TAVR and Infective Endocarditis—Two Studies Address a Shifting Landscape

Infective endocarditis (IE) is rare after TAVR—and has been decreasing in recent years—but it’s linked to high mortality, Medicare data confirm. Although fewer than 1% of patients developed IE post-TAVR, nearly half of those who did died within a year.

Amgad Mentias, MD (University of Iowa Carver College of Medicine, Iowa City, IA), the paper’s lead author, told TCTMD that their study is consistent with IE data from PARTNER I and II but reproduces these same patterns in real-world use. Other observational reports on the topic have come from Switzerland, Finland, and Sweden.

One theme to emerge is the complexity of addressing IE when it occurs after TAVR. “I think it is important to recognize that TAVR [patients] are inherently a challenging population, especially when they develop endocarditis,” Mentias said. Diagnosis can be difficult, and treatment requires both imaging and surgical expertise.

Bernard Prendergast, MD (St Thomas' Hospital, London, England), commenting on the paper for TCTMD, said it contributes “to a quite rapidly growing body of literature about where we stand with infective endocarditis after TAVR. . . . what we have now is a collection of large series from around the world—different continents, different countries—with large numbers of TAVI recipients and reporting the incidence of endocarditis. I think the messages are all pretty consistent, and that’s encouraging and reassuring in many ways.”

Most notably, IE incidence appears similar for transcatheter and surgical aortic valve replacement, he said. While there are no direct comparisons for TAVR versus SAVR yet in this regard, data on contemporary cohorts are forthcoming from the United Kingdom, said Prendergast.

Published online recently in JACC: Cardiovascular Interventions, the study is one of two in the same issue to tackle the relationship between TAVR and IE. The other, admittedly “controversial” paper, according to its senior author, describes the use of TAVR as a remedy to IE in native or preexisting prosthetic valves when surgical management isn’t feasible.

“If we’re going to improve the outcomes of TAVI endocarditis, we need to be more aggressive with our interventional treatments. Currently, the standard of care would be [surgery],” Prendergast said, highlighting the fact that many patients receive medical therapy alone. Just 3.8% of patients in the Medicare data set underwent surgical management for their IE and 0.4% had repeat TAVR.

As the field as a whole moves into younger and lower-risk patients, the situation will continue to evolve.

Christian Spaulding, MD (European Hospital Georges Pompidou, Paris, France), urges in an accompanying editorial that, amid these changes, the field must be vigilant: “In the era of ‘minimally invasive’ TAVR performed in low-risk patients, IE prevention must not be put on the back burner.” When it comes to treatment, he said, “both papers help to answer a burning question: Is there a TAVR indication for severe residual aortic lesions after IE?” Registries such as these can help guide care in the absence of RCTs, Spaulding concludes.

IE After TAVR

Mentias and colleagues reviewed data on 134,717 Medicare patients who underwent TAVR between 2012 and 2017, of whom 1,868 subsequently developed IE. Although the overall incidence was 0.87% per year, nearly two-thirds of infections occurred within the first year after TAVR.

The most-common organisms responsible were Staphylococcus (22.0%), Streptococcus (20.0%), and Enterococcus (15.5%). Predictors of IE included younger age at the time of TAVR, male sex, prior endocarditis, end-stage renal disease, repeat TAVR procedures, liver and lung disease, and post-TAVR acute kidney injury (AKI).

Mortality was 18.5% at 30 days and 45.6% at 1 year. When accounting for comorbidities and procedural complications, IE post-TAVR tripled the risk of mortality from 16.2 to 44.9 deaths per 100 person-years (adjusted HR 2.94; 95% CI 2.77-3.12). Independent predictors of higher mortality after IE included end-stage renal disease, cardiogenic shock, ischemic stroke, intracerebral hemorrhage, AKI, and blood transfusion as well as staphylococcal and fungal endocarditis versus other organisms.

Over the 6-year study, there was a significant decrease in the crude incidence of IE. “This is most probably due to the expansion of TAVR to lower-risk patients with a lower burden of comorbidities, as well as the advances in prosthesis design and delivery systems reducing the incidence of paravalvular leak and procedural complications, which has shown to be linked to an increased risk of endocarditis,” the investigators suggest.

What Can Be Done

Some risk factors for IE are patient-related and aren’t modifiable, but there are some procedure-related factors that operators can address to minimize risk, Mentias said, such as acute kidney injury, need for blood transfusion due to bleeding, and severe paravalvular regurgitation after the TAVR device has been deployed.

“I think operators should aim to reduce as much as possible these postprocedural complications—by reducing the amount of contrast that they use, for instance, by using lower-profile delivery systems and applying best practices in getting vascular access to try to reduce vascular complications and subsequent bleeding, and also avoiding paravalvular regurgitation by proper positioning during deployment of the valve,” Mentias advised. “All of these factors would reduce the incidence more and more.”

Prendergast said, “there needs there to be a respect for the sterility of the procedure,” especially when it comes to valve prep and groin hygiene at the time of puncture. Clinicians also “need to educate our patients of this risk and the measures that they need to take to reduce that risk—so looking after their skin, looking after their teeth, and avoiding unnecessary medical instrumentation,” he suggested.

For Mentias, the fact that a large proportion of patients had microbial organisms consistent with nosocomial infection also highlights the need for precautions when TAVR patients are admitted to the hospital for reasons unrelated to their valve. Prendergast observed that, if periprocedural antibiotics are used during TAVR to prevent IE, they should target the most common culprits.

