Lyme Carditis

Etiology

Lyme disease results from infection with the spirochete Borrelia burgdorferi (B.burgdorferi), in honor of the microbiologist Dr. Willy Burgdorfer, who isolated it in 1982. The natural reservoir for the spirochete includes mice, chipmunks, and other small mammals. Deer are not competent hosts for B.burgdorferi, but they play an important role in sustaining the vector's life cycle, Ixodes tick, which transmits the spirochete. This tick acquires B.burgdorferi by feeding on an infected animal and may transmit the infection to a human during a subsequent blood meal.[1]

Epidemiology

Approximately 30000 cases of Lyme disease are reported annually in the United States; however, the real number can be much higher.[6] In 2015, 95% of cases identified were in the Northeast, mid-Atlantic, and upper Midwest states, and the most affected groups were males between 5 and 9 and 45 to 59 years old.[7] Lyme disease is diagnosed most commonly between March and October, with 60% in June and July.[8] Cardiovascular symptoms are present in approximately 1.5% to 10% of reported cases in the United States. Cases have also been found to be more common in young adult males with a roughly 3 to 1 male-to-female ratio.[2]

Pathophysiology

Replication of B. burgdorferi happens at the site of its inoculation after the tick bite. Following this incident, in a period ranging from a few days to a month, the innate and adaptive cellular immune response arises locally at the site of spirochete entry. After these events, the spirochete, with the help of several proteins and other substances found in the body, spreads to other tissues, including the central nervous system, eye, muscle, liver, spleen, and heart.[1] The immune response activates before and during the organism's dissemination. The body initially activates B-Cell clones to stop this invasion with subsequent elevation of IgM levels. Weeks to months later, the production of IgG directed to different components of B. burgdorferi induces complement fixation and opsonization with consequent bactericidal killing.[1]

The exact mechanism leading to cardiac manifestations is not entirely understood. However, it seems to be an autoimmune inflammatory response to the spirochetes in heart tissue, which causes the abnormalities inducing atrioventricular block. It is possible that cross-reactive IgM antibodies can react with cardiac tissue with consequent injury and functional abnormalities. Researchers have also noted a strong correlation between the number of spirochetes in heart tissue, myocardial inflammation, and the degree of conduction abnormalities.[2] Pathophysiologic events causing Lyme endocarditis are even less clear. No microorganisms usually appear in tissue samples; therefore, diagnostic confirmation is done by other means, including serologic tests and polymerase chain reaction (PCR).[2][3]

Histopathology

The characteristic histopathological finding is an interstitial inflammatory infiltrate containing lymphocytes, histiocytes, and plasma cells. Such infiltrates extend from the endocardium to the epicardium. Neutrophils and eosinophils do not appear in a substantial amount. Spirochetes have been visualized in the epicardium, myocardium, and endocardium using Warthin-Starry stain and immunohistochemistry.[6] However, B.burgdorferi is not always identified. In some case reports of Lyme endocarditis, bacteria appear absent in tissue samples, and other diagnostic methods, such as polymerase chain reaction, have been required to confirm such condition.[2][3] The pathology and localization of infiltrates are not known in less severe cases or during earlier stages of infection in humans.

History and Physical

Lyme carditis must be considered in patients with the typical clinical manifestations of Lyme disease, which usually occurs in various stages. The first phase, early localized infection, is recognized by the characteristic erythema migrans. Following the local manifestation, patients may develop generalized symptoms such as malaise, fever and chills, headache, myalgias, arthralgias, and dizziness as the spirochete continues spreading. It is at this time that cardiac manifestations can arise. Most cases of Lyme carditis occur between June and December. Symptoms are developed from 4 to 7 months after the initial presentation (such as a rash) with a median of 21 days. Patients may initially present the characteristic signs and symptoms of the disease; however, reports indicate that many patients do not recall a tick bite, and the typical rash is present in only 40% of patients with Lyme carditis.[8] The most common symptoms are related to cardiac manifestations, such as heart block, light-headedness, syncope, shortness of breath, palpitations, or chest pain.

The most common objective manifestation of Lyme carditis is atrioventricular conduction block. The degree of atrioventricular block can fluctuate rapidly, progressing from the first-degree to second-degree or complete atrioventricular block and sometimes back to the first-degree in just minutes. Cases of endocarditis with valvular involvement, pericarditis, and myocarditis attributed to Lyme disease have also appeared in the literature. However, these manifestations are reported less commonly than the characteristic conduction-delayed abnormalities.[2][3][9][10] Cases of myopericarditis present with symptoms and electrocardiographic changes similar to acute coronary syndrome; 60% of those patients present with T wave inversion or ST-segment depression. It is rare to find patients with high troponin levels or ST-segment elevation. Valvular involvement with endocarditis is not common; if that is the case, patients usually exhibit signs of acute heart failure and cardiogenic shock.[8]

Evaluation

Atrioventricular block of varying degrees is the most frequent manifestation of Lyme carditis. Therefore, if a patient presents with the characteristic demographic and clinical manifestations, including bradycardia, the next step is to carefully evaluate an electrocardiogram (ECG). Atrioventricular block in Lyme carditis may range from first-degree to complete heart block, also known as third-degree atrioventricular block. The degree of atrioventricular block may change over minutes, hours, or days in these patients.[8] It may be worthwhile to obtain an ECG in young men with early Lyme disease as they are the demographic group most at risk for high-grade conduction deficits.

