Changes in Cardiac Damage After AVR Tied to 2-Year Outcomes

PARIS, France—Patients with more-severe cardiac damage prior to undergoing aortic valve replacement are more apt to die in the 2 years after their procedure, data from the PARTNER trials show. What’s more, changes in the extent of that extravalvular damage at 1 year also impact 2-year mortality risk, investigators say.

The findings, with Philippe Généreux, MD (Morristown Medical Center, NJ), as lead author, were published today in the Journal of the American College of Cardiology to coincide with their presentation at EuroPCR 2022.

In 2017, Généreux and colleagues published an anatomy-based classification system for cardiac damage prior to AVR, linking baseline damage to outcomes. This time around, the researchers “characterized the evolution and the progression and regression of cardiac damage after aortic valve replacement,” Généreux told TCTMD.

Aortic valve disease doesn’t exist in isolation, he explained. “Even if you fix the valve and improve [its function], you still have to work on extravalvular cardiac damage. It’s not infrequent that you see patients that have great results after the TAVR or surgical AVR but still come back to the hospital with heart failure, A-fib, RV dysfunction, etc, etc.”

Aortic valve replacement, when it’s done late, is not reversing the damage. Maral Ouzounian

The message from this analysis is that “maybe we need to intervene earlier before cardiac damage is present,” he said, emphasizing that waiting too long can have consequences. Another takeaway is that this presents an opportunity to optimize therapy “upstream before the AVR and also downstream after the AVR,” Généreux advised.

Maral Ouzounian, MD, PhD (Toronto General Hospital, Canada), who didn’t take part in the research, said the paper is important and likely to be impactful.

What these data show is that “very few patients are coming without extravalvular damage. . . . This is quite late in the game,” Ouzounian told TCTMD. Also striking is the finding that “aortic valve replacement, when it’s done late, is not reversing the damage,” she noted. “A lot of them got worse or stayed the same, and I think that goes against what is common thinking about aortic valve disease—that by the time patients become symptomatic, you do AVR and their cardiac function and outcomes will improve.”

Patients should be referred earlier for treatment, Ouzounian stressed, and “we should really not be only focusing on the aortic valve and its effect on the left ventricle, but also [consider] the downstream effects on global cardiac function.”

Benoy Shah, MBBS, MD (Southampton General Hospital, England), speaking with TCTMD, touched on similar themes. “If you look at what’s happening with the whole of the heart and not just the aortic valve, you can get some quite interesting insights,” he observed.

The assertion that aortic valve disease needs to be detected earlier is a valid one, said Shah, but “I think we need to be careful about jumping to the conclusion that this means automatically we need to be intervening earlier” on the valve.

He pointed out that the classification system captures aspects apart from aortic stenosis. “There are so many other things that can affect those parameters,” he stressed, so it’s important to think beyond the AVR itself. “It’s absolutely crucial that in these patients that already have a pressure load on the heart from aortic stenosis, that we really manage their other risk factors as well.”

Perhaps eventually there will be a comprehensive framework that captures both the severity of aortic stenosis and the extent of cardiac damage, Shah suggested. “Can they, or should they, in some way be amalgamated?”

Philippe Pibarot, DVM, PhD (Laval University, Quebec, Canada), who presented the abstract today at EuroPCR, told attendees that there is room for refinement. Based on evidence from asymptomatic patients—here the cohort was exclusively symptomatic—the ideal timing for AVR seems to be between stage 1 and 2. But it’s clear, however, that “there are different types of stage 2, so I think we need to further refine this staging classification, maybe with blood biomarkers such as troponin and BNP,” he said, adding that cardiac magnetic resonance might also prove helpful in identifying responders versus nonresponders to AVR.

Just 15% Saw Improvement

For their study, the researchers pooled 1,974 patients who underwent AVR in the PARTNER 2 and 3 trials and who had complete transthoracic echocardiography (TTE) data for staging at baseline. Risk was inoperable/extreme for 17.3% of the cohort, intermediate for 54.3%, and low for 28.4%. Sixty percent were treated with TAVI and 40% with SAVR.

