Contributed by Brian S. Schwartz, MD
Diagnostic Testing For Cardiac Infections
Cardiac infections are severe, life-threatening infections in many cases. The heart valves (endocardium), myocardium, and pericardium can all be infected. In addition, infection of cardiac devices (pacemakers, defibrillators) is becoming more frequently diagnosed with their increase in use. Diagnosis of cardiac infection can be challenging and usually requires a combination of microbiologic testing and cardiac imaging. Treatment often requires antimicrobial therapy but may also require surgical management for cure.
DIAGNOSTIC TESTING FOR CARDIAC INFECTIONS
An electrocardiogram (ECG) measures electrical activity in the heart using noninvasive monitoring with leads attached to the skin. Cardiac infections can cause disease-specific ECG changes, which can assist in diagnosis.
Echocardiography uses Doppler ultrasound to visualize structures and flow of blood through the heart. The test is very helpful in diagnosing most types of cardiac infections. There are two types of echocardiograms, a transthoracic echocardiogram (TTE), where the probe is placed on the chest wall, and a transesophageal echocardiogram (TEE), where the probe is inserted into the esophagus. The TEE often produces higher-quality images, particularly of aortic and mitral valves, since the TEE probe is closer to the heart itself.
Endocarditis is an infection of the valves of the heart.
Infection of the heart valves is thought to result from the colonization of damaged valvular endothelium by circulating pathogens. Endothelial damage may result from turbulent blood flow around the valve (congenital or rheumatic heart disease), direct injury from foreign bodies (e.g., intravenous catheters), or repeated intravenous injections of particles in intravenous drug users. Organisms enter the bloodstream most often at the site of dental surgery, indwelling intravenous catheters, or intravenous drug use. Adhesion of bacteria to the damaged endothelium is enhanced by their ability to produce a glycocalyx.
Once the infection has begun, a combination of organisms and thrombus organize to form a vegetation (Figure 71–1). Destruction of the valve occurs at different rates depending on the virulence of the organism. As the valve is destroyed, symptoms of valvular regurgitation can develop. Organisms can spread to surrounding myocardium, resulting in abscess formation and destruction of the electrical conduction system. As the vegetation on the valve enlarges, fragments can spread via the bloodstream (emboli), resulting in catastrophic effects, such as cerebrovascular accidents (CVA). Prolonged infection as seen in subacute endocarditis can result in antigen–antibody complex formation. Deposition of these complexes can result in other clinical manifestations as described in the next section. Artificial materials within the heart, such as prosthetic heart valves, pacemakers, and defibrillators, serve as potential sites for infection.
FIGURE 71–1 Endocarditis. Note vegetations on mitral valve. Black arrows point to vegetations. (Reproduced with permission from Longo DL et al (eds). Harrison’s Principles of Internal Medicine. 18th ed. New York: McGraw-Hill, 2012, p 1052. Copyright © 2012 by The McGraw-Hill Companies, Inc.)
The clinical manifestations of infective endocarditis can include any of the following listed below. Depending on the virulence of the infecting pathogen, the time course of illness may be days (acute endocarditis; caused by, for example, Staphylococcus aureus) or weeks to months (subacute endocarditis; caused by, for example, viridans group streptococci).
• Constitutional symptoms: fever (>80% cases), chills, night sweats, anorexia
• Consequences of destruction of heart valves and associated structures: new murmur, heart failure, atrioventricular (AV) block (PR prolongation seen on ECG; Figure 71–2)
FIGURE 71–2 Atrioventricular block with sinus bradycardia. (Reproduced with permission from McKean SC et al. Principles and Practice of Hospital Medicine. New York: McGraw-Hill, 2012. Copyright © 2012 by The McGraw-Hill Companies, Inc.)
