Acquired Heart Disease
RHEUMATIC FEVER
Acute rheumatic fever (RF) has been a scourge of children and young adults for centuries. In the United States, prior to the later half of the 20th century,it remained the leading cause of cardiac disability in the young.28–30It remains the leading cause of heart disease in this population in much
Box 6-3 Cardiac Conditions Associated with Endocarditis
ENDOCARDITIS PROPHYLAXIS RECOMMENDED High-risk category
Prosthetic cardiac valves, including bioprosthetic and homograft valves
Previous bacterial endocarditis
Complex cyanotic congenital heart disease (e.g., single ventricle states, transposition of the great arteries, tetralogy of Fallot)
Surgically constructed systemic pulmonary shunts or conduits
Moderate-risk category
Most other congenital cardiac malformations (other than above and below)
Acquired valvar dysfunction (e.g., rheumatic heart disease)
Hypertrophic cardiomyopathy
Mitral valve prolapse with valvar regurgitation and/or thickened leaflets
ENDOCARDITIS PROPHYLAXIS NOT RECOMMENDED Negligible-risk category (no greater risk than the general
population)
Isolated secundum atrial septal defect
Surgical repair of atrial septal defect, ventricular septal defect, or patent ductus arteriosus (without residua beyond 6 mo)
Previous coronary artery bypass graft surgery Mitral valve prolapse without valvar regurgitation Physiologic, functional, or innocent heart murmurs Previous Kawasaki disease without valvar dysfunction Previous rheumatic fever without valvar dysfunction Cardiac pacemakers (intravascular and epicardial) and
implanted defibrillators
Adapted from Dajani AS,Taubert KA,Wilson W, et al. Circulation 96:358–366, 1997.
of the developing world.31In recent decades, RF has made resurgence in the United States and in other developed countries.29For this reason, it remains an important health problem in most areas of the world.
Etiology
It has been recognized for many decades that there is a clear association of RF with group A β-hemolytic streptococcal (GABHS) infections. As early as the 1930s, certain strains of GABHS and routes of infection were noted to result in RF. Only those strains resulting in pharyngeal infections were associated with RF. Strepto-coccal infections of the skin are not associated with
RF but may result in poststreptococcal glomerulone-phritis (PSG).32–34
Strains of GABHS are identified by their M proteins.
These are found in the cell wall of the organism. Certain M-types are associated with RF, whereas others are associ-ated with PSG.27,32–34The M-types responsible for RF Box 6-4 Dental Procedures and
Endocarditis Prophylaxis
ENDOCARDITIS PROPHYLAXIS RECOMMENDED*
Dental extractions
Periodontal procedures including surgery, scaling and root planing, probing, and recall maintenance Dental implant placement and reimplantation of
avulsed teeth
Endodontic (root canal) instrumentation or surgery only beyond the apex
Subgingival placement of antibiotic fibers or strips Initial placement of orthodontic bands but not
brackets
Intraligamentary local anesthetic injections Prophylactic cleaning of teeth or implants where
bleeding is anticipated
ENDOCARDITIS PROPHYLAXIS NOT RECOMMENDED Restorative dentistry†(operative and prosthodontic)
with or without retraction cord‡
Local anesthetic injections (nonintraligamentary) Intracanal endodontic treatment; postplacement and
buildup
Placement of rubber dams Postoperative suture removal
Placement of removable prosthodontic or orthodontic appllances
Taking of oral impressions Fluoride treatments Taking of oral radiographs Orthodontic appliance adjustment Shedding of primary teeth
Adapted from Dajani AS,Taubert KA,Wilson W, et al. Circulation 96:358–366, 1997.
*Prophylaxis is recommended for patients with high- and moderate-risk cardiac conditions.
†This includes restoration of decayed teeth (filling cavities) and replacement of missing teeth.
‡Clinical judgment may indicate antibiotic use in selected circumstances that may create significant bleeding.
