By Michael Crawford, MD

Professor of Medicine, Associate Chief for Education, Division of Cardiology, University of California, San Francisco

Dr. Crawford reports no financial relationships relevant to this field of study.

SYNOPSIS: There are patients with a moderate risk of infective endocarditis who may warrant consideration of antibiotic prophylaxis.

SOURCE: Østergaard L, Valeur N, Wang A, et al. Incidence of infective endocarditis in patients considered at moderate risk. Eur Heart J 2019;40:1355-1361.

U.S. guidelines recommend antibiotic prophylaxis for patients at high risk for infective endocarditis (IE). The authors of recent studies have identified patients at moderate risk, but the magnitude of this risk is unclear. Investigators analyzed Danish national patient registries to determine the incidence of IE in patients considered moderate risk.

Moderate-risk patients were defined as those with acyanotic congenital heart valve disease, acquired valve disease, hypertrophic cardiomyopathy (HCM), mitral valve prolapse or regurgitation, and implanted cardiac electrical devices. Each diagnostic category was compared to matched controls without any of these conditions. Researchers also examined patients with prosthetic heart valves as a high-risk comparator group. Patients were followed until another moderate- or high-risk condition developed or 10 years passed. The primary outcome was hospital admission for IE.

Østergaard et al identified 83,453 patients with a left-sided valve disorder, 50,828 with an implanted electrical device, and 3,620 with HCM for a total of 137,901 patients. The median follow-up was 3.7 years. There was a 0.9% incidence of IE in left heart valve disorders, 1.3% in electrical devices, and 0.5% in HCM. Compared to controls, these three conditions led to a higher risk of IE (hazard ratio [HR], 8.75, 6.63, and 6.57, respectively), but were lower than the risk in high-risk patients (HR, 0.27, 0.28, and 0.13, respectively). Further, the 10-year mortality rate was higher in these three groups vs. controls (P < 0.0001). Similar findings were present when those with acyanotic congenital heart valve defects were analyzed. The authors concluded that the cumulative risk of IE in moderate-risk patients at 10 years was about 1%, which was higher than controls but lower than the high-risk population (4.8%).


The authors of a recent paper from England1 identified patient groups at moderate risk for IE, which Østergaard et al corroborated in this study. However, Østergaard et al quantitated the risk as compared to an age- and sex-matched control population and included considerably more clinical details, making comorbidity adjustments more robust. In addition, these authors compared the incidence rates to those of a high-risk subgroup with prosthetic valves. They identified the following moderate-risk groups: left heart valve disease, HCM, and implanted electrical devices. They provided robust data on the these conditions, which showed incidence rates of about 1% (one-fifth to one-quarter the rate in patients with prosthetic valves). Thus, these were truly moderate-risk groups.

Is a 1% risk of IE enough to give antibiotic prophylaxis to everyone in these groups? The authors of the current guidelines thought not, but perhaps there are subgroups who would benefit. For this question, Østergaard et al provided some granularity that could be helpful. For example, they found that implanted defibrillators led to higher rates of IE compared to pacemakers. However, those with any device with more than one lead were at higher risk than those with single-lead devices. Other studies have shown that bicuspid aortic valves and moderate or more regurgitation of a left-sided valve increases the risk of IE. Østergaard et al did not provide these data. Also, other studies have shown that HCM with obstruction is higher risk than without obstruction; again, these authors could not confirm this.

There were other limitations to the Østergaard et al study. The authors lacked autopsy data, which could have reduced IE incidence rates. They did not have data on whether IE was left- or right-sided, nor were there any bacteriologic data. Of course, since this was a retrospective database study, there could have been unmeasured confounders.

Does this study inform my decisions on antibiotic prophylaxis to prevent IE? Yes, it does. It reinforces the prior studies that showed there were moderate-risk patients at significant risk, such as those with left heart valve disease, HCM, and implanted electrical devices. However, it probably is not reasonable to provide prophylaxis to all these patients. As other studies have shown, those with moderate or more regurgitation, bicuspid aortic valves, or obstructive HCM (who probably also have significant mitral regurgitation) certainly are worth considering for antibiotic prophylaxis. The electrical device situation is more complex, as few single-lead devices are placed in the United States now. Most pacemaker patients could be candidates for prophylaxis. Also, lead-related IE is difficult to diagnose, and the consequences of lead IE could be dire for the patient. Thus, I am inclined to recommend prophylaxis for multilead defibrillator and biventricular pacemaker patients, but perhaps not dual-chamber pacemaker patients who are uncomplicated.


  1. Thornhill MH, Jones S, Prendergast B, et al. Quantifying infective endocarditis risk in patients with predisposing cardiac conditions. Eur Heart J 2018;39:586-595.