Surgery for IE After TAVI No Better Than Antibiotics in High-Risk Patients

Among a group of high-risk patients who developed infective endocarditis (IE) after transcatheter aortic valve implantation, cardiac surgery failed to improve clinical outcomes when compared with antibiotic treatment alone. The registry findings, spanning a decade and half, capture even the earliest days of transcatheter procedures.

Just one in five patients with IE included in the international registry underwent cardiac surgery, but despite the aggressive treatment, in-hospital and 1-year mortality were not significantly improved with surgery compared with conservative medical management.

Senior investigator Josep Rodés-Cabau, MD, PhD (Quebec Heart & Lung Institute/Laval University, Canada), said that taking these high-risk patients to the operating room is not an easy decision for surgeons, given their significant comorbidities and IE-related complications.

“In this patient population, it’s difficult to apply general rules and treatment should involve a tailored, individualized approach,” Rodés-Cabau told TCTMD. “It should involve a specialized endocarditis team trying to decide what the optimal treatment is for each patient, especially considering that both treatment options seem to be associated with an equally poor outcome. The mortality in both groups remains very high.”

The results, he added, emphasize the “importance of prevention, prevention, prevention and early diagnosis” of IE.

In the end, you’re dealing with an extremely high-risk population, and on top of that you have a valve that is infected. Josep Rodés-Cabau

Gilbert Tang, MD (Mount Sinai Medical Center, New York, NY), who wasn’t involved in the study, said the take-home message is that you shouldn’t take such sick patients to surgery, because it’s not going to help. He noted that heart failure and stroke were common complications in this cohort of IE patients, affecting 42% and 10%, respectively. Also, more than a quarter of patients developed septic shock.

“Based on this registry, they are dealing with patients who are pretty sick,” Tang told TCTMD. In the earliest days of TAVI, a time captured in these data, only people at the highest risk for surgery or ineligible for surgery were treated with a transcatheter valve. “This puts the heart team into a bind when you’re presented with this situation. Should you try to operate? The patient might not make it out of the operating room or to 30 days. Also, if anyone has had a stroke, taking them to operating room is not a benign undertaking.”

Most of the patients who underwent surgery did so because they had no other alternative, he noted, adding that surgery in such circumstances is a “pretty dire situation.”

The study was published online February 21, 2022, in the Journal of the American College of Cardiology.   

IE Is Rare, but Its Outcomes Dire

The incidence of prosthetic valve endocarditis after TAVI ranges from 0.6% to 3.4% depending on the study, which is similar to IE rates after surgical aortic valve replacement. Symptoms can be variable, said Rodés-Cabau, and generally involve fever and a deterioration of the patient’s overall health. In older patients, though, the symptoms can be atypical, and in others the first sign something is amiss might be an IE-related complication, such as stroke. 

Targeted antibiotic treatment lasting approximately 6 weeks is recommended for the treatment of IE, but surgery is required in more-critical situations. For example, emergent surgery for IE is required in patients with acute severe aortic regurgitation (AR) or fistula obstruction that leads to pulmonary edema/shock. Additionally, urgent surgery is necessary for severe AR/obstruction with heart failure, new conduction abnormalities, and uncontrolled infection with an enlarging vegetation or the formation of abscess, fistula, or pseudoaneurysm. Embolization despite appropriate treatment, large vegetations, and fever or positive blood cultures lasting longer than one week without cause are also indications for surgery.

The study, which includes data from the Infectious Endocarditis After TAVI International Registry, involves 584 patients from 59 TAVI centers in North America, South America, and Europe enrolled with a definitive diagnosis of IE between 2005 and 2020.

To TCTMD, Rodés-Cabau noted that because the registry captures the very early TAVI era, the series included older patients who were ineligible or at very high risk for surgery. Overall, the median age of patients was 80.7 years, 43.2% had chronic renal failure, 13.2% had a previous stroke, and 22.6% had previously undergone heart surgery. Approximately 44% developed an infection in the healthcare setting.

Overall, 19% of patients were treated with cardiac surgery and antibiotics, and the rest were treated with antibiotics alone.

This puts the heart team into a bind when you’re presented with this situation. Should you try to operate? Gilbert Tang

“What we realized is that at least half of our study population would have had an indication for surgery, but only a minority got the operation,” said Rodés-Cabau. “The reasons are multifactorial, but it’s mainly related to the fact that many of these patients were already considered high risk for surgery, if not prohibitive risk. In the end, you’re dealing with an extremely high-risk population, and on top of that you have a valve that is infected.”

Those who underwent surgery were younger, had a higher body mass index, and were less likely to have chronic renal failure than those treated with antibiotics. The logistic EuroSCOREs of those treated with surgery/antibiotics and antibiotics alone were 14.7% and 11.5%, respectively. Significant predictors for performing cardiac surgery included TAVI device involvement, large vegetations (> 10 mm), periannular complications, and IE-related complications, including heart failure, other systemic embolization, and persistent bacteremia.

As for the surgery, which was performed a mean of 17.5 days from symptom onset, 52% of patients underwent isolated aortic valve replacement, 9.4% required aortic root replacement, 2.8% underwent isolated mitral valve replacement, and 17% had isolated device extraction. More than one in five patients had combined procedures.

The mean follow-up of patients who survived the hospitalization was 14.3 months. Crude in-hospital mortality in the entire cohort was 31.9%, with no significant differences between those treated surgically and those treated with antibiotics. Crude 1-year mortality in the entire cohort was 47.9%, and again there was no significant difference between surgery and antibiotics alone (47.1% vs 48.2%, respectively). Mortality was no different between the two treatment in patients with IE that involved and did not involve the valve bioprothesis.       

To control for treatment selection bias, the researchers calculated the probability of surgery for each patient based on propensity scoring and accounted for “immortal time bias” by adding cardiac surgery as a time-varying covariable into a fully adjusted risk model. In the adjusted analysis, cardiac surgery was not associated with reduced in-hospital mortality (HR 0.92; 95% CI 0.80 to 1.05) or 1-year mortality (HR 0.95; 95% CI 0.84 to 1.07).  

What About Lower-Risk Patients?

Tang, who coauthored a state-of-the-art review on IE after SAVR and TAVI, said it will be critical to learn how patients who aren’t as sick fare with surgery versus antibiotics. This would include patients identified early, such as those diagnosed before the onset of heart failure, stroke, or other embolic events. He added, however, that it can be difficult to identify infection on echocardiography and other imaging modalities given that “there’s so much hardware” with TAVI bioprostheses. For that reason, the condition is frequently diagnosed late and may be underdiagnosed in general.

“I think an important question to ask is what to do with the younger, lower-risk patients,” said Tang. Asked if they would fare as badly with surgery as in this cohort, Tang said: “My suspicion is probably not, especially if you diagnose them early.”

In an editorial, Joanne Chikwe, MD (Cedars-Sinai Medical Center, Los Angeles, CA), also emphasizes that the registry included a highly selected population and that these outcomes are unlikely to reflect outcomes of surgery or conservative treatment with antibiotics in lower-risk groups. It does, however, underscore the poor surgical outcomes of IE patients who underwent TAVI because they were poor candidates for SAVR.

It also underlines “the dismal outcomes associated with medical management of prosthetic valve endocarditis complicated by persistent bacteremia, large vegetations, or annular abscess,” writes Chikwe.

“If indeed more than 40% of these patients developed endocarditis due to healthcare-associated infections, a stronger case should probably be made for aggressive antibiotic prophylaxis and prevention strategies in high-risk patients after TAVR, particularly for patients requiring chronic treatment such dialysis or readmission to hospital,” she advises.