Box 6-5 Other Procedures and Endocarditis Prophylaxis
ENDOCARDITIS PROPHYLAXIS RECOMMENDED Respiratory tract
Tonsillectomy and/or adenoidectomy
Surgical operations that involve respiratory mucosa Bronchoscopy with a rigid bronchoscope
Gastrointestinal tract*
Sclerotherapy for esophageal varices Esophageal stricture dilation
Endoscopic retrograde cholangiography with biliary obstruction
Biliary tract surgery
Surgical operations that involve intestinal mucosa Genitourinary tract
Prostatic surgery Cystoscopy Urethral dilation
ENDOCARDITIS PROPHYLAXIS NOT RECOMMENDED Respiratory tract
Endotracheal intubation
Bronchoscopy with a flexible bronchoscope, with or without biopsy†
Tympanostomy tube insertion Gastrointestinal tract
Transesophageal echocardiography†
Endoscopy with or without gastrointestinal biopsy† Genitourinary tract Uterine dilatation and curettage Therapeutic abortion
Sterilization procedures
Insertion or removal of intrauterine devices Other
Cardiac catheterization, including balloon angloplasty
Implanted cardiac pacemakers implanted defibrillators, and coronary stents
Incision or biopsy of surgically scrubbed skin Circumcision
Adapted from Dajani AS,Taubert KA,Wilson W, et al. Circulation 96:358–366, 1997.
*Prophylaxis is recommended for high-risk patients; it is optional for medium-risk patients.
†Prophylaxis is optional for high-risk patients.
are heavily encapsulated due to larger production of hyaluronic acid. This results in the typical mucoid appear-ance are seen when these organisms are cultured on blood agar. The presence of this thick capsule appears to result in much of the organism’s virulence and may be lost by repeated cultures in blood agar.29,30
Although the precise mechanism remains unknown, it appears clear that M proteins and the virulence of these highly encapsulated strains are essential in the develop-ment of RF. This larger antigen burden results in antigens that cross-react with the infected host, setting up a break-down in the immune tolerance. The result of this action Table 6-4 Prophylactic Regimen for Dental, Oral, Respiratory Tract, and Esophageal Procedures
Situation Agent Regimen*
Standard general prophylaxis Amoxicillin Adults: 2.0 g; children: 50 mg/kg orally 1 hr before procedure Unable to take oral medications Ampicillin Adults: 2.0 g IM or IV; children: 50 mg/kg IM or IV within
30 min before procedure
Allergic to penicillin Clindamycin or Adults: 600 mg; children: 20 mg/kg orally 1 hr before procedure Cephalexin†or cefadroxil†or Adults: 2.0 g; children; 50 mg/kg orally 1 hr before procedure Azithromycin or clarithromycin Adults: 500 mg; children: 15 mg/kg orally 1 hr before procedure Allergic to penicillin and unable Clindamycin or Adults: 600 mg; children: 20 mg/kg IV within 30 min before
to take oral medications procedure
Cefazolin† Adults: 1.0 g; children: 25 mg/kg IM or IV within 30 min before procedure
Adapted From Dajani AS,Taubert KA,Wilson W, et al. Circulation 96:358–366, 1997.
IM,Intramuscularly; IV, Intravenously.
*Total children’s dose should not exceed adult dose.
†Cephalosporins should not be used in individuals with immediate-type hypersensitivity reaction (urticaria, angloedema, or anaphylaxis) to penicillins.