• Embolic phenomena:
• Left-sided endocarditis: CVAs or brain abscess (Figure 71–3) (new focal neurologic deficits), splenic or renal infarcts (abdominal or flank pain), and emboli to others sites manifesting as splinter hemorrhages (Figure 71–4), Janeway lesions (Figure 71–5), retinal hemorrhages (Figure 71–6) and conjunctival hemorrhages
FIGURE 71–3 Brain abscess. Red arrow points to a characteristic ring-enhancing lesion. The blue arrows point to two additional abscesses. (Reproduced with permission from Ropper AH, Samuels MA. Adams and Victor’s Principles of Neurology. 9th ed. New York: McGraw-Hill, 2009. Copyright © 2009 by The McGraw-Hill Companies, Inc.)
FIGURE 71–4 Splinter hemorrhage. Red arrow points to a splinter hemorrhage under the finger nail. (Used with permission from Usatine RP et al. The Color Atlas of Family Medicine. New York: McGraw-Hill, 2009. Copyright © 2009 by The McGraw-Hill Companies, Inc.)
FIGURE 71–5 Janeway lesions. Red arrow points to a Janeway lesion. (Used with permission from Wolff K, Johnson R (eds). Fitzpatrick’s Color Atlas & Synopsis of Clinical Dermatology. 7th ed. New York: McGraw-Hill, 2013. Copyright © 2013 by The McGraw-Hill Companies, Inc.)
FIGURE 71–6 Retinal hemorrhages. Blue arrow points to a retinal hemorrhage. (From Usatine RP et al: The Color Atlas of Family Medicine, New York: McGraw-Hill, 2009. Used with permission from Paul D. Comeau.)
• Right-sided endocarditis: septic pulmonary emboli (cough, shortness of breath, chest pain, hemoptysis)
• Antigen–antibody deposition from uncontrolled infection: Osler’s nodes (Figure 71–7), Roth’s spots (Figure 71–8), glomerulonephritis (hematuria), and/or arthritis.
FIGURE 71–7 Osler’s node in pulp of big toe. Red arrow points to an Osler’s node. Note also Janeway lesions on sole of foot. Blue arrow points to a Janeway lesion. (From Usatine RP et al. The Color Atlas of Family Medicine. New York: McGraw-Hill, 2009. Used with permission from David A. Kasper DO, MBA.)
FIGURE 71–8 Roth’s spots. Note the central white spots characteristic of Roth’s spots (red arrow). (From Usatine RP et al. The Color Atlas of Family Medicine. New York: McGraw-Hill, 2009. Used with permission from Paul D. Comeau.)
Bacteria are, by far, the most common causes of endocarditis, but yeasts such as Candida species are involved as well. The modern classification of pathogens causing endocarditis is divided into native valve versus prosthetic valve, with subclassifications within each group (Table 71–1). Among patients with native valve endocarditis who present from the community, viridans group streptococci are the most common pathogens, whereas S. aureus is most common in patients who have had exposure to the health care setting or intravenous drug use. Other important pathogens in native valve endocarditis are Streptococcus bovis (which is associated with colorectal cancer) and Enterococcus species.
TABLE 71–1 Etiology of Endocarditis by Category
In patients who have prosthetic valves, pacemakers, or defibrillators in place, coagulase-negative staphylococci such as Staphylococcus epidermidis, and S. aureus are the most common pathogens. Other less common pathogens that grow relatively well in routine culture media include the β-hemolytic streptococci, Streptococcus pneumoniae, HACEK organisms (Haemophilus aphrophilus and Haemophilus paraphrophilus, Actinobacillus actinomycetemcomitans, Cardiobacterium hominis, Eikenella corrodens, and Kingella kingae), and Candida species. Pathogens that do not grow in routine blood culture media and require specialized testing for diagnosis include Bartonella species, Coxiella burnetii, Brucella species, and Tropheryma whipplei, which are cited as pathogens that cause “culture-negative” endocarditis. The most frequent cause of culture-negative endocarditis is the use of antimicrobials prior to obtaining blood cultures.
