Differing Advice for Infective Endocarditis Surgery Stems From Evidence Gaps

Strategies for surgery to treat left-sided infective endocarditis (IE) differ between the US and Europe, in large part because the evidence base is limited, according to a new review that compares guidelines from the two regions.

The paper, published recently in the European Heart Journal, “exposes areas of uncertainty and gaps in current evidence for the use of surgery in IE across different indications, particularly related to its timing and consideration of operative risk,” write co-authors Andrew Wang, MD (Duke University Medical Center, Durham, NC), and Emil L. Fosbøl, MD, PhD (University Hospital of Copenhagen, Rigshospitalet, Denmark).

The latest guidelines to mention the topic were two 2021 documents on the management of valvular heart disease as a whole: one from the American College of Cardiology and American Heart Association and the other a joint publication of the European Society of Cardiology and the European Association for Cardio-Thoracic Surgery. Notably, Wang and Fosbøl say, these most-recent European recommendations are the same as those in an IE-specific document released back in 2015.

Wang told TCTMD that, with the release of the latest US guidelines, there was a “good opportunity to compare” the different documents’ advice on IE. What their review offers is a thorough look at the evidence base on the main indications for surgery in IE, as well as an exploration of where the US and Europe do—and don’t—diverge.

Anytime we think about doing something inside the heart, [IE is] a known complication long term. Andrew Wang

Infective endocarditis, said Wang, is “highly relevant to the patients that we take care of,” whether that’s through aortic or mitral valve interventions, pacemakers, left ventricular assist devices, or other cardiac procedures. “Anytime we think about doing something inside the heart, that’s a known complication long term,” he noted. “The main question outside of diagnosing endocarditis that a cardiologist is going to be involved with is deciding: does this patient have a need to go to surgery?”

A Resource for Clinicians

Bernard Prendergast, MD (St Thomas’ Hospital, London, England), commenting for TCTMD, agreed: “It’s always useful to compare guidelines from a number of perspectives. One is that the European and US guidelines are often a little out of . . . synchrony with each other in terms of timing, so it’s often a useful opportunity to evaluate the evolution of evidence and the evolution of practice. Secondly, it’s often quite fascinating how different groups can look at the same evidence base and draw slightly different conclusions.”

For IE, and for the valve guidelines more generally, “it’s heartening that for the most part there’s concordance and the overall messages are the same,” he said.

John P. Erwin III, MD (NorthShore University HealthSystem, Chicago, IL), who co-authored the 2021 US valve guidelines, described the review as a “good article” for its description of IE management. Cardiologists, he told TCTMD, “now have a resource that they can go to: all of the studies are there, all of the data that we do have are there, and you have to learn to apply those to the patient that’s in front of you.”

As for the US versus European recommendations, Erwin said it just comes down to “how people parse the information.” The ACC guideline-writing committees “have really tried very hard to cut out as many of the ‘expert consensus’ statements’ [as possible],” he explained. “The ESC has not done that quite as much.” Erwin pointed out that within the review itself there’s language such as “we favor,” denoting when Wang and Fosbøl offer their own interpretation.

All agreed there are more similarities than differences.

“Both ESC and ACC/AHA guidelines consider heart failure, uncontrolled infection, and embolic risk as surgical indications,” the co-authors note. The dissimilarities relate to timing of surgery, what’s considered a “large vegetation” (> 30 mm in Europe vs > 10 mm in the US), and the dual considerations of vegetation size and emboli as indications for surgery.

Most salient among these is timing, said Wang. Whereas the European recommendations differentiate between “emergency” (< 24 hours) and “urgent” (within a few days), as well as “elective,” in the United States the only specified time frame is “early” (during the initial hospital stay and before the completion of an antibiotic regimen).

“The American guideline is a very broad definition,” he observed, adding, “I think if you told a patient you’re going to have early surgery, they would say, ‘Oh, that means within the next day or so, right?’” With the current phrasing, though, an early surgery could occur 4 weeks later, Wang said.

