Risk factors for Lyme carditis: A case-control study

Lyme disease (LD), caused by the spirochete Borrelia burgdorferi, is one of the most prevalent tick-borne diseases worldwide. The acquisition of the infection occurs 7–28 days after experiencing a bite from an Ixodes scapularis tick, ¹ with the classic of erythema migrans (EM) or “bull’s eye rash.” When diagnosis fails during the early course of the disease, B. burgdorferi may invade other organ tissues such as the heart and joints, causing carditis and arthritis, respectively.^1,2 Of all LD syndromes, one of particular concern is carditis because of its association with morbidity and mortality. Lyme carditis (LC) was first reported in 1980. ³ LC is caused by direct invasion of myocardial tissue by spirochetes and an immunological host response causing lymphocyte inflammation. B. burgdorferi has a predisposition to cause inflammation of the atrioventricular (AV) node resulting in variable conduction abnormalities which can be seen in electrocardiograms (ECGs/EKGs), ⁴ such as atrioventricular conduction abnormalities (most common), right bundle branch block (RBBB), and left bundle branch block (LBBB). ³ Furthermore, cases of LC with widening of the QRS complex, AV dissociation, atrial fibrillation, ventricular dysfunction, fulminant myocarditis, and even cardiac arrest have been described.^3–5 While LC is not commonly present during early LD, disseminated EM and LC may present concurrently within two weeks of tick attachment. ⁶ Furthermore, single EM concomitantly with an AV block has been also reported. ⁷ LC is reported to occur in 4–10% of untreated LD cases and is usually present 2–5 weeks after EM rash or onset of infection. ⁸ The aim of this study is to determine the frequency of abnormal ECG changes in patients with early LD seen in Stony Brook University Hospital (SBUH) which is the only major tertiary care medical center in Suffolk County, the area with the highest absolute number of LD cases reported in New York State.

A retrospective study was designed to identify cases of LD at SBUH between 2010–2016. SBUH is a 603-bed academic, tertiary medical center located in Suffolk County, Long Island, New York, USA. All patients with a discharge diagnosis of LD were identified by a search in the Electronic Medical Records (EMR) database of SBUH using International Classification of Diseases (ICD)-9 and ICD-10 codes. LD was defined either by the presence of EM rash, or two-tier serological confirmation by Western blot according to Center for Disease Control (CDC) criteria (at least two Immunoglobulin M [IgM] or five Immunoglobulin G [IgG] bands) and having being admitted to the hospital due to new diagnosis of LD. LC was defined as a case of LD with an abnormal ECG (AV block, right or left bundle branch abnormalities, new onset atrial fibrillation, T wave inversion, ST elevation and prolonged QT). Determination of LC was confirmed by either an infectious diseases specialist or a cardiologist. Demographics, past medical history, ECG and laboratory results were extracted from each patient’s chart. To identify risk factors, controls were included defined as LD with a normal ECG. Data were analyzed with STATA 12.1 (StataCorp, College Station, Texas, USA). This study was reviewed and approved by the Institutional Review Board (IRB# 834409) at SBUH.

Out of 767 patient charts reviewed, 247 met the inclusion criteria for new diagnosis of LD, 520 were excluded because they did not have a positive test for LD or had only a history of already treated LD. Of these 247 patients, 18 met the inclusion criteria for LC and 22 presented with a normal ECG and were included as the control group. The 18 LD patients with possible LC exhibited a median age of 44.5 years (range: 24–79), were predominantly male (78%) and Caucasian (83%). Of these 18 patients, one had EM with negative serology and the other 17 had 2–3 IgM specific bands for LD. Five presented with EM, 11 had five or more IgG bands. The most common symptoms at presentation were chest tightness, dizziness, and dyspnea on exertion and symptoms had been present for 4–30 days. Abnormal ECG findings included (total n = 18): AV block (2nd and 1st degree AV block (n = 4; 22.2%), right bundle branch conduction abnormalities (n = 6; 33.3%), new onset of atrial fibrillation (n = 2; 11.1%), T wave inversion (n = 3; 16.6%), sinus bradycardia with ST elevation (n = 1; 5.5%), prolonged QT interval (defined as ≥440 ms for men and ≥460 for women; n = 2; 11.1%). A summary of ECG findings is shown in Table 1. While eight patients demonstrated improvement in ECG changes, two had unchanged ECGs and eight did not have a repeat ECG. In the control group, the median age was 45.5 years (range: 26–75), 54.5% were male, and 81.8% Caucasians. Seven presented with EM (four with negative IgM, three had 2–3 bands of IgM), two had disseminated EM (2–3 bands of IgM), one had Bell’s palsy (two bands of IgM). Seven had five or more IgG bands. All had LD criteria based on CDC.

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Table 1.

Demographics, clinical features, laboratory and treatment outcomes on patients with Lyme carditis.