A definitive diagnosis of endocarditis requires direct pathologic examination and microbiologic analysis of the heart valve. Because in most cases the heart valve tissue is not available for evaluation, most clinicians use a combination of blood cultures and echocardiographic findings to make the diagnosis of infective endocarditis. The Modified Duke Criteria are the most frequently used criteria for making the diagnosis of endocarditis (Table 71–2) and help guide clinicians to make an accurate diagnosis.
TABLE 71–2 Modified Duke Criteria for the Diagnosis of Infective Endocarditis
Infecting pathogens are most commonly recovered through blood cultures. To maximize sensitivity of the test, it is recommended to obtain three sets of blood cultures over at least an hour. Whenever possible, blood cultures should be obtained prior to administering antibiotics. In some rare cases of endocarditis due to organisms that do not grow easily in blood culture media (Bartonella species), serology can be used to help make the diagnosis.
Evaluation of valves for infection is best accomplished through echocardiography. TTE has reduced sensitivity when compared with TEE to assess for vegetations and myocardial abscesses but is a less invasive test. Not only can echocardiogram identify new vegetations on valves, which are evidence of infection, but it can also assess the degree of valvular damage and complications such as perivalvular abscesses (Figure 71–9). ECG can be used to detect damage to the conducting system. The most common finding is PR prolongation in patients with aortic valve endocarditis and associated perivalvular abscess (see Figure 71–2).
FIGURE 71–9 Transesophageal echocardiography in endocarditis. Segmented abscess cavity (labeled A) between the left atrium (labeled LA) and the aortic root (labeled AO). A red arrow indicates the wall that segments the abscess. RA, right atrium; RVOT, right ventricular outflow tract. (Reproduced with permission from Fuster V et al (eds). Hurst’s The Heart. 13th ed. New York: McGraw-Hill, 2011. Copyright © 2011 by The McGraw-Hill Companies, Inc.)
Without treatment, endocarditis is always fatal, so prompt effective therapy is essential. Bactericidal drugs should be used. The treatment for endocarditis always includes antimicrobial therapy, and in some cases, surgical removal of the infected valve is indicated as well. Empiric therapy for endocarditis is recommended in cases where the patient has hemodynamic instability, severe disease, evidence of embolic disease, or large vegetations. Empiric antimicrobial coverage should be active against methicillin-resistant S. aureus, viridans group streptococci, enterococci, and HACEK organisms. Common empiric regimens include vancomycin plus either ceftriaxone or gentamicin. Specific antimicrobial therapy should be instituted when the results of blood cultures and antibiotic susceptibility tests are known. Antimicrobial therapy for endocarditis is usually required for 4 to 6 weeks.
Surgical therapy is either indicated or should be strongly considered in patients with severe congestive heart failure, perivalvular abscesses, infections refractory to medical management, and embolic events with large vegetations.
In patients with prior endocarditis, a prosthetic heart valve, or select types of congenital heart disease, antibiotic prophylaxis is recommend prior to certain procedures. Guidelines support giving antibiotics, such as amoxicillin, to these high-risk patients at the time of invasive dental procedures (not for routine cleanings), surgery involving respiratory mucosa, or surgery involving infected tissues.
Myocarditis is infection of the heart muscle.
Infection of the myocardium most frequently occurs following hematogenous spread of virus or other pathogen to the heart muscle, although direct spread from adjacent structures can occur. Infection and inflammation of myocardium may result in cardiac dysfunction, leading to heart failure.
Patients with myocarditis present with signs and symptoms of heart failure. Depending on the pathogen, the pace of disease progression may be over days or weeks. Patients may have signs and symptoms of a systemic infection as well (fever, constitutional symptoms). Those with associated pericarditis often have chest pain.
Viral pathogens are thought to be the predominant cause of infectious myocarditis, although many cases are idiopathic. Coxsackie viruses are the most common cause, although cytomegalovirus, Epstein–Barr virus, parvovirus B19, and influenza have been implicated. Other pathogens include Trypanosoma cruzi, the agent of Chagas’ disease, and Trichinella spiralis.
