on 02-Oct-2022 (Sun)

The interval between an event likely to produce high-grade bacteremia and the onset of symptoms of IE, contrary to older estimates, is quite short. The so-called incubation period in 84% of 76 cases of streptococcal IE was less than 2 weeks.235 On the other hand, the time from onset of symptoms to diagnosis in the subacute form of IE is quite long, with a median interval of approximately 5 weeks.

Symptom duration of cases managed in community hospitals is often shorter than in patients referred to a tertiary care center, reflecting referral bias.4

Four processes contribute to the clinical picture46: (1) the infectious process on the valve, including the local intracardiac complications; (2) bland or septic embolization to virtually any organ; (3) constant bacteremia, often with metastatic foci of infection; and (4) circulating immune complexes and other immunopathologic factors.41–44,46

Important to note, Fernández Guerrero and colleagues found no significant difference in rates of “clinically occult” IE diagnoses before (1970–1985) and after (1986–2008) the availability of echocardiography at their institution (35% vs. 42.8%, respectively).239

Because of its many manifestations, the diagnosis of IE may be delayed; occasionally, it is not clinically suspected and is identified only at postmortem examination.236–238 In a recent postmortem study of IE cases, in 38.2% IE was not diagnosed until autopsy

Fever is common but may be absent (5% of cases), especially in the setting of CHF, renal failure, a terminal disease, older age,240,241 or previous antibiotic therapy. The fever pattern is usually remittent, and the patient’s temperature rarely exceeds 40°C (104°F), except in acute IE

Pulmonary emboli (bland), drug reactions, and nosocomial infection unrelated to IE also are causes of prolonged fever in this patient population

Nonspecific symptoms, such as anorexia, weight loss, malaise, fatigue, chills, weakness, nausea, vomiting, and night sweats, are common, especially in subacute cases.

Traditionally, audible heart murmurs occurred in more than 85% of IE cases. However, recent changes in the epidemiology and microbiology of IE appear to have altered the presentation of IE. For example, in the ICE-PCS experience with more than 2700 prospectively identified IE patients, only 48% had a detectable “new” cardiac murmur, whereas a further 20% exhibited worsening of an existing murmur.7

More than 90% of patients who show a new regurgitant murmur develop CHF. CHF is the leading complication of IE.245

Pericarditis is rare but, when present, usually is accompanied by myocardial abscess forma- tion as a complication of staphylococcal infection

Clubbing is present in 10% to 20% of patients with subacute IE, especially if the disease is of long duration, and may recede with therapy.

Splinter hemorrhages are linear, red-to-brown streaks in the fingernails or toenails and are found commonly in IE. They are a nonspecific finding and are seen often in elderly patients and in patients with occupation-related trauma. These lesions are most suggestive of IE when they are located proximally in the nailbed.

Petechiae are found in 20% to 40% of cases, particularly after a prolonged course, and usually appear in crops on the conjunctivae (see Fig. 80.2), buccal mucosa, palate, and extremities. These lesions initially are red and nonblanching but become brown and barely visible in 2 to 3 days. Petechiae may result from local vasculitis or from emboli

Osler nodes are small, painful, nodular lesions usually found in the pads of fingers or toes and occasionally in the thenar eminence. They are 2 to 15 mm and frequently are multiple and evanescent, disappearing in hours to days. Osler nodes are rare in acute cases of IE but occur in 10% to 25% of subacute cases. They are not specific for IE, because they may be seen in SLE, marantic endocarditis, hemolytic anemia, and gonococcal infections and in extremities with cannulated radial arteries

Janeway lesions (see Fig. 80.3) are hemorrhagic, painless macules with a predilection for the palms or soles. They persist for several days and are believed to be embolic in origin; they occur with greater frequency in staphylococcal IE.

Roth spots (see Fig. 80.4) are oval, pale, retinal lesions surrounded by hemorrhage and usually are located near the optic disk. They occur in fewer than 5% of patients with IE and also may be found in patients with anemia, leukemia, or connective tissue disorders such as SLE.

The frequency of splenomegaly in IE patients has declined significantly in the current era. Among 2662 prospectively enrolled patients with definite IE in whom the finding was recorded, 11% had splenomegaly.7

Splenic septic emboli are common during IE, but localized signs and symptoms are absent in approximately 90% of patients with this complication.247

Serial CT studies usually can be used to distinguish between bland septic emboli and splenic abscess.248

Musculoskeletal manifestations are common in IE. In a review of 192 cases,249 44% of patients had musculoskeletal symptoms. These symptoms usually occurred early in the disease and were the only initial complaint in 15% of cases. They included proximal oligoarticular or monarticular arthralgias (38%), lower-extremity monarticular or oligoarticular arthritis (31%), low back pain (23%), and diffuse myalgias (19%). The back pain may be severe, limiting movement, and may be the initial complaint in 5% to 10% of cases.29

Major embolic episodes, as a group, are second only to CHF as a complication of IE and occur in almost one-fourth of cases.7

Splenic artery emboli with infarction may result in left upper quadrant abdominal pain with radiation to the left shoulder, a splenic or pleural rub, or a left pleural effusion.