Atrioventricular block denotes an abnormal P wave and the QRS complex relationship. THE first-degree atrioventricular block characteristically demonstrates a fixed prolongation of the PR interval (greater than 200 milliseconds). The second-degree atrioventricular block displays a progressive prolongation of the PR interval followed by a nonconductive P wave (Mobitz type I) or presents with an unchanged PR interval followed by a single non-conducted P wave (Mobitz type II). In the highest degree of atrioventricular block, there is no atrioventricular conduction in the third degree, and the ECG shows a dissociation between P waves and QRS complexes.[11] Additional studies are not usually necessary if heart block is the only manifestation of Lyme carditis.

Supplementary studies play a more important role when suspecting valvular disease or myocarditis. A chest X-ray may show bilateral infiltrates or pleural effusions.[12] Echocardiography may show mild left ventricular or right ventricular dilation in cases with predominant conduction abnormalities. However, most of the time, the ventricle size remains preserved.[13] Echocardiography may also play a role in differentiating myocarditis from myocardial infarction. In patients with signs and ECG changes characteristics of acute coronary syndrome, echocardiography reveals diffuse ventricular hypokinesis as opposed to focal wall motion abnormalities seen in myocarditis.[13] If difficulty in differentiating between these 2 conditions is present, cardiac MRI merits consideration. In myocarditis, cardiac MRI may show areas of increased epicardial contrast enhancement with no subendocardial involvement, as seen in acute coronary syndrome.[12] 

The gold standard to diagnose infectious diseases continues to be isolating the offending pathogen; this is not the case with B. burgdorferi, which, like some other spirochetes, cannot be cultivated. The diagnosis is based on indirect serologic tests, clinical suspicion, and supporting laboratory and imaging tests. In many cases, clinical suspicion alone may warrant antibiotic treatment. However, many patients may not present the typical manifestations or symptoms, which may be ambiguous. A 2-step method of serologic testing is suggested as the approach to follow. An enzyme-linked immunosorbent assay is the first test to be considered. A Western blot assay is required to confirm the diagnosis if IgM or IgG is positive or borderline.[1] Also, B. burgdorferi DNA was detected in the heart tissue by PCR. PCR can be obtained if the suspected cause of myocarditis or endocarditis is Lyme disease and if the serologic tests for this condition are negative or equivocal when the suspicion is high.[6][8][3]

Treatment / Management

Even though some cases of Lyme carditis can resolve without treatment, antibiotics are indicated to lower the risk of cardiovascular complications, avoid sequela, and shorten the duration of the disease. Beta-lactam antibiotics with demonstrated effectiveness against B. burgdorferi include cephalosporins and tetracyclines. Oral amoxicillin or doxycycline is indicated for mild to moderate disease for 14 to 21 days.[14] Patients with more severe disease require hospitalization. Criteria to admit patients include:(B3)

1. Presence of symptoms such as syncope, dyspnea, or chest pain
2. Atrioventricular block of the second or third-degree
3. Atrioventricular block of first degree with P-R interval greater than or equal to 300 ms

Although there is no evidence indicating the superiority of treatment with parenteral over oral antibiotics, parenteral treatment is the general recommendation for initial treatment in hospitalized patients. Ceftriaxone or cefotaxime is the usual recommended parenteral antibiotic. Intravenous antibiotics should continue until the second or third-degree atrioventricular block resolution or until the P-R interval shortens to under 300 ms. Patients may later continue oral therapy to complete a complete course of 14 to 21 days.[14][15][16] Temporary pacemaker placement is indicated in patients with a combination of hemodynamic instability and high-grade second or third-degree atrioventricular block to avoid. The pacemaker can be removed once the high-degree heart block has been resolved.[17] Since conduction disturbances are transient, resolve with antibiotic treatment, and are not expected to recur, permanent pacemaker placement is not a recommendation. The 2008 American College of Cardiology/American Heart Association/Heart Rhythm Society Guidelines for Device-Based Therapy of Cardiac Rhythm Abnormalities points Lyme carditis out as a class 3 indication.[18] Seronegative Lyme carditis has been documented, so patients with new-onset dilated cardiomyopathy may need treatment with antibiotics.(A1)

Differential Diagnosis

Differential diagnosis for lyme carditis includes:

• Rheumatic fever
• Viral myocarditis
• Systemic lupus erythematosus
• Syphilis
• Bacterial endocarditis

Prognosis

Lyme carditis generally has a good prognosis. It is usually associated with conduction disturbances and is, most of the time, a treatable condition. With adequate antibiotic treatment, the recovery time of patients with third-degree heart block has a median of 6 days. Some cases of persistent atrioventricular block exist, but they are extremely rare.[13] There are reports of death secondary to severe myocarditis. However, there are only a few documented cases with this outcome.[19] A causal link between Lyme disease and dilated cardiomyopathy has been observed.[20] 

Complications

Reports exist of fatal cases; nevertheless, the mortality rate associated with Lyme carditis has always been low and has declined even more as early identification and subsequent antibiotic treatment has improved over time. There was a published report of 3 deaths associated with Lyme carditis in 2013.[21] After this publication, the CDC directed a follow-up investigation, which included 1696 cases reported between 1995 and 2013. Of the 3 cases, only 2 were confirmed as Lyme carditis-associated mortality. This accounts for 0.001% of the total.[22]