Surgery Ups Survival in Infective Endocarditis With HF

November 28, 2011

November 24, 2011 (Chicago, Illinois) — Around the world, surgery decreased in-hospital mortality by one-fourth and one-year mortality by more than half compared with medical therapy in patients with infective endocarditis and heart failure, new research has found. The cohort study, which included over 4000 patients, probably represents the largest number of people with infective endocarditis ever prospectively followed as a group, the authors say [1].

Yet, according to an analysis from the International Collaboration on Endocarditis-Prospective Cohort Study, valve-replacement surgery is performed in less than two-thirds of such endocarditis cases with heart failure, note the authors, led by Dr Todd Kiefer (Duke University Medical Center, Durham, NC) in the November 23/30 issue of the Journal of the American Medical Association.

Other independent predictors of in-hospital and one-year mortality included older age, diabetes, and a history of stroke; infection with Staphylococcus aureus or fungi also raised both mortality risks, while other types of infection did not. Of note, heart-failure severity was also a mortality predictor, but surgery conferred a significant benefit whether NYHA status was 3-4 or 1-2.

According to Dr Andrew Wang (Duke University Medical Center), that was one of the trial's surprises: "the benefit of surgery on longer-term outcome, even in patients who had relatively mild heart failure." Heart failure, he told heartwire , "is one of the strongest indications for surgery in this disease. And although the rate of surgery was really higher in this group than in any other endocarditis [with HF] study--most showed the rate of surgery somewhere between 40% and 50%, and the rate here was 62%--I think seeing the benefit across the whole spectrum of heart failure makes you wonder why it isn't higher, and what can we do to make that rate higher."

The study included 4075 patients with confirmed native- or prosthetic-valve infective endocarditis and known HF status enrolled at 61 centers in 28 countries from 2000 through 2006. Of those patients, 1359 (33.4%) had heart failure, two-thirds of whom had NYHA functional status 3 or 4.

Although usual-care options varied at the study sites, all had access to cardiac surgery, Wang noted.

Not surprisingly, in-hospital mortality in infective endocarditis rose significantly with the presence of heart failure, with an odds ratio (OR) of 2.80 (95% CI 2.38–3.29) vs no heart failure. However, surgery during that hospitalization cut the risk by a third, with an OR of 0.66 (95% CI 0.56–0.77) vs medical therapy alone. Both risk reductions were significant at p<0.001. The effect was much more pronounced in NYHA 3-4 patients, but remained significant in those who were less symptomatic.

In-Hospital Mortality With Surgery vs No Surgery During Index Hospitalization, by NYHA Class (Total Rate 29.7%)

Heart failure severity Surgery, % No surgery, % p
NYHA class 1-2 7.9 15.0 0.03
NYHA class 3-4 23.4 54.5 <0.001
All heart failure 20.6 44.8 <0.001

Across the entire cohort, mortality at one year was 29.1% in those who underwent surgery vs 58.4% in those who received medical therapy alone (p<0.001), according to the group. In an analysis adjusted for surgery propensity, significant predictors of death within a year included increased age, diabetes, infection by S aureus or fungi (but not infection by Viridans group streptococcus or Streptococcus bovis), NYHA class 3-4 heart failure, stroke, and paravalvular complications.

Hazard Ratio (HR) for One-Year Mortality by Selected Subgroups Across Entire Cohort

Subgroup HR (95% CI)
Surgery, yes vs no 0.44 (0.34–0.56)
NYHA class 3-4, yes vs no 3.03 (2.45–3.80)
Diabetes, yes vs no 1.34 (1.14–1.57)
Age vs <45 y, y  
46–60 1.44 (1.13–1.84)
61–70 1.62 (1.26–2.09)
>70 2.40 (1.92–3.02)

Some of the variability in outcomes across the broadly international trial had to do with differences in criteria for selecting patients for surgery. The report notes other factors beyond heart failure that seemed to raise the likelihood, "including severity of heart failure, younger age, paravalvular complication, and transfer from another hospital." They suggest, among other things, "that surgery was performed in patients with the most serious complications of infective endocarditis . . . who had acceptable operative risk."

Also, according to Wang, "one of the next big questions is, if a patient has a reason for surgery, when is the best time for it?" He pointed to the recently reported but small EASE study, covered by heartwire , that showed a significant reduction in clinically significant embolic events with surgery performed within 48 hours.

Still, "the true decision-making as to why a patient has surgery, why at a certain time in the course of a long disease, and why some who have reasons for surgery don't have surgery, still need further investigation, and that’s the objective of the next iteration of this collaboration."

The study was partly supported by a National Institutes of Health grant to Kiefer, who had no other disclosures. Wang disclosed receiving grants or having grants pending from Edwards Lifesciences, Abbott Vascular, and Gilead Sciences; payment for lectures or otherwise serving on speakers bureaus from American Physician; payment for development of educational materials from the American Board of Internal Medicine and American College of Cardiology Foundation; and "serving as a defense reviewer (no expert testimony) for a legal case related to endocarditis." Disclosures for the other authors are included in the report.