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Viability testing does not find heart failure patients who would benefit from PCI in REVIVED-BCIS2

PCI did not improve prognosis or LV recovery in ischemic cardiomyopathy, regardless of baseline viability.

NEW ORLEANS, LA – Regardless of what the viability tests show, there is no significant benefit of PCI compared to optimal medical therapy in patients with compromised left ventricular function and extensive coronary artery disease, according to a new analysis from the REVIVED-BCIS2 study.

PCI did not improve prognosis or LV recovery regardless of baseline vital signs, nor was the presence of dysfunctional but viable myocardial segments associated with patient prognosis or recovery. The deep dive into the study, presented earlier this week at the American College of Cardiology/World Congress of Cardiology (ACC/WCC) 2023 meeting, challenges some long-held beliefs about myocardial overwintering, the investigators say.

“I think it challenges it because we’re now using viability tests as a predictive marker for hibernation,” said REVIVED-BCIS2 lead researcher Divaka Perera, MD (King’s College London, England) during a packed clinical research session. “Of course, this is based on the assumption that we can select the parts of the ventricle that recover, [and thus] the patient who will have an LV recovery. We’ve shown that using the metrics we currently use [viability] does not predict LV recovery. I think we need to question the paradigm. Hibernation as we know and use it no longer seems to make sense in clinical practice.”

When asked whether viability testing should be used to identify patients who might benefit from revascularization, Perera said the answer was a resounding no. “There is absolutely no evidence from it or from the STICH data that it predicts a population of patients who will benefit,” he said.

Characterization by viability assessment does not allow us to select a group of patients who would benefit from PCI versus drug therapy. Divaka Perera

Sunil Rao, MD (NYU Langone Medical Center, New York) agreed that the analysis challenges current concepts and definitions of the hibernating myocardium.

“The whole idea behind hibernating the myocardium is that it is dysfunctional but still viable because revascularization or restoration of blood flow should bring it back to normal,” Rao told TCTMD. “And the observational data confirms that. There’s Raymond Kim’s article in the New England Journal of Medicine years showing that there was an association between revascularization and improved function in those dysfunctional segments with 50% or less scarring. What’s remarkable about REVIVED is that they kind of tested it head-on.”

Rao said doctors are struggling with whether or when to revascularize patients with extensive stable coronary artery disease and compromised LV ejection fraction. While the 5-year results from STICH showed no benefit of CABG over drug therapy, it did show a survival benefit with surgery by 10 years. In REVIVED, PCI did not reduce the incidence of all-cause death or heart failure hospitalizations compared to guideline-compliant medical therapy. There is also ISCHEMIA and COURAGE that also need to be considered

“If the idea is to revascularize just to improve ejection fraction, I don’t think you’re going to get there,” Rao said. “If they have symptoms, then that’s probably the reason for revascularization. The question is, should we do feasibility testing to guide these decisions? I agree with Divaka [Perera]—The routine use of viability testing is not supported by these data. Then the question arises, with whom should we use viability tests? I don’t think we know the answer to that.”

Can’t find the Goldilocks zone

Presenting the new results, Perera, like Rao, said observational data had led many to believe viability testing was a useful tool to identify those who would benefit from revascularization. Patients with viable myocardium—which was defined as yes/no in these early studies—appeared to cope much better with revascularization than patients without viable myocardium. However, data from the STICH study challenged the viability hypothesis, as investigators reporting the presence of a viable myocardium did not predict the benefit of CABG surgery in patients with ischemic cardiomyopathy.

Given these conflicting results, the researchers set out to better understand the importance of viable myocardium in the REVIVED cohort, including whether viability predicted event-free survival, response to PCI, or optimal medical therapy, and whether it was associated with a Left ventricular recovery was associated. In turn, they also wanted to assess whether left ventricular recovery was associated with event-free survival. The majority of patients underwent viability testing with cardiac magnetic resonance imaging (CMR), while dobutamine stress echocardiography (DSE) was used in approximately 20% of patients.

In viability testing, myocardial segments were initially classified as normokinetic or dysfunctional, with the dysfunctional segments further classified as dysfunctional-viable, which is a correlate of the myocardium at rest, or non-viable. Viable segments were defined as those with contractile reserve at DSE or CMR late gadolinium enhancement ≤ 25%.

When I get an MRI and it shows me a lot of scarring in the left ventricle, I worry about that patient. Kevin Bainey

Regardless of treatment allocation, patients with more viable myocardium were less likely to die or be hospitalized for heart failure, while the presence of a more dysfunctional but viable myocardium was not significantly associated with event-free survival. Likewise, there was no association between the extent of dysfunctional but viable segments and LV recovery, although LV recovery itself was associated with risk of death or hospitalization for heart failure. Those who had an increase in ejection fraction above the median change had a 38% reduced risk of the primary endpoint compared to those who had less LV recovery (P = 0.029).

Scar burden was also tracked with results: for every 10% increase in scar volume, there was an 18% greater risk of death or hospitalization for heart failure (HR 1:18; 95% CI 1.04-1.33).

“If you characterize the myocardium in terms of scarring or the extent of non-viable myocardium, it is very predictive of prognosis and likelihood of LV recovery, regardless of left ventricular ejection fraction at baseline,” said Perera.

Regarding the effects of PCI versus guideline-based medical therapy (GDMT) in the study, there was no difference in outcomes after treatment assignment based on amount of overwintering myocardium or scar load. Likewise, the extent of scarring or dysfunctional but viable myocardial segments at baseline was not helpful in predicting whether PCI or GDMT would improve LV recovery over tertiles of patients with dysfunctional but viable segments at baseline.

“Characterization by viability assessment does not allow us to select a group of patients who would benefit from PCI versus drug therapy,” Perera said. “There is no ‘Goldilocks’ zone that we have identified.”

Benefits of identifying myocardial scars

Speaking to TCTMD, Rao said that using CMR to identify scar strain can be helpful because “it’s clearly prognostic” and can help inform conversations with the patient and potentially help them better adhere to medications, for example. “Beyond that, I think it’s a really confusing time,” he said. Myocardial scars may reflect previous cardiovascular events, the extent of their CAD, and likely the duration of their disease. “In a way, it’s not surprising that the scar in and of itself has no prognostic significance,” he said. “What’s surprising is that it didn’t seem to matter whether you were on drug therapy or PCI.”

Kevin Bainey, MD (Mazankowski Alberta Heart Institute/University of Alberta, Edmonton, Canada), who was not involved in the study, said the prognostic implications of scarring are an important finding that makes biological sense. “As a doctor, if I get an MRI and it shows me a lot of scarring in the left ventricle, then I worry about that patient,” he said. “It might make me think about an ICD [implantable cardioverter-defibrillator] for prevention. This could change a physician’s thought process on how best to risk stratify this patient over the long term.”

One of the limitations, he said, is that the researchers used stress echo and CMR as opposed to PET imaging, which is what most people use to assess viability.

Perera does not think viability testing should be discarded entirely, but stressed that they should not focus on dysfunctional segments to identify patients who would benefit from PCI or those with the potential for LV recovery. “Instead, useful information is embedded in these very viability tests that we do: scarring and non-viable myocardium,” he said, noting that irreversible injury remains a strong predictor of prognosis. “Whether we can use this for better risk stratification of patients or apply it to ICD therapy etc. needs to be tested in future studies.”