In 1885, Sir William Osler summarized beautifully the main aspects of clinical infective endocarditis (IE) in the Gulstonian Lectures delivered at the Royal College of Physicians of London. Despite all medical advances in the last 130 years, IE is still associated with substantial morbidity and mortality in the current era. Congenital heart disease (CHD) is a major risk factor for IE. The IE risk is substantially higher in adults with CHD than in the general population, with marked variation between lesions.
Epidemiology
The incidence of IE in the general population is somewhere between 3 and 7 per 100,000 person-years. It is substantially higher in patients with CHD. In children with CHD it is reported to be approximately 4.1 cases per 10,000 person-years (population-based analysis). In adult CHD (ACHD) the incidence is around 11 per 10,000 patient-years with a marked variation between different types of CHD. With the increasing use of interventions, devices like pacemakers ( Fig. 20.1 ) and implantable cardioverter-defibrillators (ICDs), and a CHD population that is getting older, an increase in the incidence of IE can be expected. Interestingly, the risk of women with ACHD to IE is lower than for men ; this is thought to be partly explained by gender differences for underlying types of CHD and partly by different other risk profiles. It is well known that prosthetic valves can act as a nidus for infection within the heart. In the last decade, the technique of percutaneous pulmonary valve implantation (PPVI) has become increasingly common in CHD patients. IE remains a major concern for longer-term outcomes of ACHD after PPVI. Several cases and case series of IE affecting the pulmonary valve implant have been reported subsequently. The reported incidence varies between 1% and 14.3%. The data of one leading European center on PPVI indicated that the person-time incidence rates of IE during a study period from 2009 to 2013 was higher in the PPVI group compared with a surgical treatment group; survival probabilities were similar for both groups, however. There was also a marked difference in the surgical group between the different right ventricular outflow tract (RVOT) conduits used.
As for causative pathogens, Staphylococcus , Streptococcus , and Enterococcus species are responsible for 80% to 90% of IE cases in the general population. A similar pattern has been observed in CHD patients, with Streptococcus and Staphylococcus species most commonly identified.
Infective Endocarditis Prophylaxis
It is assumed that bacteremia subsequent to medical procedures can cause IE, particularly in patients with predisposing factors, and that prophylactic antibiotics may prevent IE in these patients by minimizing or preventing bacteremia. However, there are no randomized controlled data to conclude that antibiotic prophylaxis prevents IE in humans and the efficacy of antibiotic prophylaxis remains unproven. Even if antibiotic prophylaxis does work, the number of cases that need to receive it to prevent one case of IE is not clear and a matter of debate. A recent study using administrative databases to investigate the incidence of IE and the number of prescriptions of prophylactic antibiotics in England gave an estimate of 277 cases.
There are at least some theoretical risks of taking prophylactic antibiotics, like anaphylaxis or the creation of resistant microorganisms. Although there were no reported deaths from amoxicillin when used as a prophylaxis in a recent nationwide study from England, this was not the case for clindamycin. There has been a progressive shift over time since prophylactic antibiotics were first recommended over 50 years ago, to restrict these to fewer and fewer patients and to give smaller doses of antibiotics. In 2008, the United Kingdom National Institute for Health and Clinical Excellence produced new guidelines recommending complete cessation of antibiotic prophylaxis. Other societies such as the European Society of Cardiology and American Heart Association differed in this respect, still recommending prophylactic antibiotics to those patients at highest risk for IE, but only for high-risk dental procedures. Two population-based studies from France and the United States conducted since, with limited antibiotic prophylaxis use for high-risk groups, showed no increase in the incidence of IE. A recent study from the United Kingdom, however, where prophylactic antibiotics were stopped altogether, reported a significant increase in IE. The impact of this dramatic paradigm shift regarding antibiotic prophylaxis on the incidence of IE on ACHD, it is fair to say, is not known.
Antecedent Events
In a substantial number of cases of IE, an antecedent event cannot be identified. In a large cohort of pediatric CHD and ACHD patients with IE, an antecedent event could be identified in only 19% of patients. A study of ACHD patients from the United Kingdom identified an antecedent event in 87 out of 214 episodes of IE (41%). In 42 of these 87 episodes of IE, a previous dental treatment took place at close proximity to the event, and in 17 of these 42 cases antibiotic prophylaxis was given. In another study, appropriate antibiotic prophylaxis for dental-related cases of IE was provided in 50% of cases. These results support the argument that prophylactic antibiotics do not always work, but do not exclude the possibility that they are of value in some situations. It is important to stress that transient bacteremia occurs frequently even in the context of daily routine activities such as tooth brushing, or even chewing. Thus good oral hygiene and regular dental review are of utmost importance to prevent IE. ACHD patients should also be discouraged from getting piercings and tattoos. A prediction model for the risk of developing IE in adulthood for CHD patients turning 18 years of age was recently proposed that includes variables like gender, number of congenital heart defects, type of CHD, history of IE in childhood, a history of cerebrovascular accident in childhood, and a history of supraventricular arrhythmias in childhood. If this model is validated in further studies, it may aid in selection of CHD patients at the highest risk of developing IE, which in turn would be those who would most likely benefit from antibiotic prophylaxis.
