Matthew E. Levison

Diagnosis, Treatment, and Long-Term Management of Kawasaki Disease A Statement for Health Professionals From the Committee on Rheumatic Fever, Endocarditis and Kawasaki Disease, Council on Cardiovascular Disease in the Young, American Heart Association

Background—Kawasaki disease is an acute self-limited vasculitis of childhood that is characterized by fever, bilateral nonexudative conjunctivitis, erythema of the lips and oral mucosa, changes in the extremities, rash, and cervical lymphadenopathy. Coronary artery aneurysms or ectasia develop in ≈15% to 25% of untreated children and may lead to ischemic heart disease or sudden death. Methods and Results—A multidisciplinary committee of experts was convened to revise the American Heart Association recommendations for diagnosis, treatment, and long-term management of Kawasaki disease. The writing group proposes a new algorithm to aid clinicians in deciding which children with fever for ≥5 days and ≤4 classic criteria should undergo echocardiography, receive intravenous gamma globulin (IVIG) treatment, or both for Kawasaki disease. The writing group reviews the available data regarding the initial treatment for children with acute Kawasaki disease, as well for those who have persistent or recrudescent fever despite initial therapy with IVIG, including IVIG retreatment and treatment with corticosteroids, tumor necrosis factor-&agr; antagonists, and abciximab. Long-term management of patients with Kawasaki disease is tailored to the degree of coronary involvement; recommendations regarding antiplatelet and anticoagulant therapy, physical activity, follow-up assessment, and the appropriate diagnostic procedures to evaluate cardiac disease are classified according to risk strata. Conclusions—Recommendations for the initial evaluation, treatment in the acute phase, and long-term management of patients with Kawasaki disease are intended to assist physicians in understanding the range of acceptable approaches for caring for patients with Kawasaki disease. The ultimate decisions for case management must be made by physicians in light of the particular conditions presented by individual patients.

Diagnosis, Treatment, and Long-Term Management of Kawasaki Disease: A Statement for Health Professionals From the Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease, Council on Cardiovascular Disease in the Young, American Heart Association

Background. Kawasaki disease is an acute self-limited vasculitis of childhood that is characterized by fever, bilateral nonexudative conjunctivitis, erythema of the lips and oral mucosa, changes in the extremities, rash, and cervical lymphadenopathy. Coronary artery aneurysms or ectasia develop in ∼15% to 25% of untreated children and may lead to ischemic heart disease or sudden death. Methods and Results. A multidisciplinary committee of experts was convened to revise the American Heart Association recommendations for diagnosis, treatment, and long-term management of Kawasaki disease. The writing group proposes a new algorithm to aid clinicians in deciding which children with fever for ≥5 days and ≤4 classic criteria should undergo electrocardiography, receive intravenous gamma globulin (IVIG) treatment, or both for Kawasaki disease. The writing group reviews the available data regarding the initial treatment for children with acute Kawasaki disease, as well for those who have persistent or recrudescent fever despite initial therapy with IVIG, including IVIG retreatment and treatment with corticosteroids, tumor necrosis factor-α antagonists, and abciximab. Long-term management of patients with Kawasaki disease is tailored to the degree of coronary involvement; recommendations regarding antiplatelet and anticoagulant therapy, physical activity, follow-up assessment, and the appropriate diagnostic procedures to evaluate cardiac disease are classified according to risk strata. Conclusions. Recommendations for the initial evaluation, treatment in the acute phase, and long-term management of patients with Kawasaki disease are intended to assist physicians in understanding the range of acceptable approaches for caring for patients with Kawasaki disease. The ultimate decisions for case management must be made by physicians in light of the particular conditions presented by individual patients.

Update on Cardiovascular Implantable Electronic Device Infections and Their Management A Scientific Statement From the American Heart Association

Despite improvements in cardiovascular implantable electronic device (CIED) design, application of timely infection control practices, and administration of antibiotic prophylaxis at the time of device placement, CIED infections continue to occur and can be life-threatening. This has prompted the study of all aspects of CIED infections. Recognizing the recent advances in our understanding of the epidemiology, risk factors, microbiology, management, and prevention of CIED infections, the American Heart Association commissioned this scientific statement to educate clinicians about CIED infections, provide explicit recommendations for the care of patients with suspected or established CIED infections, and highlight areas of needed research.

