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Infective endocarditis patients do substantially better when sent for surgery early rather than waiting to see if antibiotics will be effective, according to a small clinical trial.

Sending patients with infected native valves to surgery within 48 hours of definitive diagnosis cut the risk of in-hospital death or embolic events, like heart attack or stroke, by 90% compared with the conventional antibiotics-first approach, Duk-Hyun Kang, MD, PhD, of Asan Medical Center in Seoul, South Korea, and colleagues found.

The composite 6-week rate of those events reached only 3% in the early surgery group compared with 23% in the delayed surgery group (one of 37 versus nine of 39, P=0.03), the investigators reported in the June 28 issue of the New England Journal of Medicine.

The advantage was driven by a reduction in systemic embolism rather than all-cause mortality, they wrote.

Guidelines recommend urgent surgery for infective endocarditis patients with congestive heart failure brought on by valvular regurgitation due to the infection.

Severe valve dysfunction without heart failure, though, has been a gray zone for surgical timing, according to an accompanying editorial.

"In this context, the implication of this study for early surgery is profound and raises the bar for the treatment of patients who do not have urgent indications but do have valve dysfunction and vegetations," wrote Steven M. Gordon, MD, and Gösta B. Pettersson, MD, PhD, both of the Cleveland Clinic.

They called the results convincing, agreeing that the prospective, albeit small, two-center study should change practice as predicted by cardiac surgeons when the results were first released.

A striking finding was that even in the conventional treatment group observed for resolution on antibiotics, few patients ultimately escaped need for surgery, the editorialists noted. Fully 77% ultimately required valve surgery for infective endocarditis (30 of 39), most during the initial hospitalization.

Of those discharged without surgery, 55% (six of 11) had symptoms caused by the regurgitant valves. Two of them subsequently got surgery, while four declined surgery or were no longer surgical candidates.

Of the other five without symptoms or surgery, one died suddenly soon after completing antibiotics and one had recurrent heart valve infection that required urgent surgery.

"This study underscores the points that infective endocarditis is a dangerous condition and that the benefits of timely surgical intervention in patients with large vegetations and severe valvular dysfunction, even if they do not have congestive heart failure, outweigh the additional risk of surgery in patients with active infection," Gordon and Pettersson argued.

The open-label Early Surgery versus Conventional Treatment for Infective Endocarditis (EASE) trial included patients with left-sided infective endocarditis and severe mitral or aortic valve disease, as well as high risk of embolization due to vegetations with a diameter over 10 mm. Patients were randomized to early surgery or to conventional treatment with antibiotics.

Patients with clear indications for urgent surgery, like moderate-to-severe congestive heart failure or destructive penetrating lesions, were excluded, as were cases complicated by heart block or annular or aortic abscess or fungal endocarditis.

Antibiotic regimens, duration of use, and control of the underlying infection didn't differ between groups.

Six-month outcomes showed no difference between groups in terms of all-cause mortality (3% early versus 5% conventional, hazard ratio 0.51, 95% CI, 0.05 to 5.66).

But there was a persistent advantage to early surgery in terms of the composite of death from any cause, embolic events, recurrence of infective endocarditis, or repeat hospitalization due to the development of congestive heart failure (3% versus 28%, HR 0.08, 95% CI 0.01 to 0.65, P=0.02).

The researchers cautioned that their findings wouldn't generalize to infective endocarditis involving a prosthetic heart valve or aortic abscess.

Also, the inclusion criteria skewed the proportion of cases toward viridans streptococci as the predominant cause of infection, which may influence the risk-benefit ratio of surgical timing, they noted.

"The results of our study may not be applicable to low-volume medical centers or to patients with high operative risk," the group added.

From the American Heart Association: