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Lyme Carditis and High-Degree Atrioventricular Block
Accepted Manuscript Title: Lyme Carditis and High-Degree Atrioventricular Block Author: Douglas Wan, Crystal Blakely, Pamela Branscombe, Laiden SuarezFuster, Benedict Glover, Adrian Baranchuk PII: DOI: Reference:
S0002-9149(18)30168-1 https://doi.org/10.1016/j.amjcard.2018.01.026 AJC 23104
To appear in:
The American Journal of Cardiology
Received date: Accepted date:
9-11-2017 9-1-2018
Please cite this article as: Douglas Wan, Crystal Blakely, Pamela Branscombe, Laiden SuarezFuster, Benedict Glover, Adrian Baranchuk, Lyme Carditis and High-Degree Atrioventricular Block, The American Journal of Cardiology (2018), https://doi.org/10.1016/j.amjcard.2018.01.026. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Lyme Carditis and High-degree Atrioventricular Block
Douglas Wan MD, Crystal Blakely RN, Pamela Branscombe RN, Laiden Suarez-Fuster MD, Benedict Glover MD, Adrian Baranchuk MD
Department of Medicine, Division of Cardiology, Queen’s University, Kingston, Ontario, Canada
Running title: Lyme Carditis & High-degree AV Block Word count: 1139 Abstract word count: 73 Disclosures: None. Address for Correspondence: Adrian Baranchuk, MD Professor of Medicine Cardiac Electrophysiology and Pacing; Kingston General Hospital K7L 2V7 Queen's University Ph: 613 549 6666 ext 3377 Fax: 613 548 1387 Email: [email protected]
1 Page 1 of 10
Abstract Canada has seen a 6-fold increase in Lyme disease (LD) since being nationally notifiable in 2009. This is the first Canadian series on Lyme carditis manifested as high-degree atrioventricular block. We report 5 recent cases presented over a 2-year period. The variation of non-specific presentations requires a high index of suspicion for prompt diagnosis and correct management. Recognising this early would curtail the progression of conduction disorders and potentially avoid permanent pacemaker implantation. Key words: Lyme Carditis; High-degree AV Block; ECG; temporary pacemaker
2 Page 2 of 10
Introduction The discovery of Borrelia burgdorferi as the cause of Lyme disease (LD) was published in 1982 [1]. Geographically prevalent areas of this tick vector have expanded along the Canadian border shared with United States [1-2]. LD became nationally (Canada) notifiable in 2009. Since then, its incidence in Canada has increased 6-fold [2]. Compared to skin, joint and neurological manifestations, cardiac involvement is the least reported. The incidence of cardiac involvement in LD has historically been as high as 10% in earlier studies, but more recent studies have reported incidences between 0.3 - 4% [3]. Lyme carditis is one of the features of early disseminated LD, usually occurring in the first few weeks. The cardiac conduction system is frequently involved in Lyme carditis; however, the myocardium and pericardium can be also involved [3]. In this case series, we describe the clinical presentation, evaluation and management of patients with Lyme carditis presenting with high-degree atrioventricular block (AVB). Single-center, case series observational study over a 2-year period in an academic hospital (Kingston General Hospital, Kingston, Ontario, Canada). Data collection included demographic information, clinical characteristics, surface electrocardiography, echocardiography (if available), stress test prior to discharge and management. Results A total of 5 serological (positive ELISA and Western Blot) confirmed cases of Lyme carditis presenting with high-degree AVB were included in the analysis. All of them were males, younger than 35 years of age. Some commonalities are worth to mention: they were all exposed to outdoor activities in an established endemic region; however, only 3 of them remembered a “tick-bite”. Only 1 of them presented Erythema Migrans (EM), a skin lesion characteristic of
3 Page 3 of 10
LD. All of them presented some form of constitutional symptoms such as fatigue, fever, headache, neck stiffness, flu-like symptoms, nausea, arthralgia, and/or myalgia. Only 1 patient presented left facial nerve palsy. It was common for patients to attend the emergency department more than once until the diagnosis was suspected. Three patients presented complete AVB while the other 2 developed second-degree atrioventricular block with 2:1 conduction. Figure 1 shows the ECG of patients #1, #2 and #4, respectively. All patients were treated with antibiotics (4 patients received intravenous Ceftriaxone and one patient oral Doxycyclyne) and no patient required permanent pacing (Table 1). Temporary pacing was indicated according to hemodynamic tolerance to bradycardia. Figure 2 shows the electrocardiographic progression of patient #3, with 1:1 conduction recovery after 10 days of antibiotic treatment. Echocardiograms were performed showing alterations in 2 patients: one mild right ventricular dilation