Periodontal Disease and Atherosclerotic Vascular Disease: Does the Evidence Support an Independent Association? A Scientific Statement From the American Heart Association

A link between oral health and cardiovascular disease has been proposed for more than a century. Recently, concern about possible links between periodontal disease (PD) and atherosclerotic vascular disease (ASVD) has intensified and is driving an active field of investigation into possible association and causality. The 2 disorders share several common risk factors, including cigarette smoking, age, and diabetes mellitus. Patients and providers are increasingly presented with claims that PD treatment strategies offer ASVD protection; these claims are often endorsed by professional and industrial stakeholders. The focus of this review is to assess whether available data support an independent association between ASVD and PD and whether PD treatment might modify ASVD risks or outcomes. It also presents mechanistic details of both PD and ASVD relevant to this topic. The correlation of PD with ASVD outcomes and surrogate markers is discussed, as well as the correlation of response to PD therapy with ASVD event rates. Methodological issues that complicate studies of this association are outlined, with an emphasis on the terms and metrics that would be applicable in future studies. Observational studies to date support an association between PD and ASVD independent of known confounders. They do not, however, support a causative relationship. Although periodontal interventions result in a reduction in systemic inflammation and endothelial dysfunction in short-term studies, there is no evidence that they prevent ASVD or modify its outcomes.

Diagnosis and Management of Infective Endocarditis and Its Complications

Infective endocarditis (IE) carries a high risk of morbidity and mortality. Rapid diagnosis, effective treatment, and prompt recognition of complications are essential to good patient outcome. Therapy of IE caused by the more commonly encountered organisms, including streptococci, enterococci, staphylococci, and the HACEK organisms ( Hemophilus parainfluenzae, Hemophilus aphrophilus, Actinobacillus [Hemophilus] actinomycetemcomitans, Cardiobacterium hominis, Eikenella species , and Kingella species), has been addressed previously by this committee.1 Likewise, the antimicrobial prevention of endocarditis has also been previously addressed.2 In this article, we review and update the current literature with respect to diagnostic challenges and strategies, difficult therapeutic situations, and management choices in patients with IE. This article focuses predominantly on adults with IE. A separate article, currently in preparation, will address the issues of IE in childhood. ### Clinical Criteria The diagnosis of IE is straightforward in those patients with classic oslerian manifestations: bacteremia or fungemia, evidence of active valvulitis, peripheral emboli, and immunologic vascular phenomena. In other patients, however, the classic peripheral stigmata may be few or absent.3 This may occur during acute courses of IE, particularly among intravenous drug abuse (IVDA) patients in whom IE is often due to Staphylococcus aureus infection of right-sided heart valves, or in patients with IE caused by microorganisms such as HACEK. Acute IE evolves too quickly for the development of immunologic vascular phenomena, which are more characteristic of subacute IE. In addition, acute right-sided IE valve lesions do not create the peripheral emboli and immunologic vascular phenomena that can result from left-sided valvular involvement.3 The variability in the clinical presentation of IE requires a diagnostic strategy that will be both sensitive for disease detection and specific for its exclusion across all the forms of the disease. In 1981, von Reyn et al4 proposed a scheme for strict case definitions of IE …

Infective Endocarditis in Adults: Diagnosis, Antimicrobial Therapy, and Management of Complications: A Scientific Statement for Healthcare Professionals From the American Heart Association.

Background— Infective endocarditis is a potentially lethal disease that has undergone major changes in both host and pathogen. The epidemiology of infective endocarditis has become more complex with today‘s myriad healthcare‐associated factors that predispose to infection. Moreover, changes in pathogen prevalence, in particular a more common staphylococcal origin, have affected outcomes, which have not improved despite medical and surgical advances. Methods and Results— This statement updates the 2005 iteration, both of which were developed by the American Heart Association under the auspices of the Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease, Council on Cardiovascular Disease of the Young. It includes an evidence‐based system for diagnostic and treatment recommendations used by the American College of Cardiology and the American Heart Association for treatment recommendations. Conclusions— Infective endocarditis is a complex disease, and patients with this disease generally require management by a team of physicians and allied health providers with a variety of areas of expertise. The recommendations provided in this document are intended to assist in the management of this uncommon but potentially deadly infection. The clinical variability and complexity in infective endocarditis, however, dictate that these recommendations be used to support and not supplant decisions in individual patient management.

