Embolic Risk in Endocarditis
ABSTRACT & COMMENTARY
By Michael H. Crawford, MD
Professor of Medicine, Chief of Clinical Cardiology, University of California, San Francisco
This article originally appeared in the December 2013 issue of Clinical Cardiology Alert. It was peer reviewed by Ethan Weiss, MD, Assistant Professor of Medicine, Division of Cardiology and CVRI, University of California, San Francisco. Dr. Crawford reports no financial relationships relevant to this field of study, and Dr. Weiss is a scientific advisory board member for Bionovo.
Source: Hubert S, et al. Prediction of symptomatic embolism in infective endocarditis: Construction and validation of a risk calculator in a multicenter cohort. J Am Coll Cardiol 2013;62:1384-1392.
At the time infective endocarditis (IE) is diagnosed, an accurate predictor of the risk of embolic events would help guide the risk/benefit ratio of surgical intervention. Thus, these investigators from two regional centers in France reviewed cases of definite IE by the modified Duke criteria that did not have isolated cardiac device electrophysiologic lead endocarditis or recurrent IE. Embolic events that occurred before diagnosis and the initiation of antibiotic therapy were noted, as well as supporting initial imaging data. The primary endpoint was symptomatic embolic events from the initiation of antibiotic therapy to surgery or 6 months of follow-up. Over the study period, 847 patients met inclusion criteria at the two centers, mean age was 62 years, and 72% were men. Streptococci and staphylococci organisms were causative in half the patients. Prosthetic valve IE occurred in one-fourth of the patients. Head CT scans were performed on admission in 97% and 493 patients had surgery within 30 days. The subjects were randomly divided into a development sample (n = 565) and a validation sample (n = 282). In the total population, 72 had emboli within 14 days and the central nervous system received half. After 6 months, 62% had undergone surgery and 20% had died. The 6-month embolic rate was 8.5% and was highest in the first 2 weeks. In the development group, age, diabetes, atrial fibrillation, previous embolism, vegetation length, and Staphylococcus aureus infection were predictive of emboli. A prediction model based on these variables performed well in the validation sample and can be programmed into a handheld device. The authors concluded that at the diagnosis of IE, a simple calculation of embolic risk can be accurately made that could be useful for therapeutic decisions.
Systemic emboli are common in IE and portend a poor prognosis. Prior studies have shown an association between emboli and vegetation size, staphylococcus infection, and prior embolization, which are characteristics of the infections. These factors highlight the importance of the early deployment of blood cultures and echocardiography in suspected IE. Prior emboli refers to the period before the diagnosis is made and antibiotics are started. The diagnosis of emboli could be made by clinical presentation in symptomatic patients (e.g., stroke) or by imaging in asymptomatic patients. The best imaging approach is not determined by this study, but the importance of prior emboli suggests that brain imaging should be done early to detect silent lesions. Several studies have used MRI for this purpose, but PET is promising and doesn't require contrast. This study adds three patient characteristics that are also strongly associated with emboli: diabetes, atrial fibrillation, and age. These features are combined with the three infection features to provide a risk calculator that can be downloaded on a handheld device. The calculator can be accessed through the electronic version of the paper, in the appendix.
This study and others have shown that after antibiotic therapy is started, the risk of emboli decreases rapidly in the first 2 weeks and is unusual after 4 weeks. Surgical therapy has also been shown to reduce emboli and mortality in selected patients. If surgical therapy is to have an impact on emboli, it needs to be done early. Delays to sterilize the vegetation or other such unproven tactics put the high-risk patient at considerable risk of emboli. Delays that last longer than 2 weeks diminish the potential benefits of surgery for emboli prevention. Surgery beyond 2 weeks is usually done for hemodynamic reasons. In considering early surgery in IE, the potential benefit of surgery has to be balanced against the risk. Estimation of the former has been augmented by this study, because it better identifies the patient at high risk for emboli. Some of these factors used to predict emboli risk also predict surgical risk such as age, so the calculation of surgical risk is complicated in IE patients. If a patient is high risk for emboli and seems low risk for surgery, then early surgery makes sense.
This is a retrospective database study done at two tertiary care centers. Thus, there are referral and selection biases. The study only addresses the prediction of embolic risk by factors discernible early in the course of IE. It does not address the value of surgery, but this has been studied before and there are guidelines for deploying surgical therapy early to prevent emboli. The international guidelines specify prior emboli and vegetation length as factors favoring early surgery in IE patients. This paper adds four more factors to consider and recommends a combined risk score to help with the decision.