and one focal myocarditis and diastolic dysfunction. Constitutional symptoms resolved during the admission. All patients underwent a treadmill test before discharge to assess atrioventricular conduction. Intravenous Ceftriaxone was converted to oral antibiotics either before or after discharge, but exclusively after 24-48 hours resolution of high-degree AVB. During the followup, no conduction abnormalities were detected. Discussion We report five cases of Lyme carditis manifesting with high-degree AV block. All these cases presented over a relatively short period of time. The South Eastern region of Ontario is an endemic area for high tick species Ixodes scapularis, which is a vector for Borrelia burgdorferi [2]. The demographics of this case series is reflective of the age group (teenagers and middleage) and male preponderance in Lyme carditis patients reported in literature [3,4]. Although some patients will recall environmental exposure, a recognized tick bite is often not noticed.
4 Page 4 of 10
This series of Lyme carditis patients correlates well with the spread of clinical presentations, with skin and neurological involvement (Table 1). EM is pathognomonic of LD and is reported to be present in 70-90% of cases.[1,4] However, EM is less common in Lyme carditis (40%) [3]. It may be because EM occurs early in the disease, that it is not often seen by the time patients present with cardiac features. The absence of pathognomonic EM, presentation with non-specific symptoms and involvement of various systems, all can potentially distract a physician from making the correct diagnosis at initial presentation. Conduction disorders include varying degrees of AVB, but also sinus node disease, interventricular delay, and prolonged QT interval [3,4]. All cases in this series presented highdegree AVB during the hospital visit that clinched the diagnosis of LD. Given the potentially rapid progressive nature of LD, all patients with suspected LD should be evaluated with a 12lead ECG and be on cardiac monitoring whist treatment is initiated [5]. About a third of Lyme carditis patients may require temporary pacing [5]. In our series, two of the five patients required temporary pacing because of hemodynamic compromise associated with their bradycardia (Table 1). Due to the transient nature of LD affecting the conduction system, permanent damage requiring pacing is exceedingly rare [4]. None of our patients required a permanent pacemaker. Stability of the atrioventricular conduction was tested with a stress test prior to discharge and confirmed by follow-up once the antibiotic treatment was completed. Antibiotics is the mainstay treatment that can reliably and completely reverse AVB if started early in the disease process. Published recommendations state antibiotic duration should be between 2-4 weeks. Some recommendations vary in antibiotic choice based on the degree of AVB [1,3-4]. This underpins the pivotal role of prompt diagnosis. All our patients had resolution
5 Page 5 of 10
of the high-degree AVB within 1-2 weeks (average 5 days) of starting antibiotics. This recovery time is consistent with published literature. Cardiac involvement may be the first and sole manifestation of LD. Without considering LD as a reversible cause, it might result in an unnecessary permanent pacemaker implantation. [1,4] Furthermore, there is some evidence that recovery is permanent, suggesting long-term follow-up after complete resolution of AVB may not be necessary. Our final observation of this case series is that it is not uncommon for patients to present several times before the clinical diagnosis is made and appropriate treatment commenced. This is important due to the potentially rapidly progressive nature of AVB. The increasing spread of tick vectors for LD merits greater consideration in this reversible cause of severe conduction disorders. Therefore, we propose that LD should be considered in all young individuals (with a male preponderance), who have no apparent cause of AVB before implanting a pacemaker. The correct diagnosis may save patients from the inherent risks of pacemaker implantation, possible late complications, a lifetime of multiple pulse generator changes, and the burden of associated cumulative health care costs. This report is a small series based on a single centre experience. Further studies into Lyme carditis manifesting as significant conduction disorders would benefit from a multi-centered approach. In conclusion, this case series suggests that the prevalence of Lyme carditis may be higher than previously seen. A high index of suspicion is required due to the variable and non-specific presentations, particularly in endemic areas. Prompt diagnosis and early treatment with antibiotics curtails the progression of conduction disorders cause by Lyme carditis and avoid the rarely needed possibility of permanent pacemaker implantation.