Hospital-acquired Infection with Vancomycin-resistant Enterococcus faecium Transmitted by Electronic Thermometers

OBJECTIVES To describe an epidemic of vancomycin-resistant Enterococcus faecium causing bacteremia and bacteriuria, to identify the source of infection, to delineate risk factors associated with acquisition of the organism, and to determine antibiotic sensitivities for the organism. DESIGN Investigation of an epidemic, including a case-control study. SETTING Medical-surgical intensive care unit and ward in a university medical center. PATIENTS Nine patients infected or colonized with vancomycin-resistant Enterococcus faecium and 20 noninfected controls. MEASUREMENTS Clinical data, environmental surveillance cultures, and in-vitro microbiologic studies. RESULTS Colonization or infection by vancomycin-resistant E. faecium was associated with an increased duration of treatment with ceftazidime, 13.2 compared with 4.6 days, and a greater number of nonisolated days of hospitalization in the intensive care unit, 19.9 compared with 6.4 days for infected and noninfected patients, respectively (P less than 0.05). Environmental surveillance cultures recovered the organism repeatedly from the rectal probe handles of three electronic thermometers used exclusively on nonisolated patients in the intensive care unit. Restriction endonuclease analysis of plasmid DNA showed that all clinical and environmental isolates were identical. Infection control measures, including isolation of colonized or infected patients and removal of the rectal thermometer probes suspected to be responsible for transmission, resulted in termination of the outbreak. In-vitro, time-kill studies showed that the combination of ciprofloxacin, rifampin, and gentamicin resulted in bactericidal activity against the organism. CONCLUSIONS This nosocomial outbreak of infection due to a highly vancomycin-resistant strain of Enterococcus is the first epidemic in which an electronic thermometer has been implicated as the vehicle of transmission for an infectious agent.

Dental and Cardiac Risk Factors for Infective Endocarditis: A Population-Based, Case-Control Study