Patients’ extent of cardiac damage prior to their procedure varied:

• Stage 0: no damage (6.1%)
• Stage 1: LV damage (14.5%)
• Stage 2: left atrial or mitral valve damage (51.4%)
• Stage 3: pulmonary vasculature or tricuspid valve damage (20.9%)
• Stage 4: RV damage (7.1%)

Baseline damage was associated with mortality 2 years after AVR (HR 1.51 per higher stage; 95% CI 1.32-1.72), as well as the combined risk of mortality and heart failure (HF) hospitalization. Even after adjusting for baseline cardiac damage, the extent of cardiac damage at 1 year predicted both endpoints.

Risk at 2 Years by Baseline Cardiac Severity

At 1 year, 1,120 patients were alive and had paired TTE assessment from baseline and follow-up.

Cardiac damage remained unchanged for 60% of patients and worsened in 25% over the year since AVR. Just 15% saw an improvement. Of the patients in stage 1, for example, 40.9% progressed to higher stage and 7.2% died by 1 year. Of the patients who started out in stage 2, 24.7% saw worsening cardiac damage and 15.2% died.

These shifts in stage also were linked to 2-year mortality, such that patients whose damage improved saw a decrease in risk (adjusted HR 0.49) and those whose damage worsened saw an increase in risk (adjusted HR 1.95). Similar patterns were seen for the death/HF hospitalization composite.

Independent predictors of stage deterioration included hypertension (OR 1.73; 95% CI 1.01-2.96) and SAVR as the index procedure (OR 2.04; 95% CI 1.52-2.74).

Généreux said this is an argument for better blood pressure control. “Yes, you remove the aortic stenosis but you still have an increased afterload with hypertension,” he commented.

The link between progression and SAVR “is not surprising, since it is a more-invasive procedure,” he observed. Additionally, the paper notes, “SAVR is known to be associated with an increased rate of new-onset atrial fibrillation after AVR, increased risk of patient-prosthesis mismatch with reduced LV mass regression, and postoperative RV dysfunction related to cardiopulmonary bypass process or suboptimal RV protection during surgery.”

The Right Treatment at the Right Time

Ouzounian said it’s necessary to “dig into exactly why some patients improve and others don’t.” The analysis supports being “more aggressive at treating concomitant cardiac issues that may lead to poor prognosis, like mitral insufficiency or tricuspid insufficiency,” she commented.

Watchful waiting . . . only works if you’re actually watchful. Benoy Shah

This staging system should now be studied prospectively, added Ouzounian. Perhaps “we will learn that intervening in the asymptomatic stage, or even in the moderate stage, may be the best way to prevent the irreversible damage from happening.”

That information is in the works. EARLY TAVR finished enrollment 6 months ago, said Généreux, while PROGRESS recently began enrolling patients. Both trials are tracking cardiac damage.

Shah, regarding the current analysis, highlighted the cohort’s older age (mean 81 years) and comorbidity burden: nearly one-third had diabetes, 92% had hypertension, 55% had CAD, and half were in class III heart failure. It’s unclear how the staging system would translate in younger patients. Another question for younger patients is how earlier intervention might result in the need for repeat procedures, he added.

On the whole, prompt treatment for those who need it is clearly important, Shah said. Yet there are many challenges in terms of timing. “Watchful waiting” in patients who haven’t yet undergone AVR “only works if you’re actually watchful, if you’re doing it very regularly almost like a hawk. You’ve got to keep a really close eye on these patients. Absolute maximum follow-up should be 6 months. Sometimes you might need to see them every 3 or 4 months. And of course a lot of health systems don’t have the capacity to see people that frequently,” he said, adding that even after the decision is made to intervene, there can be further months-long delays before the procedure is done.

Note: Généreux is a faculty member of the Cardiovascular Research Foundation, the publisher of TCTMD.