The reason for this particular gap between the guidelines is that the US document “recognizes the limitations of the data,” which don’t point to specific timing, he explained, whereas the European document relies more on expert consensus based on what’s known about the reason for surgery.

Where we don’t have definitive black-and-white evidence, then it really does need to be the best people from multidisciplinary approaches coming together to make the right decision for the individual patient. John P. Erwin III

For Prendergast, the time frame set by the US guidelines is “a little bit vague, if I’m absolutely honest, because many patients with endocarditis are on antibiotics for 6 weeks,” he said. “So distinguishing between greater or less than 6 weeks is a fairly blunt instrument, whereas if you are saying, ‘This patient needs an operation and they need it tomorrow,’ that’s a fairly robust instruction for a surgeon.” Without a firm deadline, the risk is that surgery could be deferred too long, in part because a particular surgeon or an operating room may not be available until a later date.

“I think the more-pressing categories provided by the ESC guidelines do challenge systems of care . . . and [this] encourages teams of surgeons to think about the way they work in a different way,” said Prendergast. “And I think that’s good.”

A remedy for the “gray areas,” said Erwin, is the heart team, a concept purposefully emphasized in the US guidelines. “Where we don’t have definitive black-and-white evidence, then it really does need to be the best people from multidisciplinary approaches coming together to make the right decision for the individual patient.”

Wang and Fosbøl, too, emphasize the need for cooperation, noting: “Both the American and European guidelines recommend that all decisions regarding the indication and timing of surgical intervention for IE should be made by a multidisciplinary endocarditis team of infectious disease, cardiology, and cardiac surgery specialists [with] understanding of IE treatment options and their appropriate and optimal use in the individual case, not simply a heart team of subspecialists.”

Room for Interpretation

A key argument in the review is that an incomplete evidence base leaves room for interpretation. Most of the data stem from retrospective, observational studies.

“Endocarditis is ones of the areas where the level of evidence is so weak that it leaves more room for expert consensus,” said Wang. “When you’re talking about revascularization, bypass surgery, PCI guidelines, there’s thousands of randomized patients [and] it’s hard to say the data doesn’t speak for itself. Here, it’s observational and there’s a lot of local expertise.”

There is no right or wrong answer about how to interpret the available evidence, he stressed. “But there are differences, and people should realize timing in and of itself is a tough decision.”

Endocarditis is such a heterogeneous condition. It’s not like putting a stent in the right coronary artery or putting a TAVI in a bicuspid valve. Bernard Prendergast

Describing what’s known, Prendergast observed that existing registries are done mainly at experienced centers and may not be generalizable to practice patterns elsewhere. “To my knowledge, there are no countries that have mandatory registries of endocarditis, so we don’t accumulate this information at a national or international level,” he said.

Prendergast predicted that RCTs of surgery will be “extremely challenging” to conduct in this space, “because endocarditis is such a heterogeneous condition. It’s not like putting a stent in the right coronary artery or putting a TAVI in a bicuspid valve. . . . There’s variation of patients, there’s variation of the underlying disease, there’s variation of the organism, and there is variation of the comorbidities, so designing a nice, clean randomized controlled trial is almost impossible.”

European guidelines for endocarditis are now being updated and will be published in 2023.

EASE, perhaps the best-known trial of IE, was published in the New England Journal of Medicine in 2021; with 76 participants, it looked at early surgery (within 48 hours) versus conventional treatment (surgery during hospitalization or follow-up). Now, the ASTERIx trial, led by Fosbøl, is in the process of recruiting nearly 500 participants to compare antibiotics with versus without surgery, and there’s also POET, examining partial oral versus parenteral antibiotics. Both are being conducted in Denmark.

In the United Kingdom, they’re working to create audit standards for IE care, said Prendergast. “You can assess compliance with guideline-based practice and you can then use that to generate quality metrics regarding standards of care and compare one institution with another, or you can produce national rankings.”