Stroke and Infective Endocarditis

Abstract & Commentary

By Michael H. Crawford, MD

Source: Dickerman SA, et al The relationship between the initiation of antimicrobial therapy and the incidence of stroke in infective endocarditis: An analysis from the ICE prospective cohort study (ICE-PCS). Am Heart J. 2007;154: 1086-1094.

The appropriate treatment of infective endocarditis (IE), to avoid embolic stroke, is unclear. Thus, Dickerman and colleagues explored the International Collaboration on Endocarditis Prospective Cohort Study (ICE-CPS) database to define the temporal occurrence of stroke in relation to antibiotic therapy. The study population included 1437 patients with left-sided IE who met modified Duke criteria for the diagnosis of IE. The case report forms from 61 centers in 28 countries included 275 variables, including indications for surgery. However, information on vegetation size and mobility was not collected. Most of the patients were male (67%), elderly (mean age 62), and had native valve IE (74%). The numbers with IV drug use or AIDS were small (6 and 2%).

In this cohort, 219 (15%) had a stroke, but incomplete data about the stroke reduced the analyzed population to 185 stroke patients. One half had a stroke prior to antibiotic administration. The daily rate of stroke fell dramatically the second day of antimicrobial therapy. This observation is influenced by the fact that stroke was often the reason for seeking medical attention. If day one is eliminated, the rate of stroke still fell 65% in the second week of therapy (4.82/1000 patient days to 1.7, P < .001). Correction for patients going to surgery did not change the results significantly. After one week of therapy, only 3% of the entire cohort (44/1437) experienced a stroke. Multivariate analysis showed mitral vegetation (P < .0001), S. aureus (P = .01), and intracardiac abscess (P = .02) were significantly associated with stroke. Viridans strep was associated with a lower risk of stroke (P = .04). Overall, 40% of the patients had valvular surgery on the index admission, but only 3.5% had the indication of large mobile vegetations alone. All the rest met standard criteria for surgery. Patients who had surgery had a lower incidence of stroke. There was no subgroup in which antibiotic therapy did not reduce the risk of stroke. Dickerman et al concluded that the risk of stroke falls dramatically after initiation of effective antibiotic therapy and precludes stroke prevention as a sole indicator for valve surgery after one week of therapy.

Commentary

The decision regarding when to operate in patients with IE is difficult because of a lack of randomized, controlled data, as well as the small numbers of patients in observational series. The ICE-PCS gets around the latter problem and, since a randomized, controlled trial of surgery vs medical therapy will never be done, is worth considering. The purpose of this analysis was to determine the relationship between antibiotic therapy and subsequent stroke. The finding that stroke risk decreases rapidly after antibiotic therapy is started confirms the results of older, smaller, often single-center experiences. Also, the results extend to those with any organism and any valve involvement. After one week of effective therapy, stroke risk from that point forward is 1-3%, depending on the valve and the organism. Stroke risk is higher with S. aureus and mitral valve involvement. The practical implications of this information are that antibiotic therapy should be started early in IE and that stroke prevention alone may not be an ndication for surgery. The classical indications for surgery were present in 96.5% of the patients who had surgery (heart failure, significant valve regurgitation, and persistent bacteremia). However, 40% of the patients had surgery, and surgery was associated with a lower risk of stroke. Although large mobile vegetations have been touted as a surgical indication in some studies, not all have found this. In this study, only 3.5% underwent surgery for this indication alone, but we don't know how many patients had this finding and were not operated upon because detailed echo data are not currently in their database. Also, there is no data on prior stroke or embolus (repeated emboli) as an indication for surgery. These issues will have to be the subject of future studies.