6 Page 6 of 10
1. Ogden NH, Lindsay LR, Morshed M, Sockett PN, Artsob H.
The emergence of Lyme
disease in Canada. CMAJ. 2009;180(12):1221-1224 2. Public Health Notice on Lyme Disease 2009-2016. Ottawa: Public Health Agency of Canada; 2017. Available: https://www.canada.ca/en/public-health/services/diseases/lymedisease/surveillance-lyme-disease.html (accessed 2017 September 18) 3. Krause PJ, Bockenstedt LK. Lyme disease and the heart. Circulation. 2013;127(7):e451-e454 4. Nagi KS, Joshi R, Thakur RK. Cardiac manifestations of Lyme disease: a review. Can J Cardiol. 1996;12(5):503-506 5. Fuster LS, Gul EE, Baranchuk A. Electrocardiographic progression of acute Lyme disease. Am J Emerg Med. 2017;35(7):1040.e5-1040.e6.
Legends to the Figures and Table
Figure 1: ECG manifestations of three different cases. A: Case #1, B: Case #2 and C: Case #4. Figure 2: Electrocardiographic progression of Case #3 (adapted from reference #5)
7 Page 7 of 10
Table 1: Findings in 5 males with symptomatic Lyme disease and positive Lyme serology. 1
2
3
4
5
Age (years)
23
35
30
14
19
Recognized tick bite
Y
N
Y
N
Y
Erythema migrans
N
N
N
Y
N
Lyme suspected on visit #
4th
1st
2st
2nd
1st
Atrioventricular block
3°
3°
3°
2°
2°
Temporary pacing wire
N
Y
Y
N
N
High degree AVB resolution (days)
5d
3d
10d
6d
2d
8 Page 8 of 10
Figure 1.jpg
9 Page 9 of 10
Figure 2.JPG
10 Page 10 of 10
S0002-9149(18)30168-1 https://doi.org/10.1016/j.amjcard.2018.01.026 AJC 23104
To appear in:
The American Journal of Cardiology
Received date: Accepted date:
9-11-2017 9-1-2018
Please cite this article as: Douglas Wan, Crystal Blakely, Pamela Branscombe, Laiden SuarezFuster, Benedict Glover, Adrian Baranchuk, Lyme Carditis and High-Degree Atrioventricular Block, The American Journal of Cardiology (2018), https://doi.org/10.1016/j.amjcard.2018.01.026. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Lyme Carditis and High-degree Atrioventricular Block
Douglas Wan MD, Crystal Blakely RN, Pamela Branscombe RN, Laiden Suarez-Fuster MD, Benedict Glover MD, Adrian Baranchuk MD
Department of Medicine, Division of Cardiology, Queen’s University, Kingston, Ontario, Canada
Running title: Lyme Carditis & High-degree AV Block Word count: 1139 Abstract word count: 73 Disclosures: None. Address for Correspondence: Adrian Baranchuk, MD Professor of Medicine Cardiac Electrophysiology and Pacing; Kingston General Hospital K7L 2V7 Queen's University Ph: 613 549 6666 ext 3377 Fax: 613 548 1387 Email: [email protected]
1 Page 1 of 10
Abstract Canada has seen a 6-fold increase in Lyme disease (LD) since being nationally notifiable in 2009. This is the first Canadian series on Lyme carditis manifested as high-degree atrioventricular block. We report 5 recent cases presented over a 2-year period. The variation of non-specific presentations requires a high index of suspicion for prompt diagnosis and correct management. Recognising this early would curtail the progression of conduction disorders and potentially avoid permanent pacemaker implantation. Key words: Lyme Carditis; High-degree AV Block; ECG; temporary pacemaker
2 Page 2 of 10
