Autopsy Study of Sudden Cardiac Death & Lyme Carditis

Topics with information and discussion about published studies related to Lyme disease and other tick-borne diseases.
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RitaA
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Autopsy Study of Sudden Cardiac Death & Lyme Carditis

Post by RitaA » Sun 20 Mar 2016 6:03

http://www.ncbi.nlm.nih.gov/pubmed/26968341
Am J Pathol. 2016 Mar 8. pii: S0002-9440(16)00099-7. doi: 10.1016/j.ajpath.2015.12.027. [Epub ahead of print]

Cardiac Tropism of Borrelia burgdorferi: An Autopsy Study of Sudden Cardiac Death Associated with LymeCarditis.

Muehlenbachs A1, Bollweg BC2, Schulz TJ3, Forrester JD4, DeLeon Carnes M2, Molins C4, Ray GS3, Cummings PM5, Ritter JM2, Blau DM2, Andrew TA6, Prial M7, Ng DL2, Prahlow JA8, Sanders JH2, Shieh WJ2, Paddock CD9, Schriefer ME4, Mead P4, Zaki SR2.

Author information

1 Infectious Diseases Pathology Branch, Division of High Consequence Pathogens and Pathology, Centers for Disease Control and Prevention, Atlanta, Georgia.
2 Infectious Diseases Pathology Branch, Division of High Consequence Pathogens and Pathology, Centers for Disease Control and Prevention, Atlanta, Georgia.
3 CryoLife, Inc, Kennesaw, Georgia.
4 Bacterial Diseases Branch, Division of Vector Borne Infectious Diseases, Centers for Disease Control and Prevention, Ft. Collins, Colorado.
5 Office of the Chief Medical Examiner, Boston, Massachusetts.
6 Office of the Chief Medical Examiner, Concord, New Hampshire.
7 Office of the Medical Examiner, Goshen, New York.
8 The Medical Foundation, South Bend, Indiana; Indiana University School of Medicine-South Bend, South Bend, Indiana.
9 Rickettsial Zoonotic Diseases Branch, Division of Vector Borne Infectious Diseases, Atlanta, Georgia.

Abstract

Fatal Lyme carditis caused by the spirochete Borrelia burgdorferi rarely is identified. Here, we describe the pathologic, immunohistochemical, and molecular findings of five case patients. These sudden cardiac deaths associated with Lyme carditis occurred from late summer to fall, ages ranged from young adult to late 40s, and four patients were men. Autopsy tissue samples were evaluated by light microscopy, Warthin-Starry stain, immunohistochemistry, and PCR for B. burgdorferi, and immunohistochemistry for complement components C4d and C9, CD3, CD79a, and decorin. Post-mortem blood was tested by serology. Interstitial lymphocytic pancarditis in a relatively characteristic road map distribution was present in all cases. Cardiomyocyte necrosis was minimal, T cells outnumbered B cells, plasma cells were prominent, and mild fibrosis was present. Spirochetes in the cardiac interstitium associated with collagen fibers and co-localized with decorin. Rare spirochetes were seen in the leptomeninges of two cases by immunohistochemistry. Spirochetes were not seen in other organs examined, and joint tissue was not available for evaluation. Although rare, sudden cardiac death caused by Lyme disease might be an under-recognized entity and is characterized by pancarditis and marked tropism of spirochetes for cardiac tissues.

Published by Elsevier Inc.

PMID: 26968341 [PubMed - as supplied by publisher]

RitaA
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Re: Autopsy Study of Sudden Cardiac Death & Lyme Carditis

Post by RitaA » Sun 20 Mar 2016 6:16

http://rel-risk.blogspot.com/2016/03/th ... of-ld.html
Tuesday, March 15, 2016

The Heart of LD

Notes from:
Muehlenbachs A, et al. Cardiac Tropism of Borrelia burgdorferi: An Autopsy Study of Sudden Cardiac Death Associated with Lyme Carditis. Am J Pathol. 2016 Mar 8.

