2 trial, which could provide answers on this issue, will be released later this year.

David Tehrani, MD (Ronald Reagan UCLA Medical Center, Los Angeles, CA), and Arnold H. Seto, MD (Long Beach VA Medical Center, CA), in an accompanying editorial, agree that there’s been uncertainty over what is responsible for revascularization’s benefits in patients with dual diagnoses of CAD and HF: the reduction in cardiovascular events or the improvement in ejection fraction. Importantly, the latter “could also be attained through guideline-directed medical therapy,” they point out.

And though they specify several caveats to the study, the editorialists say it still provides valuable take-home messages.

First, it supports the idea that change in EF as a surrogate outcome measure “is both logical and reasonable as practitioners make decisions for clinical therapies (including placement of defibrillators) . . . in daily practice,” Tehrani and Seto write. “Second, this study provides further validation of revascularization in patients with stable coronary artery disease and ischemia and potentially argues for equipoise between PCI versus CABG in those with heart failure with reduced ejection fraction, where currently CABG is favored.”