Current Recommendations
Although many patients received prophylactic antibiotics for a variety of investigations and procedures in the past, the most recent European guidelines recommend prophylactic antibiotics only for those patients at highest risk for IE and only for high-risk dental procedures. Patients at highest risk for IE are defined as follows:
- 1.
Patients with a prosthetic valve or with prosthetic material used for cardiac valve repair
- 2.
Patients with a previous episode of IE
- 3.
Patients with untreated cyanotic CHD and those with palliative shunts, conduits, or other prostheses
- 4.
Patients with CHD repaired with prosthetic material, whether placed surgically or by percutaneous techniques, up to 6 months after the procedure or lifelong if residual shunt or valvular regurgitation remains
The most recent guidelines of the American Heart Association also recommend prophylactic antibiotics for cardiac transplantation recipients who develop cardiac valvulopathy.
Clinical Presentation
Its diverse nature and highly variable clinical history ensure that IE remains a diagnostic challenge. Although IE may present as an acute, rapidly progressive infection, it is also encountered in subacute forms with nonspecific symptoms. A high index of suspicion is key for diagnosis, especially in high-risk groups like adults with CHD. Unfortunately, a delay between the onset of symptoms and the clinical diagnosis of IE is still often encountered.
Although fever is a common finding, the presence of heart murmurs, which can be helpful in the diagnosis of IE in patients without previous cardiac disease, has limited value in ACHD patients, who often have preexisting heart murmurs. But the clinical finding of an increase or change in the character of the murmur should raise the suspicion of IE. Although laboratory signs of infection like an elevated C-reactive protein or leukocytosis may be helpful, these are nonspecific and are therefore not part of current diagnostic criteria, although endocarditis is rare if they are both normal.
Emboli are a frequent and potentially disastrous complication. Left-sided IE can present with systemic emboli, causing cerebrovascular accidents or infarctions in other organs like the spleen or the kidney. Mitral vegetations of any size are associated with a higher risk of embolization than aortic vegetations, with the highest embolic risk seen with vegetations of the anterior mitral leaflet. Although there is some evidence indicating that the size of the vegetation and the causing microorganism may play a role in increasing the risk of embolization, the risk is significantly lowered after 1 to 2 weeks of appropriate antibiotic therapy. In right-sided IE, septic pulmonary emboli can be found. Some typical clinical manifestations are listed in Table 20.1 .
| Fever |
| Heart murmur (new or increasing) |
Immunologic phenomena/skin lesions
|
| Malaise, fatigue, and weight loss |
| Arthralgia or arthritis |
Embolic complications
|
| Mycotic aneurysms |
| Heart failure |
| Sepsis |
Diagnosis
Echocardiography plays a key role in the diagnosis of IE ( Figs. 20.2 to 20.4 ), but also assists in further management, therapeutic decision making, and monitoring during the disease. Transthoracic echocardiography (TTE) is the first-line imaging modality in suspected IE, but can be limited by suboptimal echocardiographic windows and reduced diagnostic ability if prosthetic material is present. Therefore, in most if not all ACHD patients with suspected endocarditis, a subsequent transesophageal echocardiogram (TEE) may be necessary. An additional strength of TEE is the higher specificity and sensitivity for detecting periannular extension of infection or myocardial abscesses compared with TTE. Echocardiographic findings of vegetations ( Fig. 20.5 ), an abscess, ( Fig. 20.6 ) or new dehiscence of a prosthetic valve are highly suspicious and represent major Duke criteria. If the initial echocardiogram is negative, but clinical suspicion of IE remains high, a repeat examination should be performed after 5 to 7 days. Three-dimensional TEE can provide additional valuable information in selected cases. Furthermore, other imaging techniques like positron emission tomography in combination with computed tomography have recently gained a more prominent role in recent guidelines. These techniques could be especially important in CHD patients, when extracardiac shunts, collaterals, and/or conduits are present, which in turn may be difficult to assess by TTE or TEE.
