Infective Endocarditis Rare After AVR, but Often a Killer When It Occurs

Infective endocarditis (IE) is a rare but often deadly complication for patients whose aortic stenosis is treated with a transcatheter heart valve or with surgery, according to a new analysis of several randomized trials and an observational registry.

When compared with patients who received a supra-annular, self-expanding valve (CoreValve, Evolut R, and Evolut PRO; Medtronic), the risk of IE was higher among patients who underwent surgical aortic valve replacement, although investigators say the difference between the two procedures should be interpreted cautiously.

“As opposed to highlighting the difference in cumulative incidence between TAVR and SAVR observed in our study population, I would rather emphasize that our findings indicate that IE rates after TAVR using the self-expanding CoreValve or Evolut platform are low,” lead investigator Jonas Lanz, MD (Bern University Hospital, Switzerland), told TCTMD in an email. “Considering the large stent frame of the platform and in view of expansion of TAVR to younger and low-risk patients, this is a particularly reassuring finding.”

In previous studies, neither crude nor adjusted incidence rates suggest significantly different rates of IE between the two procedures, said Lanz. While their study was based on data from randomized trials with clinical event adjudication committees, the diagnosis of endocarditis is “complex” and misclassification possible because the modified Duke criteria used to diagnosis IE is limited, he added.

“Endocarditis remains a rare, but ongoing, persistent problem for patients undergoing aortic valve replacement with TAVR and SAVR,” Thomas Cahill, MBBS, DPhil (Columbia University Irving Medical Center, New York, NY), who wasn’t involved in the study, told TCTMD. “The risk continues out after the long term, well after the procedure, and we clearly need as a field to be focusing on identifying evidence-based strategies for minimizing and reducing that risk.”

Cahill, who has investigated the risk of IE after TAVI in the United Kingdom, also urged caution with respect to the comparative risks of that complication after TAVI and SAVR, but said the new analysis does hint at a difference between the two procedures. “Now, it’s statistically significant, but it requires validation and reproduction,” he said. “Still, even when the populations are balanced between the arms as they were in this analysis, it suggests there may be a difference in risk associated with TAVI versus SAVR. We need to see if it holds up, and why it might be, but it’ll be of interest going forward.” 

Half of Cases Occur Beyond 1 Year

The study, which was published September 29, 2021, in the Journal of the American Heart Association, consisted of patients treated either with TAVI or SAVR as part of the CoreValve High-Risk, SURTAVI (intermediate risk), and Evolut Low-Risk clinical trials, as well as patients enrolled in the SURTAVI continued access study. Among 2,249 patients implanted with a TAVI device, there were 12 cases of IE (0.5%) after a median follow-up of 2.15 years. For the 1,828 patients treated surgically, IE was reported in 21 patients (1.1%) during 2.17 years of follow-up. Patients with endocarditis had more NYHA class III/IV heart failure symptoms at baseline and were more likely to have diabetes.

The incidence of IE was 3.74 per 1,000 person-years of follow-up in patients treated with TAVI and SAVR. Separately, the incidence per 1,000 person-years was 2.47 for those treated with TAVI and 5.28 for those treated with surgery. The overall cumulative incidence of IE at 5 years was 1.01% for those treated with TAVI and 1.58% with surgery, both of which accounted for the competing risks of death (P = 0.047). Overall, half of the IE cases occurred in the first year and the other half beyond 365 days. The most frequent cause of IE was Streptococcus (33.3%) and Enterococcus (30.3%) species, and there was no notable difference between the TAVI and SAVR groups in terms of causative microorganisms. 

While endocarditis occurs infrequently, there are “devastating consequences” when it does happen, said Lanz. Overall, 42.3% of patients who developed IE had died at 1 year. In the TAVR cohort, the risk of death at 1 year was 27.3% among those who developed IE. In the surgical group, it was 51.8%. Mortality rates continue to be high despite all the medical progress of the past decades, said Lanz.

“Though there are clearly some factors predisposing patients to endocarditis, such as valvular heart disease, previous IE, prosthetic heart valves, certain congenital heart malformations, and intravenous drug use, the risk of endocarditis hardly ever affects the mode of aortic valve replacement in clinical practice,” said Lanz. “This is supported by our study and the previous evidence which do not suggest clinically meaningful differences in the incidence of IE comparing TAVR and SAVR. However, continued evaluation of the risk of IE associated with different modes of valve replacement and devices is required, particularly as TAVR is moving more and more towards low risk and younger patients.”

Cahill also highlighted the enormous risk of death in patients with IE, which is consistent across all studies published to date.

“It suggests we still don’t have good treatment options for patients who present with infective endocarditis,” he said. “One interesting aspect of this study is that the dominant organism identified is Streptococcus, which often originates in the mouth and teeth. There’s been a big focus on whether patients should have antibiotic prophylaxis after aortic valve replacement when they’re undergoing dental work but there’s still a lot of debate about the efficacy. It comes back to that we just don’t have good ways of predicting, preventing, and treating infective endocarditis.”

Focusing research, energy, and funding will be key “if we’re going to have an impact on outcomes for patients who develop this complication,” added Cahill.

Abscess Formation With Surgery

Of note, abscess formation was more frequently reported in patients treated surgically—47.6% vs 8.3% with TAVI—and while this might be related to differences in the procedures, such as resection of the aortic valve or deeper wound trauma with SAVR, the finding should also be considered exploratory as it could be due to chance or detection, said Lanz.

To TCTMD, Lanz said their overall findings are in line with other studies, with similar incidence and mortality rates, as well as similar causative microorganisms. The yearly incidence of IE—0.4% overall—in the pooled randomized, controlled data was very similar to that seen in the pooled PARTNER data with the balloon-expandable Sapien, Sapien XT, and S3 (Edwards Lifesciences) devices. In the PARTNER analysis, there was no significant difference in incidence of IE difference between TAVI and SAVR.

Regarding prevention of early periprocedural endocarditis, “sterility during valve preparation and of the procedural environment is paramount,” said Lanz. “Antibiotic prophylaxis is recommended in patients with predisposing conditions before selected procedures associated with a high risk of relevant transitory bacteremia.”