Renal infarctions may be associated with microscopic or gross hematuria, but renal failure, hypertension, and edema are uncommon

Retinal artery emboli are rare (<% of cases) and may manifest with a sudden complete loss of vision.

Coronary artery emboli usually arise from the aortic valve and may cause myocarditis with arrhythmias or myocardial infarction. This finding may be overlooked, especially given the time constraints of interventions such as thrombolytic therapy or angioplasty during acute myocardial infarction, resulting in serious complications in patients with IE presenting with an acute myocardial infarction.250

Neurologic manifestations occur in 20% to 40% of all IE cases. In IE cases admitted to intensive care units, however, neurologic manifestations are the most common IE complication, occurring in 55% of patients.251

Patients with S. aureus IE, mitral valve IE, or nonneurologic embolic events are at increased risk for neurologic complications.

Of patients with neurologic complications, 50% present with these signs and symptoms as the heralding features of their illness.252,253

In most episodes (76%), the neurologic manifesta- tion was evident before antimicrobial treatment was started, being the first sign of IE in 47% of episodes.254

Mycotic aneurysms of the cerebral circulation occur in 2% to 10% of cases. They usually are single, small, and peripheral and may lead to devastating subarachnoid hemorrhage.

In the preantibiotic era, renal failure developed in 25% to 35% of the patients, but presently fewer than 10% are affected.

IE may be confused with thrombotic thrombocytopenic purpura if neurologic signs, fever, renal failure, anemia, and thrombocytopenia are present.255

Acute infection accounts for approximately 60% of hospital admissions among injection drug users, and IE is implicated in 5% to 15% of these episodes.256

Although many of the aforementioned clinical manifestations are seen in addicts with IE, several distinctions are noteworthy. In this group of patients, two-thirds have no clinical evidence of underlying heart disease and there is a predilection for the infection to affect the tricuspid valve

Of patients with tricuspid valve infection, 30% have pleuritic chest pain; pulmonary findings may dominate the clinical picture, and the chest radiograph shows abnormalities (e.g., infiltrates, effusion) in 75% to 85% of the cases.261 Radiographic evidence of septic pulmonary emboli is eventually present in 87% of cases.262 Signs of tricuspid insufficiency (gallop rhythm, systolic regurgitant murmur louder with inspiration, large V waves, or a pulsatile liver) are present in only one-third of cases

Conversely, among HIV-infected persons who do not practice injection drug use, IE is rare despite the increasing number of HIV-infected patients worldwide.220 In the absence of injection drug abuse, HIV- seropositive patients develop left-sided and right-sided IE with equal frequency.265

The IE-related morbidity and mortality rates in HIV-seropositive patients who do not have an AIDS-defining illness or criteria are similar to the rates in HIV-seronegative counterparts.265

Hypergammaglobulinemia is detected in 20% to 30% of the cases and may be accompanied by a plasmacytosis in the bone marrow aspirate.

A positive result on assay for rheumatoid factor is found in 40% to 50% of cases, especially when the duration of the illness is more than 6 weeks.200

Hypocomplementemia (reported in 5%–15% of cases) parallels the incidence of abnormal renal function test results (elevated creatinine concentration in 5%–15%).

The urinalysis frequently is abnormal; proteinuria occurs in 50% to 65% of cases, and microscopic hematuria occurs in 30% to 60% of cases. Red blood cell casts may be seen in 12% of cases. Gross hematuria, pyuria, white blood cell casts, and bacteriuria also may be found.

Circulating immune complexes can be detected in most cases of IE but also are found in 32% of patients who have septicemia but no endocarditis, in 10% of healthy persons, and in 40% of noninfected narcotic addicts.200 However, levels of aggregated human immune globulin equivalent to or greater than 100 μg/mL were found only in IE (35% of the cases).

In addition, because the levels decline with appropriate treatment, serial measurement of immune complexes may assist in management of the disease.215,216 Mixed-type cryoglobulins are detectable in 84% to 95% of patients with IE, but this also constitutes a nonspecific finding.

Serial determination of the serum C-reactive protein concentra- tion, although nonspecific and virtually always elevated in IE, may be useful to monitor therapy and detect intercurrent complications or infections.267

The bacteremia is usually continuous and low grade (80% of patients have <273

When bacteremia is present, the first two blood cultures yield the etiologic agent more than 90% of the time.

Specialized methods, and not extended incubation times, are recommended for recovery of fastidious agents of IE.280

Molecular techniques to recover specific DNA or 16S ribosomal RNA from valve tissue samples have been useful diagnostically in selected cases,298 and polymerase chain reaction (PCR) studies performed on blood or serum may be highly useful for the diagnosis of IE caused by difficult-to-grow pathogens.299

In an investigation comparing broad-range PCR results on resected endocardial specimens from 49 patients with suspected IE with results of culture and Gram staining of resected specimens and Duke criteria, bacterial DNA was shown within cardiac tissue in 18% of patients with sterile blood cultures.300