Wait, not so fast. Are the new American Heart Association endocarditis prophylaxis guidelines safe, and where is the proof?

With approximately 352,000 infants born annually in Canada (Statistics Canada 2007), and using the congenital heart disease (CHD) incidence rate (eight per 1000 live births), approximately 2800 children with CHD will be born per year in Canada (1). With a total population of 33,000,000 in Canada, approximately 264,000 individuals will have been born with some form of CHD. Others will develop an acquired cardiac condition, such as cardiomyopathy, rheumatic carditis or mitral valve prolapse, which may put them at risk for infective endocarditis (IE). A significant proportion of these individuals will have lifelong cardiac abnormalities, and thus will be at risk for IE.

PROPHYLAXIS

Since 1955, the American Heart Association (AHA) has made recommendations on prophylaxis for individuals with cardiac disorders. Several iterations have been presented, with the most recent 2007 guidelines (2) presenting the most drastic changes – essentially discontinuing prophylaxis, except for a few high-risk individuals. There is a downplaying of procedures as a risk factor for IE. There is tremendous emphasis on daily transient bacteremia from dental brushing and oral care as more likely to cause IE than any dental procedure. It is clear that low-level bacteremia is common, and that other factors must be present to cause IE.

INCIDENCE OF IE

The problem is that IE still occurs in adults and children with cardiac disease throughout the world. It is estimated that there are 11 to 50 cases of IE per million population annually (3). Its incidence is not decreasing; the total number of adult survivors with CHD is now equal to the number of children with CHD in North America (4). In this adult group, many may have residual lesions no longer seen because previous treatments have now been replaced with newer surgical and less invasive techniques. Another concern is that many adults do not know the exact name of their heart problem and may not know their current risk level. The superimposition of other adult medical problems on adult CHD, and its relationship to endocardial injury and IE will remain to be seen.

In Japan (population of 125 million), Niwa et al (5) studied 170 children and 69 adults with IE, between 1997 and 2001, in a national survey. Approximately 50% (119 of 239) of the individuals had previous congenital heart surgery. Streptococci accounted for 50% and staphylococci accounted for 37% of the cultured organisms. Procedures preceding IE included dental (12%) and cardiovascular surgery (8%). There was an 8.8% mortality rate.

In Lyon (France), Di Fillipo et al (6) reported on a single-centre study of 153 children and adults with IE between 1966 and 2001. Dental procedures and dental disease were the leading cause in 20% to 33% of the cases. Lesions included complex cyanotic heart disease and surgically corrected cardiac lesions with prosthetic material. Unoperated ventricular septal defects occurred in 12% of the cases.

In The Netherlands, van der Meer et al (7) reported that of 275 IE patients with known valvular disease, between 8.4% and 17% of IE cases could have been potentially prevented if complete adherence to prophylaxis had been accomplished. Only 25% of these IE patients actually took the recommended prophylaxis. This study contradicts the AHA statement that few, if any, cases of IE are preventable by prophylaxis for dental procedures.

In the recent guidelines (2), the risk for developing IE over a lifetime has been quoted to be five per 100,000 patient-years in the general population compared with 308 per 100,000 patient-years for nontissue valve replacement. For congenital aortic stenosis, the risk is 271 IE cases per 100,000 patient-years, and for ventricular septal defects, the risk is 145 IE cases per 100,000 patient-years. These figures covered the era of more aggressive prophylaxis. Will discontinuing prophylaxis for the majority of individuals with congenital and valvular heart disease result in an increased incidence of IE? How will any change in incidence be monitored by the global health care community caring for these individuals? What degree of change in incidence will be acceptable? Why did the AHA arbitrarily only recommend that the highest-risk group continue to receive prophylaxis? Surely children with mild to moderate native valve congenital aortic stenosis will become significantly threatened by an episode of IE. Why not worry about the lifelong risk of acquiring IE? Each individual with CHD could have a severe outcome with an episode of IE, including significant morbidity, especially if other organs are affected. A small patent ductus arteriosus with related IE can rupture leading to sudden death.

DATA

Animal models show that recent cardiac lesions can be infected by dental procedures. Antibiotic prophylaxis has been shown to reduce this in animal endocarditis models (8).

In 100 children, one to eight years of age, who were undergoing dental procedures while intubated, Lockhart et al (9) showed that amoxicillin decreased the positive blood culture rate from 84% with placebo to 33% with antibiotics.

LACK OF DATA

There are no prospective studies on prophylaxis effectiveness in either children or adults, and conversely no prospective studies on the safety of nonprophylaxis in children or adults with CHD. Medical, legal and ethical barriers have so far made this difficult to study. The studies mentioned in the guidelines involve mainly adults with IE and retrospective analysis of frequency and timing of preceeding dental procedures. It is interesting that the authors of the guidelines recommend further research now that these previous legal and ethical barriers have apparently been dismissed by a consensus report! The Cochrane database (10) in 2004 could not find support for or against IE prophylaxis.

CRITIQUE OF PRIMARY REASONS FOR REVISION OF IE PROPHYLAXIS GUIDELINES BY THE AHA

It is stated that the guidelines had become too complex over 50 years. Actually, the 1997 guidelines are very easy to remember for day-to-day practice and for drug prescribing.