	Demographics		Symptoms		EKG Findings			Lyme serology
Patient	Age	Gender	Initial clinical symptoms	Recent EM	Prior normal/baseline EKG	Pre-treatment	Post-treatment	IgM immuno blot	IgG immuno blot
1	30	M	Chest pain, dizziness, SOB	No	No	Sinus tachycardia with Mobitz I (second degree AV block)	No change at day 9	23,39,41	18,23,28,39,41, 58,66,93
2	42	M	Arthralgia, chest pain, fever	Yes (disseminated)	No	Sinus rhythm with t-wave inversion	No change	23,39,41	18,23,39,41,66
3	47	F	Chest pain, dizziness, SOB	Yes	No	First degree heart block with inverted P wave	Two days after treatment changed to first degree AVB with shorter PR and QT interval and 3 years after: NSR, NL EKG	23,39,41	18,23,28,30,39,41, 45,58,66,93
4	33	M	Chest pain, dyspnea on exertion	No	No	Complete heart block	16 h after: changed to marked sinus brady with first degree AVB with incomplete RBBB,	23,39,41	23,28,39,41,58
5	40	F	Arthralgia, fatigue, fever, myalgia, pre-syncope, SOB	No	No	Accelerated junctional rhythm (no P-wave), incomplete RBBB went to first degree AV block to normal EKG in 3 days	One week after: normal EKG	23,41	18,28,39,41
6	24	M	Arthralgia, fatigue, fever	Yes (disseminated)	Sinus bradycardia with sinus arrhythmia in 2008. No block present.	AV II degree - Mobitz I	Three days after: I degree AV block	23,39,41	41,58
7	43	M	Chills, fatigue, fever, headache, N/V, pre-syncope	No	No	Incomplete RBBB	15 h later: resolved incomplete RBBB	39,41	18,41,93
8	79	M	Chills, facial paralysis, fever, rapid heart beat	Yes (disseminated)	Sinus tachycardia with A-V dissociation with occasional premature ectopic complexes in 2014	Atrial fibrillation with RVR	5 h after: EKG back to sinus rhythm with paroxysmal strial fibrillation	23,41	18,23,39,41,93
9	75	M	Dizziness, fatigue, fever, myalgia, SOB, weakness	Yes	Normal EKG 13 months prior.	New atrial fibrillation with RVR	No repeat EKG	23,39,41	18,23,39,41,45, 58,66,93
10	56	M	Epigastric pain, fever, radiculopathy	No	No	Incomplete RBBB	No repeat EKG	23,39,41	18,23,39,41,58,93
11	58	F	Chills, diarrhea, fatigue, fever, headache, knee pain, loss of appetite	No	No	Right bundle branch conductions abnormality	No repeat EKG	23,39,41	18,41,66,93
12	40	M	Eye tearing, facial droop, fatigue, fever, headache, myalgia, neck pain/stiffness	Yes	No	Sinus bradycardia with ST segment elevation	Two days later: EKG normal sinus rhythm	23,41	23,28,41,58,93
13	73	M	Anorexia (weight loss), chills, fatigue, fever, night sweats	Yes	No	Prolonged QT interval at 474 ms	No repeat EKG	23,41	23,39,41,5866
14	25	M	Fatigue, fever, night sweats, N/V	No	No	Inverted T wave in leads III, AVF and V6	No repeat EKG	23,39,41	41
15	46	F	Arthralgia, myalgia, nausea	Yes	No	Sinus tachycardia, rightward axis, right ventricular conduction delay, prolonged QT interval at 466 ms	No repeat EKG	negative	negative
16	69	M	Arthralgia, dizziness, fatigue, myalgia, upper extremity weakness	No	No	Incomplete RBBB	No repeat EKG	23,41	18,23,39,41, 45,58,93
17	60	M	Bell's palsy, facial numbness, fatigue, lock jaw, myalgia, stiff neck	No	Normal EKG 6 years prior	Frequent and consecutive premature ventricular complexes with occasional premature atrial complexes	4 h later: premature ventricular complex and atrial complex resolved	39,41	18,41,58,66,93
18	41	M	Chest pain, facial numbness, headache, wheezing	Yes	EKG 14 November 2013 showing left axis deviation	RSR or QR pattern in V1 suggests right ventricular conduction delay, LAFB	EKG three years later showed left axis deviation consistent with LAFB and slight intraventricular conduction delay	23,39,41	23,41

In the regression logistic model, antibiotics received prior to admission (odds ratio (OR) = 0.16, 95% confidence interval (CI): 0.02–0.96, p = 0.045) and arthralgia (OR = 4.74, 95% CI: 1.02–22.06; p = 0.047) were found to be statistically significantly associated with LC. The antibiotic regimen received before admission in the control group was a combination of cephalexin/bactrim (n = 3), doxycycline and cephalexin (n = 1), amoxicillin/clavulanic acid (n = 1), cephalexin alone (n = 1), levofloxacin (n = 2), and in the LC group was ciprofloxacin and doxycycline (n = 1), and ceftriaxone intravenously two days prior (n = 1). There was no mortality in either group. Also, the median number of days admitted to the hospital was significantly higher in the LC group compared to the control group (3 vs 0 days, p = 0.04).

Out of the 18 LC cases, nine had a localized or disseminated EM which correlates with the dissemination of the bacteria to other organs including the heart. However, half of them did not have a recent EM and their main complaints on presentation were shortness of breath, chest pain, or fatigue. While the severity of the infection, and the number of spirochetes present in the heart tissue may correlate with the occurrence of ECG abnormalities in humans, a strong correlation between degree of conduction disturbances, severity of cardiac inflammation, and the number of spirochetes in heart tissue was observed in non-human primates infected with B. burgdorferi; ⁹ which may be the reason why the prior use of antibiotics was less associated with LC in this study.

The findings of our study are important for several reasons. First, the description of ECG abnormalities in well-reported LD cases may help healthcare providers to suspect LD when a patient who lives in a hyperendemic LD area presents with unspecific ECG abnormalities. Second, the spectrum of ECG abnormalities in LC is unknown given the limited number of cases reported in the literature which are mostly complete AV blocks in need of a temporary pacemaker. Mild cases of LC may have not been reported due to several reasons including lack of ECG on presentation or mild symptoms that may not merit an ECG. Our study adds to the literature a greater spectrum of ECG abnormalities in LD which may be present in LC.

The spectrum of ECG abnormalities in LD may be broader than that previously suspected. Clinicians should be aware of these ECG abnormalities that may be a sign of LC in hyperendemic areas.