Infective endocarditis is uncommon but potentially fatal. Administration of antibiotic prophylaxis is conventional [1], but data supporting its effectiveness derive solely from anecdotal reports, studies of bacteremia after dental and other procedures, and animal models. The low incidence of disease [2] has made randomized human trials of antibiotic effectiveness impractical. Even if effective, antibiotic prophylaxis should be reserved for patients at increased risk, such as those with cardiac abnormalities who are undergoing dental procedures. However, controlled human studies of risk factors are lacking. Previous case series indicate that approximately 15% of patients with infective endocarditis caused by mouth organisms had undergone a recent dental procedure [3], but the comparable percentage from a general population is unknown. The single hospital-based casecontrol study did not find an elevated risk associated with dental therapy, except for a borderline increase with dental scaling [4]. We are unaware of controlled human studies that quantify the risk for infective endocarditis associated with cardiac valve abnormalities other than mitral valve prolapse. We therefore conducted a population-based casecontrol study to evaluate and quantify risk factors for infective endocarditis, especially those considered by the American Heart Association (AHA) to be indications for antibiotic prophylaxis [1]. Methods Participants From August 1988 to November 1990, we maintained surveillance for infective endocarditis in 54 hospitals of the Delaware Valley Case-Control Network, a population-based network of hospitals in the eight counties that constitute the Philadelphia Metropolitan Statistical Area and the county of New Castle, Delaware. Patients with a putative diagnosis of infective endocarditis were identified by hospital personnel and were reported to study nurses, who also actively sought cases. To assess the completeness of ascertainment, five high-yield hospitals and three low-yield hospitals were asked to list all patients discharged with a diagnosis of endocarditis over 3 months. These lists were compared with those obtained from our surveillance; charts were reviewed when differences were identified. We obtained informed consent from physicians and case-patients, then used structured forms to abstract medical records, including echocardiographic reports and hospital laboratory information on the infecting organism. We deleted information on purported risk factors for infective endocarditis and submitted these records for review by three of the authors, who are consultants in infectious diseases recognized for their expertise in infective endocarditis [5, 6]. These experts used their own global clinical judgment to classify potential cases as definite, probable, or possible cases or probable noncases. Agreement of two of the three reviewers was required to make the determination of a case or a noncase [6]. One control from the community was selected for each case-patient by using a modification of the Waksberg random-digit dialing method [7]. Controls and case-patients were matched for age (in 5-year strata), sex, and neighborhood of residence (by using area code, telephone exchange, and the first subsequent digit of the case-patients telephone number). We excluded from these analyses patients with infective endocarditis who were younger than 18 years of age, intravenous drug users, and patients who developed endocarditis in the hospital. This study received separate institutional review board approval at the University of Pennsylvania and all 54 participating hospitals. Data Collection Information was obtained from case-patients by conducting a structured telephone interview after hospital discharge. The date of hospital admission served as the study date for case-patients; for controls, the date of the telephone interview was used. Telephone interviewers collected information on demographic characteristics; diagnostic and therapeutic medical and dental procedures in the year before the study date; potential host risk factors, including preexisting cardiac lesions, preexisting local infection, risk factors for oral or dental disease, diabetes mellitus, immune deficiencies, family history of endocarditis, alcoholism, malignant conditions, and autoimmune disease; previous antibiotic use; and other recent illnesses. For each host risk factor, we requested the date of diagnosis, diagnostic method (for example, echocardiography for mitral valve prolapse), and the name of the practitioner who made the diagnosis. For each medical and dental procedure, we sought information about the procedure, the month and year in which it was performed, and the practitioner. We requested medical and dental records describing procedures and validating individual diagnoses. Study Variables Case-patients were considered infected with dental flora if the organism found was viridans streptococci; nutritionally variant streptococci; Actinobacillus species; Cardiobacterium hominis; anaerobes; -hemolytic streptococci (not group D); unspecified streptococci; or Haemophilus, Eikenella, Kingella, or Neisseria species. Because this study focused on indications for antibiotic prophylaxis, we examined host characteristics reported by patients as the primary risk factor variables, reflecting the information that would be available to a practitioner about to perform a procedure for which prophylaxis might be indicated. A variable called any valvular heart abnormality was defined as the presence of any of the following self-reported, preexisting conditions: mitral valve prolapse, congenital heart disease, history of rheumatic fever with heart involvement, prosthetic heart valve, previous episode of endocarditis, or other valvular heart disease. Dental visit information was obtained solely from dental records. Dental hygiene care was defined as preventive oral health services and therapeutic services, including coronal scaling and polishing. Consistent with AHA guidelines, invasive dental procedures were defined to include dental hygiene care, extractions, periodontal treatment (including scaling and root planing), endodontic treatment, mouth or gingival surgery, and treatment of tooth abscess. Noninvasive dental procedures were simple restorations, prosthetic and restorative dentistry, fluoride treatment, and other procedures (prosthetic services, including adjustments and suture removal). Unless otherwise specified, dental treatment refers to all dental treatment and is not limited to invasive procedures. Initial analyses focused on dental procedures performed at any time in the 3 months before the study date. Analyses were then narrowed to 2 months and 1 month before the study date. Time frames are approximate because the onset of infective endocarditis is often difficult to determine with certainty. We therefore chose the date of hospital admission as the study date, collected procedural data based on month rather than on a specific date, and calculated time frames under the assumption that procedures were performed on the 15th of the month. Statistical Analysis Frequencies and cross-tabulations between casecontrol status and potential risk factors were obtained. Conditional logistic regression was used to determine the independent effects of the various potential risk factors and the possibility of any interactions among factors [8]. Variables were included in multiple regression models if they were significant (P < 0.2) in unadjusted (matched) analyses (such as kidney disease and diabetes), if their inclusion had a substantial effect (>15% change) on coefficients for variables already in the model (such as insurance status) [9], or if they were strongly suspected a priori of being confounders (such as ethnicity). For analyses specific to participants with known cardiac valvular abnormalities, odds ratios and CIs were calculated from a model that included main effects for cardiac valvular abnormalities and dental treatment and the interaction between those variables. The odds ratio for various dental therapy variables among participants with cardiac valvular abnormalities was estimated by combining coefficients for the dental therapy variable and the interaction term. The CI for this combination of coefficients was estimated by using the appropriate variance and covariance terms [8]. With the interaction terms, participants with and those without valvular abnormalities were included in these analyses. Exact odds ratios and CIs, stratified on the matching variables, were calculated when data were too sparse for conditional logistic regression [10]. We used SAS statistical software (SAS Institute Inc, Cary, North Carolina) for data management and to obtain frequencies and cross-tabulations. We used EGRET (Epidemiological Graphics, Estimation and Testing software, version 0.25.1, Cytel Software Corp., Cambridge, Massachusetts) for conditional logistic regressions and exact analyses. All CIs are 95%, and all P values are two-sided. The sample size for the study was chosen so that by assuming an level of 0.05 (two-sided) and a power of 80%, we would be able to detect associations with an odds ratio of 2.0 or more for risk factors with a prevalence between 0.1 and 0.8. Results Participants We identified and recruited 416 potential case-patients (Figure 1). Our assessment process confirmed that more than 90% of true cases of infective endocarditis had been identified. The expert panel judged 379 patients to have definite, probable, or possible infective endocarditis; 37 (9%) were judged to be probable noncases and were excluded. Agreement among judgments was high, ranging from 92% to 96% [6]. Figure 1. Enrollment of case-patients. Of these 379 patients, 287 had community-acquired infective endocarditis not associated with intravenous drug use (248 on native valves and 39 on prosthetic valves), 27 had nosocomial infective endocarditis (18 on nativ