Table 6-5 Prophylactic Regimens for Genitourinary-Gastrointestinal Procedures (Excluding Esophageal Procedures)
Situation Agents* Regimen†
High-risk patients Ampicillin plus gentamicin Adults: ampicillin 2.0 g IM or IV plus gentamicin 1.5 mg/kg (not to exceed 120 mg) within 30 min of starting procedure; 6 hr later, ampicillin 1 g IM/IV or amoxicillin 1 g orally
Children: ampicillin 50 mg/kg IM or IV (not to exceed 2.0 g) plus gentamicin 1.5 mg/kg within 30 min of starting the procedure; 6 hr later, ampicillin 25 mg/kg IM/IV or amoxicillin 25 mg/kg orally
High-risk patients allergic to Vancomycin plus gentamicin Adults; vancomycin 1.0 g IV over 1-2 hr plus gentamicin
ampicillin/amoxicillin 1.5 mg/kg IV/IM (not to exceed 120 mg); complete
injection/infusion within 30 min of starting procedure Children; vancomycin 20 mg/kg IV over 1-2 hr plus
gentamicin 1.5 mg/kg IV/IM; complete injection/infusion within 30 min of starting procedure
Moderate-risk patients Amoxicillin or ampicillin Adults: amoxicillin 2.0 g orally 1 hr before procedure, or ampicillin 2.0 g IM/IV within 30 min of starting procedure
Children: amoxicillin 50 mg/kg orally 1 hr before procedure, or ampicillin 50 mg/kg IM/IV within 30 min of starting procedure
Moderate-risk patients allergic Vancomycin Adults: vancomycin 1.0 g IV over 1-2 hr complete infusion
to ampicillin/amoxicillin within 30 min of starting procedure
Children: vancomycin 20 mg/kg IV over 1-2 hr; complete infusion within 30 min of starting procedure Adapted from Dajani AS,Taubert KA,Wilson W, et al. Circulation 96:358–366, 1997.
IM,Intramuscularly; IV, Intravenously.
*Total children’s dose should not exceed adult dose.
†No second dose of vancomycin or gentamicin is recommended.
is the body forming cross-reactive antibodies to skin, heart tissue, synovial tissue, and the basal ganglia, which are in turn responsible for the pathology seen in RF.29,35
Host factors are also important, both for susceptibility and for clinical expression. An immune competent host is necessary, but it is unclear whether there is a specific genetic predisposition. Attempts to date to isolate spe-cific human haplotypes have been inconclusive.35–37 Clinical presentation may vary with age and sex (chorea is almost never seen in adult males).28,29
Epidemiology
The epidemiology of RF is that of the GABHS and, more specifically, those M-types that are associated with RF. In much of the world, RF remains a disease of poverty and overcrowding. Data from developing countries are often incomplete and conflicting, but certain trends appear to be consistent. High prevalence of RF occurs in areas of increased population density, low socioeconomic status, and rapid urbanization. Access to medical care and nutrition may also be factors.31
In the developed countries, the epidemiology of RF is quite different. RF declined dramatically in the United States over most of the past century. This was associated with improved living conditions as well as public health measures to treat GABHS pharyngitis.28–30Interestingly, the prevalence of GABHS cultured from the pharynx has not decreased dramatically, compared with the fall in RF.
Rather, it is the elimination of the M-types responsible for RF from the population that has resulted in this decline.29 This was shown clearly in the 1980s and 1990s with new outbreaks of RF in the West and among military per-sonnel.38–40The mucoid strains that had previously been eliminated in these areas were again cultured from the affected individuals. These recent clustered outbreaks also occurred predominately in middle-class patients.
The usual environmental factors still seen in developing countries do not appear to be significant in the recent cases in the United States and other developed countries.
Clinical Presentation
There is typically a latent period between GABHS pharyn-gitis and the onset of RF. This usually is 2–3 weeks but may be as short as a week and as long as 6 months. A pro-longed latent phase is more commonly seen in cases presenting with Sydenham’s chorea.28–30
The modified Jones criteria remained a diagnostic standard now, as they have over the last century. Promul-gated by TD Jones in the 1950s, these criteria are still the mainstay for clinical diagnosis for RF. This was reaffirmed in 2002 by the American Heart Association.41They did note that these criteria should not be adhered to rigidly, and that clinical cases may occur that will not fulfill the
criteria. This may be the case where there is a long latent phase or an indolent course of the disease. This results in the patient being assessed for RF perhaps months after the onset of the disease process.