Introduction The discovery of Borrelia burgdorferi as the cause of Lyme disease (LD) was published in 1982 [1]. Geographically prevalent areas of this tick vector have expanded along the Canadian border shared with United States [1-2]. LD became nationally (Canada) notifiable in 2009. Since then, its incidence in Canada has increased 6-fold [2]. Compared to skin, joint and neurological manifestations, cardiac involvement is the least reported. The incidence of cardiac involvement in LD has historically been as high as 10% in earlier studies, but more recent studies have reported incidences between 0.3 - 4% [3]. Lyme carditis is one of the features of early disseminated LD, usually occurring in the first few weeks. The cardiac conduction system is frequently involved in Lyme carditis; however, the myocardium and pericardium can be also involved [3]. In this case series, we describe the clinical presentation, evaluation and management of patients with Lyme carditis presenting with high-degree atrioventricular block (AVB). Single-center, case series observational study over a 2-year period in an academic hospital (Kingston General Hospital, Kingston, Ontario, Canada). Data collection included demographic information, clinical characteristics, surface electrocardiography, echocardiography (if available), stress test prior to discharge and management. Results A total of 5 serological (positive ELISA and Western Blot) confirmed cases of Lyme carditis presenting with high-degree AVB were included in the analysis. All of them were males, younger than 35 years of age. Some commonalities are worth to mention: they were all exposed to outdoor activities in an established endemic region; however, only 3 of them remembered a “tick-bite”. Only 1 of them presented Erythema Migrans (EM), a skin lesion characteristic of
3 Page 3 of 10
LD. All of them presented some form of constitutional symptoms such as fatigue, fever, headache, neck stiffness, flu-like symptoms, nausea, arthralgia, and/or myalgia. Only 1 patient presented left facial nerve palsy. It was common for patients to attend the emergency department more than once until the diagnosis was suspected. Three patients presented complete AVB while the other 2 developed second-degree atrioventricular block with 2:1 conduction. Figure 1 shows the ECG of patients #1, #2 and #4, respectively. All patients were treated with antibiotics (4 patients received intravenous Ceftriaxone and one patient oral Doxycyclyne) and no patient required permanent pacing (Table 1). Temporary pacing was indicated according to hemodynamic tolerance to bradycardia. Figure 2 shows the electrocardiographic progression of patient #3, with 1:1 conduction recovery after 10 days of antibiotic treatment. Echocardiograms were performed showing alterations in 2 patients: one mild right ventricular dilation and one focal myocarditis and diastolic dysfunction. Constitutional symptoms resolved during the admission. All patients underwent a treadmill test before discharge to assess atrioventricular conduction. Intravenous Ceftriaxone was converted to oral antibiotics either before or after discharge, but exclusively after 24-48 hours resolution of high-degree AVB. During the followup, no conduction abnormalities were detected. Discussion We report five cases of Lyme carditis manifesting with high-degree AV block. All these cases presented over a relatively short period of time. The South Eastern region of Ontario is an endemic area for high tick species Ixodes scapularis, which is a vector for Borrelia burgdorferi [2]. The demographics of this case series is reflective of the age group (teenagers and middleage) and male preponderance in Lyme carditis patients reported in literature [3,4]. Although some patients will recall environmental exposure, a recognized tick bite is often not noticed.