In the United States, cardiovascular symptoms occur in approximately 1.1% of reported cases, can manifest as conduction block, and, when recognized, usually resolve with appropriate antibiotics. Fatal myocarditis is rare, with only four cases reported before 2013 in the United States and Europe, including three cases with detailed pathology findings. In 2013, the CDC reported three additional cases of fatal carditis associated with Lyme disease.

B. burgdorferi possesses numerous adhesins that bind host extracellular matrix molecules, including glycosaminoglycans, fibronectin, collagen, and the small proteoglycan decorin, which mediate tissue tropism, pathogenicity, and immune invasion. In experimentally infected mice, B. burgdorferi binding to decorin has been implicated in spirochete cardiac tissue tropism.

…a major unanswered question is why sudden cardiac death during Lyme disease is so rare. The pathogenesis likely involves spirochete cardiac tissue tropism, and both host and spirochete factors may contribute to susceptibility. Although it is likely an underdiagnosed entity, under-diagnosis alone does not explain the disease rarity.

Lyme carditis occurs more frequently in men, and four of five sudden cardiac deaths described here, and the previously reported four, occurred in men. Sudden cardiac death in general occurs more frequently in men, and Wolf-Parkinson-White syndrome, a cardiac conduction system abnormality present in one of these patients, also is more common in men. A study in Slovenia found that although women present with predominantly cutaneous Lyme disease, men present with noncutaneous disease. The influence of sex on infectious disease is complex, and may involve differences in hormones, among other factors including behaviors associated with tick exposure. Of note, all patients also were than <50 years of age; Lyme carditis has been reported to be more common among men aged 20 to 39 years and women aged 25 to 29 years.

After myocardial injury, cardiac myocytes undergo cell necrosis and are replaced by scar composed of extracellular matrix. There is a delicate balance between extracellular matrix synthesis and degradation for optimum remodeling of scar tissue to obtain near pre-insult strength. Regulation of the fibroblast and myofibroblast response is performed in part by several extracellular matrix proteins. One of these proteins, decorin, is a ubiquitous proteoglycan associated with type I and type II collagen-rich tissues.

B. burgdorferi spirochetes adhere to the extracellular matrix during disseminated infection, and decorin plays a key role. Decorin-binding is mediated by B. burgdorferi decorin- binding proteins, in particular decorin-binding protein A, which is a 20-kDa surface protein. The dependence on decorin-binding for the spirochete to experimentally infect the heart is striking. Decorin-binding protein A is necessary for cardiac localization in a murine model, and, conversely, cardiac infection is diminished in decorin knock-out mice.

The differential diagnosis for acute myocarditis is broad and includes diverse viral, bacterial, and protozoal agents, including enteroviruses and human parvovirus B19, although often no etiologic pathogen can be identified by specialized studies. Post-infectious, post-inflammatory, auto-immune, or drug hypersensitivity phenomena also can cause mycoarditis. The histopathology of the inflammatory infiltrates in Lyme carditis is relatively characteristic. To increase awareness among pathologists and medical examiners, we would like to coin the term “road map” to describe the pattern of intersecting curvilinear bands of interstitial infiltrates seen on low-power magnification. Although this distribution of infiltrates is similar to that seen in hypersensitivity myocarditis, no granulomas, vasculitis, or significant eosinophilic infiltrates were seen in these Lyme carditis cases.

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ChronicLyme19
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Re: Autopsy Study of Sudden Cardiac Death & Lyme Carditis

Post by ChronicLyme19 » Tue 22 Mar 2016 3:49

Decorin-binding is mediated by B. burgdorferi decorin- binding proteins, in particular decorin-binding protein A, which is a 20-kDa surface protein.
So I wonder at what incidence people have this band test positive compared to the other bands...
Half of what you are taught is incorrect, but which half? What if there's another half missing?

dlf
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Re: Autopsy Study of Sudden Cardiac Death & Lyme Carditis

Post by dlf » Tue 22 Mar 2016 16:21

by ChronicLyme19 » Mon 21 Mar 2016 23:49

Decorin-binding is mediated by B. burgdorferi decorin- binding proteins, in particular decorin-binding protein A, which is a 20-kDa surface protein.


