By Michael Crawford, MD, Editor

SYNOPSIS: An international registry study of left-sided valvular infective endocarditis patients revealed that large vegetations (> 10 mm) are associated with increased mortality at six months, but not if early surgery is performed.

SOURCES: Fosbøl EL, Park LP, Chu VH, et al. The association between vegetation size and surgical treatment on 6-month mortality in left-sided infective endocarditis. Eur Heart J 2019;40:2243-2251.

Habib G. How do we reduce embolic risk and mortality in infective endocarditis? Measure the size of the vegetation and operate early in patients with large vegetations. Eur Heart J 2019;40:2252-2254.

There is conflicting evidence on the benefits of early surgery for large vegetations in patients with left heart valve infective endocarditis (IE). Investigators from the international collaboration on endocarditis (ICE) tested the hypothesis that early surgery before finishing antibiotic therapy in IE patients with vegetations > 10 mm would result in a lower six-month mortality compared to not operating. ICE is a prospective, multinational registry of consecutive IE, cases collected from 34 centers in 18 countries, hospitalized between 2008 and 2012, with at least six months of follow-up. Patients with device-related IE were excluded. In patients with multiple IE episodes, only the first episode was included. Fosbøl et al used transesophageal echo to determine vegetation size. The authors used a propensity score model to account for other reasons for surgery.

Among 2,124 patients in the ICE registry, 1,006 had left-sided IE with vegetation size recorded; 58% of these patients had large vegetations (> 10 mm). Operative risk in both groups was similar. Embolic events were more common in patients with large vegetations (44% vs. 28%; P = 0.001) as was six-month mortality (25% vs. 19%; P = 0.001). After propensity adjustment, the association with higher mortality for patients with larger vegetations was seen only with medical management (HR, 1.86; 95% CI, 1.48-2.34), not surgical management (HR, 1.01; 95% CI, 0.69-1.49). Patients with large vegetations more often had Staphylococcus aureus IE (26% vs. 20%; P = 0.026).

The authors concluded that in patients with left-sided IE and vegetation size > 10 mm, increased six-month mortality was observed, but it was treatment-dependent in that undergoing surgery eliminated the higher mortality of a large vegetation.

COMMENTARY

Left heart valve IE is extremely challenging for many reasons, but seeing on echo the impending disaster of a large vegetation (especially if it is mobile) takes the cake. Early operation always is a tough sell to surgeons, even if other indications for surgery are present. Still, large vegetations are known to increase the risk of emboli and mortality. On the other hand, the risk of systemic emboli decreases rapidly after a few days of antibiotics and is rare after two weeks of therapy. Surgeons often find reasons to delay, even though one randomized, controlled trial of 76 patients has shown that early surgery for large vegetations decreases the risk of emboli, but not six-month mortality.¹

However, in the Fosbøl et al study, many patients crossed over to surgery later in their hospital course, which could have improved the outcomes for the initial medical therapy group. Thus, this registry study is of interest because the authors focused on the issue of mortality at six months. Fosbøl et al showed that early surgery, a median seven days after admission, decreases the embolic rate and mortality at six months compared to medical therapy, after adjusting for surgical selection criteria and estimated operative risk. These adjustments are important because there were considerable baseline differences between the surgery and medical treatment groups. Surgical patients were younger and presented with more complications such as heart failure, paravalvular complications, and persistent bacteremia.

Although informative, there were limitations to the Fosbøl et al study. It was a retrospective analysis of observational data from selected tertiary care centers. Surgery was performed at the discretion of the local physicians. There was no core echo lab to confirm vegetation size, and there were no data on vegetation mobility. Also, the authors only examined all-cause mortality. The U.S. guidelines give a IIb recommendation to consider early surgery if vegetation size is > 10 mm and it is mobile.² The ESC guidelines give a class I indication for surgery if a left-sided valve vegetation is > 10 mm and if one or more systemic emboli have occurred despite antibiotic therapy.³ A class IIa recommendation is a large vegetation with hemodynamic effects, such as severe stenosis or regurgitation (also for a very large vegetation [> 30 mm]). A 15-29 mm vegetation receives a class IIb rating. At a measurement of 10-15 mm, with no other indications, surgery would not be recommended by either guideline. If the results of this ICE registry study are adopted into the guidelines, they probably would recommend early surgery for left-sided IE with vegetation size > 10 mm, regardless of other characteristics or complications at level II. In addition, in practice a large vegetation plus other high-risk features would strengthen the recommendation for surgery. In an area with a paucity of data, this registry study adds important information.

REFERENCES

1. Kang DJ, Kim YJ, Kim SH, et al. Early surgery versus conventional treatment for infective endocarditis. N Engl J Med 2012;366:2466-2473.
2. Baumgartner H, Falk V, Bax JJ, et al. 2017 ESC/EACTS Guidelines for the management of valvular heart disease. Eur Heart J 2017;38:2739-2786.
3. Nishimura RA, Otto CM, Bonow BO, et al. 2017 AHA/ACC focused update of the 2014 AHA/ACC guideline for the management of patients with valvular heart disease: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol 2017;70:252-289.