In Table 2 of the guidelines, the first comment is just stating the obvious – the majority of IE cases are from a bacteremia of ‘daily activity’. The wording suggests, however, that bacteremia caused by dental or gastrointestinal/genitourinary procedures is unlikely to have the ability to cause IE, yet animal studies show that they can. If a child has major dental reconstruction or multiple extractions at one sitting under general anaesthesia, can this bacteremia not cause IE?

The second comment of how many cases of IE can be prevented by prophylaxis needs a prospective study, or conversely an assessment of how many increased episodes of IE occur without prophylaxis.

The third comment says that the risk of the antibiotic adverse events outweighs the benefits. With an 8.8% mortality rate, IE seems to far outweigh the minimal side effects most clinicians see in daily practice. In a study in the United Kingdom, Lee and Shanson (11) reported that there had been no deaths from amoxicillin given for prophylaxis. With the known decrease in IE in the experimental animal models, and with decreased bacteremia as noted by Lockhart et al (9), there appears to be evidence that prophylactic antibiotics have a positive role in reducing IE.

Finally, maintaining optimal oral health will likely be achieved by well-motivated, educated individuals and similar to any area of health, there will be a significant number of individuals who will continue to have suboptimal oral health. The guideline authors discredit the benefits of antibiotic prophylaxis in dental procedures and believe that achieving optimal oral health and hygiene may decrease bacteremia. They do not reference any studies in which improved oral health has shown a reduction in bacteremia.

RISK MANAGEMENT

The recent guidelines clearly state that it is not the standard of care, and the guideline authors clearly state that it is a consensus opinion of the committee members. For procedural situations, they clearly state that the individual with cardiac disease, their health care professional and the person doing the procedure need to review what is best for the individual by taking in all factors. Where does that leave the primary care physician, paediatrician and cardiologist? How can we help our patients make the best decision? How do we proceed with so little evidence? Who sets the standard of care for Canadians? Two authors in The Canadian Journal of Cardiology (12) recommend supporting the AHA guidelines, but as pointed out by Stone et al (13) in the same journal, stakeholder involvement as well as piloted use of the guidelines by Canadian cardiologists is needed to ensure integration and harmonization of clinical practice guidelines.

It would appear that the best approach is to know the case of each individual with cardiac disease, to assess whether they are at risk for IE and to rank that risk as low, moderate or high. All factors including overall determinants of health, immune status, oral and skin health need to be assessed. Children and their parents need to be taught how to keep their skin healthy and how to address skin infections appropriately. Likewise, oral health needs to be taught, assessed and maintained. Waiting until four years of age may be too late for a child’s first dental visit. Unfortunately, some patients will continue to have poor oral health and may pose a greater risk for IE, either with procedures or on a daily basis. In the end, until a randomized controlled study is performed, the parent and patient will have to decide how much known and unknown risk they are comfortable with. Individuals with CHD should be informed about the signs and symptoms of IE.

Documentation of the discussion about prophylaxis and approach selected by the individual at risk is important. A number of individuals, particularly those with aortic valve disease, may choose to wait to see how the new guidelines perform before switching to them. For most paediatric cardiologists in Canada, how to counsel moderate-risk patients – most congenital patients – will be time consuming. Due diligence, critical analysis and prudence are the important steps to take.

SUGGESTED PLAN OF ACTION

The paediatric community should be able to track the incidence of IE across Canada using the Canadian Paediatric Surveillance Program. Factors affecting the acquisition of IE in children will allow us to focus on possible preventive initiatives, including rational prophylaxis measures. This is currently being formulated (M Béland, personal communication).

Primary care providers should develop early dental oral health initiatives for children with the eruption of primary teeth at six to 12 months of age as per the American Dental Association (14). The first dental health visit should occur around this time and should be supported by provincial health programs to make a lifelong impact on oral health and reduce both nosocomial- and intervention-related risks for IE and other health-related issues. The Canadian Paediatric Society and the Canadian Academy of Paediatric Dentistry could look at models of early education, assessment and intervention. Pilot programs with children with CHD could help with more widespread programs for all children.

A prospective, multicentre, Canadian study of children and adults with CHD should be followed for five to 10 years to assess IE incidence, risk factors and strategy assessment in reducing IE in this population. Alternatively, an IE national study similar to the Japanese study by Niwa et al (5) could provide a national perspective on IE in Canada. Such a study could help the Canadian Cardiovascular Society in making recommendations for the Canadian population.

Further research, including a chronic animal model for IE, may help delineate why certain individuals develop IE and others do not.

SUMMARY

IE still occurs in children and adults with and without known cardiac disease. An unknown number of cases may be preventable. In fact, a significant number may be preventable by better education and management of skin and oral hygiene. Significant morbidity and mortality still occur with IE, and thus, cost-effective ways of reducing the risk of IE using a prevention approach will still require certain prophylaxis measures in certain situations. The safety of the individual with CHD, with respect to IE, needs to be maximized due to the associated significant morbidity and mortality. Let the research continue.