4 Page 4 of 10
This series of Lyme carditis patients correlates well with the spread of clinical presentations, with skin and neurological involvement (Table 1). EM is pathognomonic of LD and is reported to be present in 70-90% of cases.[1,4] However, EM is less common in Lyme carditis (40%) [3]. It may be because EM occurs early in the disease, that it is not often seen by the time patients present with cardiac features. The absence of pathognomonic EM, presentation with non-specific symptoms and involvement of various systems, all can potentially distract a physician from making the correct diagnosis at initial presentation. Conduction disorders include varying degrees of AVB, but also sinus node disease, interventricular delay, and prolonged QT interval [3,4]. All cases in this series presented highdegree AVB during the hospital visit that clinched the diagnosis of LD. Given the potentially rapid progressive nature of LD, all patients with suspected LD should be evaluated with a 12lead ECG and be on cardiac monitoring whist treatment is initiated [5]. About a third of Lyme carditis patients may require temporary pacing [5]. In our series, two of the five patients required temporary pacing because of hemodynamic compromise associated with their bradycardia (Table 1). Due to the transient nature of LD affecting the conduction system, permanent damage requiring pacing is exceedingly rare [4]. None of our patients required a permanent pacemaker. Stability of the atrioventricular conduction was tested with a stress test prior to discharge and confirmed by follow-up once the antibiotic treatment was completed. Antibiotics is the mainstay treatment that can reliably and completely reverse AVB if started early in the disease process. Published recommendations state antibiotic duration should be between 2-4 weeks. Some recommendations vary in antibiotic choice based on the degree of AVB [1,3-4]. This underpins the pivotal role of prompt diagnosis. All our patients had resolution
5 Page 5 of 10
of the high-degree AVB within 1-2 weeks (average 5 days) of starting antibiotics. This recovery time is consistent with published literature. Cardiac involvement may be the first and sole manifestation of LD. Without considering LD as a reversible cause, it might result in an unnecessary permanent pacemaker implantation. [1,4] Furthermore, there is some evidence that recovery is permanent, suggesting long-term follow-up after complete resolution of AVB may not be necessary. Our final observation of this case series is that it is not uncommon for patients to present several times before the clinical diagnosis is made and appropriate treatment commenced. This is important due to the potentially rapidly progressive nature of AVB. The increasing spread of tick vectors for LD merits greater consideration in this reversible cause of severe conduction disorders. Therefore, we propose that LD should be considered in all young individuals (with a male preponderance), who have no apparent cause of AVB before implanting a pacemaker. The correct diagnosis may save patients from the inherent risks of pacemaker implantation, possible late complications, a lifetime of multiple pulse generator changes, and the burden of associated cumulative health care costs. This report is a small series based on a single centre experience. Further studies into Lyme carditis manifesting as significant conduction disorders would benefit from a multi-centered approach. In conclusion, this case series suggests that the prevalence of Lyme carditis may be higher than previously seen. A high index of suspicion is required due to the variable and non-specific presentations, particularly in endemic areas. Prompt diagnosis and early treatment with antibiotics curtails the progression of conduction disorders cause by Lyme carditis and avoid the rarely needed possibility of permanent pacemaker implantation.
6 Page 6 of 10
1. Ogden NH, Lindsay LR, Morshed M, Sockett PN, Artsob H.
The emergence of Lyme
disease in Canada. CMAJ. 2009;180(12):1221-1224 2. Public Health Notice on Lyme Disease 2009-2016. Ottawa: Public Health Agency of Canada; 2017. Available: https://www.canada.ca/en/public-health/services/diseases/lymedisease/surveillance-lyme-disease.html (accessed 2017 September 18) 3. Krause PJ, Bockenstedt LK. Lyme disease and the heart. Circulation. 2013;127(7):e451-e454 4. Nagi KS, Joshi R, Thakur RK. Cardiac manifestations of Lyme disease: a review. Can J Cardiol. 1996;12(5):503-506 5. Fuster LS, Gul EE, Baranchuk A. Electrocardiographic progression of acute Lyme disease. Am J Emerg Med. 2017;35(7):1040.e5-1040.e6.
Legends to the Figures and Table
Figure 1: ECG manifestations of three different cases. A: Case #1, B: Case #2 and C: Case #4. Figure 2: Electrocardiographic progression of Case #3 (adapted from reference #5)
7 Page 7 of 10
Table 1: Findings in 5 males with symptomatic Lyme disease and positive Lyme serology. 1
2
3
4
5
Age (years)
23
35
30
14
19
Recognized tick bite
Y
N
Y
N
Y
Erythema migrans
N
N
N
Y
N
Lyme suspected on visit #
4th
1st
2st
2nd
1st
Atrioventricular block
3°
3°
3°
2°
2°
Temporary pacing wire
N
Y
Y
N
N
High degree AVB resolution (days)
5d
3d
10d
6d
2d
8 Page 8 of 10
Figure 1.jpg
9 Page 9 of 10
Figure 2.JPG
10 Page 10 of 10