Long-term impact of persistent vegetations at 6 month followup after treatment of infective endocarditis: a substudy of the Partial Oral vs Intravenous Antibiotic Treatment of Endocarditis (POET) tria
Authors: Hjulmand J , Pries-Heje M , Try Lenz I , Carter-Storch R , Gill S , Bruun N E , Povlsen J A , Christiansen U , Helweg-Larsen J , Fosboel E , Toender N , Moser C , Iversen K , Ihlemann N , Bundgaard H 
Published: October 2022

Abstract

Background
Our knowledge of changes in vegetation size throughout the course of infective endocarditis (IE) and the impact of persistent vegetations on mortality or embolization after completed antibiotic treatment is sparse. No study has previously investigated the prevalence or clinical impact of persistent vegetations on transthoracic echocardiography (TTE) at 6-months follow-up after ended IE treatment.

Purpose
To investigate the association between persistent vegetations at the 6-months TTE after treatment for IE and long-term prognosis as assessed in the POET trial.

Methods
The POET trial was a nationwide, multicenter RCT, randomizing 400 patients to either partial oral or intravenous (IV) antibiotic treatment of left-sided IE, after initial stabilization of infection using conventional IV therapy.
A persistent vegetation was defined as a vegetation seen on 6-months follow-up TTE (4–7 months) after ended antibiotic treatment for IE. In the POET trial, primary outcome was defined as 1) all-cause mortality, 2) unplanned cardiac surgery, 3) embolic events or 4) relapse of bacteremia, in the 5-year follow-up period. Patients without TTE due to death or lack of available TTE were excluded.

Results
Out of 400 patients, 20 were excluded due to death during 6-months follow-up, and 201 were excluded due to unavailable TTE, leaving 179 TTEs for analysis.
At 6-months follow-up, a persistent vegetation was seen in 30 patients (16.7%, 21 males (70%), mean age 69.6 years (SD 7.7)) (Table 1). Seventeen patients (56.7%) had a persistent vegetation on the aortic valve and 13 patients (43.3%) on the mitral valve. More patients without a persistent vegetation had undergone initial surgical treatment of IE than those with a vegetation (57.7 vs 23.3%, p=0.001). In all surgically treated patients with persistent vegetation at 6-months follow-up, the vegetation was found on another valve than the operated valve.
The composite primary outcome from 6-months follow-up and until 5-year follow-up occurred in 8 patients (26.7%) with a persistent vegetation, compared to 38 patients (25.5%) (p=1.00) without. (Table 2) In patients randomized for peroral treatment, no significant difference in prevalence of persistent vegetation was found (15 patients (50%) with persistent vegetations vs. 74 patients (49.7%) without, p=1.00).

Conclusion
The occurrence of persistent vegetations at 6 months follow-up was 16.7%. There was no association between persistent vegetations at 6-months follow-up and the occurrence of the primary outcome after 5 years follow-up, suggesting that the risk associated with residual vegetations after end of antibiotic treatment is negligible after 6-months.

Funding Acknowledgement
Type of funding sources: Foundation. Main funding source(s): The Danish Heart Foundation