The modified Jones criteria are shown in Box 6-6. The diagnosis of RF requires evidence of a recent GABHS injection plus either one major and two minor criteria or two major criteria. Evidence of a recent GABHS infec-tion is obtained by serologic studies. The most common antibody is antistreptolysin O. Others used included antideoxyribonuclease-B, antidiphosphopyridine nucleoti-dase,and antihyaluronidase.28,29
Major Criteria Arthritis
The arthritis of RF is usually of the large joints: knees, elbows, ankles, and wrists. The joints are hot, erythema-tous in appearance, and tender to palpation. The arthritis is typically migratory. It will usually diminish over several days to a week in an affected joint and will reoccur in unaf-fected joints. It is one of the more common major criteria, occurring in upward of 80% of patients.1In some patients, the initial pattern may be one of increasing multiple joint involvement rather than the typical migratory pattern.30
The arthritis of RF responds well to treatment with either nonsteroidal anti-inflammatory agents (NSAIDs) or corticosteroids. The joints heal without significant seque-lae or deformation. Relapses of the arthritis after initial therapy may occur, requiring repeated courses of anti-inflammatory agents.28
Erythema Marginatum
Erythema marginatum is a serpiginous, blanching, and nonindurated rash. It begins as an area of erythema that spreads with central clearing. It will blanch to pressure and the leading edges will be pinkish or salmon in color.
The rash may be difficult to observe in any but lightly
Box 6-6 Modified Jones Criteria
MAJOR CRITERIA First-degree AV block
Previous rheumatic fever
pigmented individuals. The size and shape of the rash as well as its intensity may change very rapidly.28–30Erythema marginatum is seldom seen in the current era. It usually occurs on the trunk when present. Although a major cri-terion, it is not exclusive to RF and may occur in other clinical settings, notably drug reactions.
Subcutaneous Nodules
Like erythema marginatum, subcutaneous nodules are rarely seen in the current era.29They are small (usually less than 2 cm). They are usually found over the bony prominences and in tendon sheaths.28,29Areas to palpate for subcutaneous nodules include the extensor surfaces of joints, the spinous processes of the vertebrae, the mas-toid process, and the scapulae.
Sydenham’s Chorea
Chorea is often a late finding in RF, with a latent period of up to 6 months. As such, evidence of a recent GABHS infection may be absent by the time it presents.
Nonetheless, patients should receive treatment for GABHS infection upon its diagnosis.29,41
Sydenham’s chorea is characterized by uncoordi-nated, purposeless, involuntary movements of the body and extremities. This motion is usually jerky in nature.
It is usually preceded or accompanied by various degrees of emotional lability. As stated earlier, chorea does not appear in adult men for unknown reasons.29It appears to affect both sexes equally in preadolescent children.28 The chorea is self-limiting. It usually lasts several months but may persist as long as a year.
Carditis
Carditis is the most serious of the clinical presentations of RF, both in its presentation as well as in its long-term con-sequences. Cardiac involvement as rheumatic heart dis-ease is the only significant longterm sequela of RF. The incidence of carditis in first cases of RF is variable and depends on several factors. It appears to be more com-mon in younger patients and may be as high as 90% in very young children. It decreases steadily throughout child-hood and adolescence. The overall incidence for all first cases approaches 50%.28 Carditis is more common in cases of recurrent RF. This is particularly true if carditis had occurred in the primary episode. Residual rheumatic heart disease is the rule after carditis and is more likely and more severe with each subsequent reoccurrence.28,30
The presentation and the extent of carditis in RF may vary from none to life-threatening heart failure. The degree of symptomatology will vary depending on the intensity of the carditis, the type of cardiac involvement, and whether there is already underlying rheumatic heart disease. The carditis is a pancardiac inflammation but may be primarily limited to valvulitis, myocarditis, or peri-carditis in individual cases.