Nonvalvular Cardiovascular Device–Related Infections

More than a century ago, Osler took numerous syndrome descriptions of cardiac valvular infection that were incomplete and confusing and categorized them into the cardiovascular infections known as infective endocarditis. Because he was both a clinician and a pathologist, he was able to provide a meaningful outline of this complex disease. Technical advances have allowed us to better subcategorize infective endocarditis on the basis of microbiological etiology. More recently, the syndromes of infective endocarditis and endarteritis have been expanded to include infections involving a variety of cardiovascular prostheses and devices that are used to replace or assist damaged or dysfunctional tissues (Table 1). Taken together, infections of these novel intracardiac, arterial, and venous devices are frequently seen in medical centers throughout the developed world. In response, the American Heart Association’s Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease wrote this review to assist and educate clinicians who care for an increasing number of patients with nonvalvular cardiovascular device–related infections. Because timely guidelines1,2 exist that address the prevention and management of intravascular catheter–related infections, these device-related infections are not discussed in the present Statement. View this table: TABLE 1. Nonvalvular Cardiovascular Device–Related Infections This review is divided into two broad sections. The first section examines general principles for the evaluation and management of infection that apply to all nonvalvular cardiovascular devices. Despite the marked variability in composition, structure, function, and frequency of infection among the various types of nonvalvular cardiovascular devices reviewed in this article, there are several areas of commonality for infection of these devices. These include clinical manifestations, microbiology, pathogenesis, diagnosis, treatment, and prevention. The second section addresses each device and describes unique clinical features of infection. Each device is placed into one of 3 categories—intracardiac, arterial, or venous—for discussion. ### Clinical Manifestations The specific signs and symptoms associated with an infection of a …

Prevention of bacterial endocarditis. Recommendations by the American Heart Association.

Objective To update recommendations issued by the American Heart Association last published in 1990 for the prevention of bacterial endocarditis in individuals at risk for this disease. Participants An ad hoc writing group appointed by the American Heart Association for their expertise in endocarditis and treatment with liaison members representing the American Dental Association, the Infectious Diseases Society of America, the American Academy of Pediatrics, and the American Society for Gastrointestinal Endoscopy. Evidence The recommendations in this article reflect analyses of relevant literature regarding procedure-related endocarditis, in vitro susceptibility data of pathogens causing endocarditis, results of prophylactic studies in animal models of endocarditis, and retrospective analyses of human endocarditis cases in terms of antibiotic prophylaxis usage patterns and apparent prophylaxis failures. MEDLINE database searches from 1936 through 1996 were done using the root words endocarditis, bacteremia, and antibiotic prophylaxis. Recommendations in this document fall into evidence level III of the US Preventive Services Task Force categories of evidence. Consensus Process The recommendations were formulated by the writing group after specific therapeutic regimens were discussed. The consensus statement was subsequently reviewed by outside experts not affiliated with the writing group and by the Science Advisory and Coordinating Committee of the American Heart Association. These guidelines are meant to aid practitioners but are not intended as the standard of care or as a substitute for clinical judgment. Conclusions Major changes in the updated recommendations include the following: (1) emphasis that most cases of endocarditis are not attributable to an invasive procedure; (2) cardiac conditions are stratified into high-, moderate-, and negligible-risk categories based on potential outcome if endocarditis develops; (3) procedures that may cause bacteremia and for which prophylaxis is recommended are more clearly specified; (4) an algorithm was developed to more clearly define when prophylaxis is recommended for patients with mitral valve prolapse; (5) for oral or dental procedures the initial amoxicillin dose is reduced to 2 g, a follow-up antibiotic dose is no longer recommended, erythromycin is no longer recommended for penicillin-allergic individuals, but clindamycin and other alternatives are offered; and (6) for gastrointestinal or genitourinary procedures, the prophylactic regimens have been simplified. These changes were instituted to more clearly define when prophylaxis is or is not recommended, improve practitioner and patient compliance, reduce cost and potential gastrointestinal adverse effects, and approach more uniform worldwide recommendations.