Mentias cited several research areas as worthy next steps, such as the role of prophylactic antibiotics before invasive procedures in patients who’ve previously had TAVR. Another is the question of how to best manage IE when it does develop post-TAVR, “to try to mitigate this high mortality that we and other studies have found,” he said.

“In our study, actually a very small proportion of the patients underwent any surgical management, and this is understandable due to the high-risk nature of these patients who get TAVR to start with,” added Mentias. He described surgical management as the “cornerstone” of treatment for IE, even more so in native-valve and SAVR-related IE. For TAVR patients, the role of surgical IE management is less clear.

TAVR as a Remedy

Even more murky, though, is TAVR’s potential as a remedy for IE that has healed but left residual damage in the form of a lesion—this is where the second JACC: Cardiovascular Interventions-published paper comes in.

Ignacio J. Amat-Santos, MD, PhD (Hospital Clínico Universitario, Valladolid, Spain), said “an infection of a native or a prosthetic valve is a contraindication for TAVR, or any new prosthetic device, before operating and debriding/cleaning the infection.” But he and others have encountered some IE cases for which surgical management wasn’t feasible and so they decided to try a new tactic.

“What we found is that with [strict] selection criteria, the use of TAVR was quite successful, more than what we expected,” he told TCTMD, noting that these procedures are done in patients who only require valve replacement (rather than multiple procedures) and when there is no longer any active infection.

Although they were quite surprised at how low mortality was in their study, given the riskiness of IE, Amat-Santos stressed that outcomes after TAVR for this difficult condition don’t match up with those of standard TAVR. Like Mentias, he said imaging skills are crucial when planning the procedure and sizing the TAVR device.

Led by Sandra Santos-Martínez, MD (Hospital Clínico Universitario), the researchers retrospectively gathered data on 2,920 TAVR patients treated at 10 centers in Europe and Canada between 2015 and 2018. In all, 54 (1.8%) had been diagnosed with possible or definite IE a mean time of 90 days (median 62) before their TAVR procedure.

The patients with prior IE had a higher prevalence of diabetes, CAD, chronic obstructive pulmonary disease, prior open-chest surgery, and frailty than the other TAVR patients; also, their peak gradients tended to be lower and their aortic valve area larger. Half had previously undergone SAVR and half had native aortic valves. Their median STS-PROM score was 11.8% and median logistic EuroSCORE was 21.2%.

The researchers then matched 46 of the prior-IE patients with 46 who were being treated for degenerative aortic stenosis. There was no significant difference between the two groups for in-hospital mortality (5.6% vs 5.0%) or 1-year mortality (11.1% vs 10.0%). Yet, the IE group did have much higher rate of grade III-IV aortic regurgitation at 1 year (27.9% vs 10%) and this factor was independently associated with higher mortality. There was one case of IE relapse, 10 of the IE patients (18.5%) had sepsis, and 43% were readmitted for heart failure.

Amat-Santos said he understands why it’s counterintuitive to treat IE with a therapy also known to cause it. But he emphasized that TAVR in this case is done when patients have no alternatives other than medical therapy, which carries high mortality.

“Someone might say that we are forcing the indication of TAVR,” he allowed. But if centers are doing this, their results should be reported, Amat-Santos said. “This was the aim of this manuscript. And the outcomes were not bad, which is the main conclusion for me.”

Referring to Twitter debates sparked by this study, he emphasized: “The first thing for us has to be the patient, not the professionals—if the patient needs a solution, we have to find the best solution and we have to register what we’re doing, and we have to report it.”

28% of patients developed significant AR and 43% required readmisión for CHF. Would you say that TAVI is safe for patients with endocarditis related aortic vale disease? 👇https://t.co/OMoJHlIXFQ

— Rafa Sádaba (@rafasadaba) September 8, 2020

Very few. But this research shows that is exists. One example from the series: Strepto, healed after antibiotics but leaflet perforation. Patent LIMA with prior mediastinitis. Yes... you can operate but high risk. https://t.co/yp2YaywIod

— Ignacio J. Amat (@ignamatsant) September 8, 2020

Prendergast agreed that the study shows TAVR in “healed endocarditis . . . is safe and feasible in expert hands.”

However, “there are some important questions about the longer-term outcomes with more residual aortic regurgitation, high level of symptoms, need for hospitalization, and indeed recurrent sepsis in nearly 20% of the cohort. So I think it’s an attractive option when surgery isn’t possible as a treatment for healed endocarditis,” he said. “But I don’t think it’s a panacea, and it’s certainly not a replacement for surgery when that is an option.”

As the field shifts there will be changes in who is a candidate for what, with consequences for future interventions, Prendergast observed. In the early days of TAVR, the treatment was reserved for people with severe, symptomatic aortic stenosis who couldn’t undergo SAVR, creating a “paradox,” he noted. “At time point one you’ve declared that the patient isn’t suitable for an operation, therefore they should have a TAVI. And then when they develop endocarditis a year later you say, well, can they have an operation now? Which is a much higher-risk operation because it’s for an infection and the patient’s 1 year older.”

Now, as TAVR moves into less-risky territory where patients would generally be better able to tolerate a more aggressive intervention to treat IE, “there will be some . . . whose condition is not suitable for surgery to address their hemodynamic problem,” he said. “They might have become a lot sicker since their TAVI. They might have multiorgan failure following their healed endocarditis. Other conditions may have come along that alter the clinical balance. I think these patients do exist. They will particularly be encountered at high-volume TAVI centers.”

The complexity of decisions reemphasize the need for a heart team with multidisciplinary input, Prendergast stressed.