Valvulitis is commonly seen in RF carditis. It is also the cause of most long-term sequelae of rheumatic heart disease. The mitral valve is the most commonly affected valve, followed by the aortic valve. The pulmonary and tricuspid valves are rarely involved. The mitral is affected approximately three times more commonly than the aor-tic valve. Both valves may be affected, but isolated aoraor-tic involvement is more rare.28
In the case of both the aortic and the mitral valve, the primary clinical finding is that of valvular insufficiency. In the mitral valve,this will result in an apical,high-frequency, holosystolic murmur of mitral insufficiency. In severe cases, a mid-diastolic murmur may also be appreciated at the apex. This is due to relative mitral stenosis secondary to leaflet edema and to high flow across the valve as a con-sequence of mitral insufficiency.
Aortic insufficiency will result in the high-frequency, decrescendo diastolic murmur. This is usually best heard at the left midsternal border in the sitting position. It will usually radiate along the left ventricular outflow tract from the apex to the right upper sternal border.
A widened pulse pressure and accentuated pulses by palpation will be present in moderate to severe cases of aortic insufficiency.
Diagnosis of valvulitis can usually be made by careful precordial auscultation.29Echocardiography has become extremely useful in assessing the cardiac function both acutely and as surveillance of long-term rheumatic heart disease.28–30Care must be taken when using echocardio-graphy to diagnose valvulitis, especially in young chil-dren. Current echocardiography machines can detect very trivial amounts of mitral and aortic insufficiency in young children. These are often seen as normal physio-logic findings. They should not be confused as valvulitis in an otherwise normal-appearing heart.
Myocarditis and pericarditis rarely occur without some evidence of valvulitis. When they do occur as iso-lated findings, nonrheumatic origins should be consid-ered.29The findings of myocarditis include tachycardia and gallop rhythm. Echocardiography can diagnose evi-dence of decreased systolic shortening and dilation of the left ventricle. The dilation may occur as a conse-quence of either poor myocardial function or increased stroke volume from concomitant mitral insufficiency, or a combination of both factors.
Pericarditis may result in a friction rub on precordial auscultation. A pericardial effusion is easily seen by echocardiography but may or may not be present.
Electrocardiogram will show the characteristic diffuse ST segment elevations of pericarditis.
Minor Criteria
The minor criteria for RF occur quite commonly. They are nonspecific and so are not highly diagnostic of RF.
Fever
Fever in RF is classically described as initially high-grade and than becoming a chronic low-grade fever after approximately the first week. The initial fever may be as high as 40°C. Low-grade fever from onset of the disease is now more frequently seen.28,29
Elevated Acute-Phase Reactants
The most commonly used acute phase reactants are the erythrocyte sedimentation rate (ESR) and the C-reactive protein (CRP). Both ESR and CRP are indicators of an acute and flammatory response. However, both are non-specific and seen in many disease processes.
Prolonged PR interval
Prolonged PR interval may be found in patients with RF.
But, like other minor criteria, it is nonspecific. It may occur as an incidental finding. It is also associated with other diseases that cause inflammation of the cardiac conduction system, such as Lyme disease.42
Differential Diagnosis
The diagnosis of RF can be very difficult except in the rare classic presentation. Each of the major and minor Jones criteria (with the exception of Sydenham’s chorea) may have a large list of causes if it presents as an isolated finding.
Polyarthritis and fever have a long list of causes in children and adolescents. These include infectious eti-ology such as Lyme disease, rubella, and meningococcal and staphylococcal infections.28,29,41,43Various autoim-mune diseases may present with fever and arthritis, including juvenile rheumatoid arthritis, lupus, and ankylosing spondylitis. The presence of a recent GABHS infection may be helpful in the differentiation from other types of arthritis. Arthritis usually occurs early in the course of RF, when serology titers for GABHS are often high. In the absence of serologic evidence of GABHS infection, other causes of arthritis need to be considered.29
The nature of poststreptococcal reactive arthritis (PSRA) and its relationship with RF remains uncer-tain.29,41This entity consists of a prolonged polyarthri-tis, beginning 3–14 days after GABHS pharyngitis.
The nature of poststreptococcal reactive arthritis (PSRA) and its relationship with RF remains uncer-tain.29,41This entity consists of a prolonged polyarthri-tis, beginning 3–14 days after GABHS pharyngitis.