A definitive diagnosis requires cardiac muscle biopsy revealing myocardial inflammation and necrosis. However, most cases are presumptively diagnosed in a patient presenting with heart failure, who has (often global) cardiac dysfunction on echocardiogram and elevated cardiac enzymes. The ECG may be abnormal and may show ST changes mimicking an acute myocardial infarction.
There is no known treatment for most causes of myocarditis, and supportive care is most often given. Patients may ultimately require heart transplant.
There is no known mechanism to prevent myocarditis.
Pericarditis refers to inflammation of the pericardium, which can be due to infection, autoimmune diseases, trauma, or malignancy.
Pathogens reach the pericardium by either hematogenous spread through the blood or direct spread from adjacent intrathoracic structures or, rarely, directly from infected myocardium. Inflammation of the pericardium can result in the formation of pericardial effusion. Pericardial effusions can result in cardiac tamponade. Inflammation can also result in a constrictive physiology. Certain infections causing pericarditis may also be associated with a concomitant myocarditis (see previous “Myocarditis” section).
Chest pain is the most common manifestation of pericarditis. Pain often worsens with inspiration or coughing. Sitting up and leaning forward often improve the pain associated with pericarditis. Patients may have fever and constitutional symptoms. On exam, a friction rub (often consisting of three phases) may be heard when performing auscultation of the heart. This exam finding is very specific for pericarditis. Severe infection may result in cardiac tamponade or constrictive cardiac physiology. These patients present with acute or subacute/chronic onset of symptoms of heart failure, respectively.
Viruses, bacteria, mycobacteria, and fungi have all been reported to cause pericarditis. Among viral infections, Coxsackie virus and echovirus are most common, although human immunodeficiency virus and cytomegalovirus can cause pericarditis as well. Among bacteria, S. aureus and S. pneumoniae are most common. Mycobacterium tuberculosis is one of the most common infectious causes of pericarditis worldwide. Clinical presentation is often subacute and may result in a constrictive pattern. Several fungi such as Histoplasma capsulatum and Coccidioides immitis can cause pericarditis, which clinically presents similarly to tuberculous pericarditis.
Culture of pericardial fluid or pericardial tissue may reveal causative bacteria. Viruses are rarely isolated. Additional diagnostic tests that can help make the diagnosis include ECG that reveals changes in the PR and ST segments. If a significant pericardial effusion is present, the ECG may have reduced amplitude in all leads. An echocardiogram and/or cardiac magnetic resonance imaging will often reveal a pericardial effusion and/or pericardial thickening (Figure 71–10). In addition, chest X-ray may show an enlarged cardiac silhouette (Figure 71–11), and cardiac enzymes can be elevated. Recovery of a pathogen often requires a pericardiocentesis or pericardial biopsy.
FIGURE 71–10 Magnetic resonance imaging of thorax showing pericardial thickening (two black arrows) in patient with constrictive pericarditis. (From Sokolow M, McIlroy MB. Clincial Cardiology, 6th ed. Originally published by Appleton & Lange. Copyright © 1993 by the McGraw-Hill Companies, Inc. Courtesy of C. Higgins.)
FIGURE 71–11 Chest X-ray of a patient with pericardial effusion. Red arrow indicates left border of dilated pericardial sac containing effusion fluid. (Reproduced with permission from Kabbani SS, LeWinter M, in Crawford MH et al (eds). Cardiology. London: Mosby, 2001.)
Treatment for infectious pericarditis is dependent on the pathogen. Most viral etiologies are treated with symptomatic management and supportive care, whereas bacterial, mycobacterial, and fungal infections will require directed antimicrobial therapy. In patients with constrictive pericarditis and tamponade, pericardiocentesis can be life-saving. Untreated bacterial pericarditis is rapidly fatal.
Immunization against S. pneumoniae may be effective. Treatment of early or latent stages of infections (e.g., tuberculosis) may prevent development of pericarditis in some cases.