So I wonder at what incidence people have this band test positive compared to the other bands...
Likely either never because of the tests that are now in use, or if they are positive for a 20-kDa surface protein that appeared on a blot test it would not have been recorded. Many labs, like the Mayo clinic, have moved to an automated stripe type of Western blot testing. For example Mayo uses the Viramed Biotech AG-Borrelia B31 IgG ViraStripe, Viramed Biotech AG, Steinkirchen, Germany.

http://www.mayomedicallaboratories.com/ ... mance/9535
In the immunoblot analysis, an antigen mixture prepared from Borrelia burgdorferi strain B31 is separated by SDS-polyacrylamide gel electrophoresis (SDS-PAGE). After the antigens have been resolved by SDS-PAGE, they are electrophoretically transferred and bound to a nitrocellulose membrane. Patient specimen is then added to the nitrocellulose membrane.
Reactivity is only possible for the antigens included in these tests and is blocked for any antigens that are not included in the test strips.

Bear in mind that an IgG Western Blot must have five or more of these bands: 18, 23,28, 30, 39, 41, 45, 58, 66, and 93 kDa. An IgM Western Blot must have two or more bands of the following three bands: 23, 39, 41. These stripe tests do not have any possible way to register a positive result at 20 kDa!

http://www.viramed.de/en/component/cont ... virastripe

Some of the older blot tests could pick up the signal from other proteins that react, like the 20kDa band, but because those are not considered significant for serology testing to determine whether the results are positive or not, that band would not be recorded anywhere except on the test strip itself. It would never be reported in test results.

A good reference for these things is:

Binnicker MJ, Jespersen DJ, Harring JA, Rollins LO, Bryant SC, Beito EM. Evaluation of Two Commercial Systems for Automated Processing, Reading, and Interpretation of Lyme Borreliosis Western Blots . Journal of Clinical Microbiology. 2008;46(7):2216-2221. doi:10.1128/JCM.00200-08.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2446909/

In this article they have a visual example of how this works. It shows a comparison of WB strips for a single patient specimen. The same patient specimen was tested by the MarBlot, ViraBlot, and ViraStripe assays. Strips were scanned by their respective systems, and the images were captured in tag image file format (TIFF). The migration positions of bands used in the CDC interpretation criteria are indicated by molecular mass (in kilodaltons). PC, positive control; T, test (patient) sample.

http://www.ncbi.nlm.nih.gov/pmc/article ... 110002.jpg

In the Relative Risk blog that RitaA posted, it was noted that, "all patients also were <50 years of age; Lyme carditis has been reported to be more common among men aged 20 to 39 years and women aged 25 to 29 years."

Similar to the reason Lyme disease was first recognized in the 1970s, because the symptoms were appearing in young people who would have had no simple and ready explanation for these symptoms under normal conditions, I suspect Lyme carditis is only noted in younger people because older folks would be expected to have cardiac arrest as a result of more usual risk factors related to being over 50, so it wouldn't even be looked for in older people. The old, "Don't look, don't see" principle at work.

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ChronicLyme19
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Re: Autopsy Study of Sudden Cardiac Death & Lyme Carditis

Post by ChronicLyme19 » Wed 23 Mar 2016 2:24

dlf wrote:Bear in mind that an IgG Western Blot must have five or more of these bands: 18, 23,28, 30, 39, 41, 45, 58, 66, and 93 kDa. An IgM Western Blot must have two or more bands of the following three bands: 23, 39, 41. These stripe tests do not have any possible way to register a positive result at 20 kDa!
Ah, right right, thanks for the reminder.
Half of what you are taught is incorrect, but which half? What if there's another half missing?

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