Accepted Manuscript Tropheryma whipplei endocarditis: the value of valve polymerase chain reaction in cardiac surgery David Rose , Achyut Guleri , Augustine Tang PII:
S0022-5223(14)00589-3
DOI:
10.1016/j.jtcvs.2014.05.045
Reference:
YMTC 8632
To appear in:
The Journal of Thoracic and Cardiovascular Surgery
Received Date: 4 April 2014 Revised Date:
11 May 2014
Accepted Date: 14 May 2014
Please cite this article as: Rose D, Guleri A, Tang A, Tropheryma whipplei endocarditis: the value of valve polymerase chain reaction in cardiac surgery, The Journal of Thoracic and Cardiovascular Surgery (2014), doi: 10.1016/j.jtcvs.2014.05.045. 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.
ACCEPTED MANUSCRIPT TITLE Tropheryma whipplei endocarditis: the value of valve polymerase chain reaction in cardiac surgery.
RI PT
AUTHORS
SC
David Rose1, Achyut Guleri2, Augustine Tang1, 3
1. Lancashire Cardiac Centre, Blackpool, Lancashire, FY3 8NR UK
M AN U
2. Clinical Microbiology, Blackpool, Lancashire, FY3 8NR UK
TE D
3. School of Health & Medicine, Lancaster University, Bailrigg, Lancashire, LA1 4YA UK
Corresponding author
David Rose, Lancashire Cardiac Centre, Whinney Heys Road, Blackpool, Lancashire FY3 8NR, UK.
AC C
Keywords
EP
[email protected]; Tel 00393207260389
Tropheryma whipplei disease; infective endocarditis; CRP.
Word count 779
ACCEPTED MANUSCRIPT Introduction Tropheryma whipplei is the etiologic agent of Whipple’s disease, a chronic infection characterized by diarrhea, weight loss, intra-abdominal lymphadenopathy, and arthropathy. The disease is extremely rare with an estimated incidence of below 1/1,000,000, and the cardiac involvement has been
RI PT
reported in 17 to 55% of patients with classical Whipple's disease, pericarditis being the most frequent. We report a case of a patient with a very rare Tropheryma whipplei pancarditis in whom the cardiac involvement characterized the initial presentation without any intestinal symptoms. Isolate
SC
identification was confirmed by DNA nucleotide sequencing of explanted valve tissue in response to a high index of suspicion of an infectious process arising from intraoperative findings despite negative
M AN U
results of routine cultures.
CASE REPORT
A previously fit and active 71-year-old man presented with NSTEMI (Non ST segment Myocardial
TE D
Infarction) and respiratory failure needing ventilation in Intensive Care Unit. Transthoracic echocardiography revealed severe aortic regurgitation and severe mitral regurgitation. The noncoronary aortic cusp and adjacent annulus appeared thickened with restricted movement. (Figure 1.
EP
Panel A – Video 1). The posterior mitral valve leaflet was thickened at the base with further nodular thickening of the anterior leaflet (Figure 1. Panel B.). Coronary angiogram showed severe triple vessel
AC C
disease. Left ventricular ejection fraction was 45%. Intraoperatively the pericardial space was found to be filled with unusually dense adhesions with multiple calcified nodules scattered across the epicardium (Figure 1. Panel C). After cardioplegic arrest and triple bypass grafting, the aortic root was inspected showing the non-coronary cusp entirely destroyed adjacent to the abscess (Figure 1 Panel D). The annular tissue was grossly thickened and fibrosed. After deroofing the abscess greyish pus was evacuated (supplementary pictures). Following debridement the cavity walls were plicated to eliminate the space. Gross thickening was found in both, mitral leaflets and subchordal apparatus in addition to two separate chronic abscess cavities along the posterior annulus (Figure 1 Panel E). After
ACCEPTED MANUSCRIPT debridement and annular reconstruction using a tailored pericardial patch, a bioprosthesis was implanted with papillary muscle resuspension. Routine cultures of valve specimens resulted negative. Histopathology showed focal myxoid degeneration with fragments of partially hyalinised fibrous connective tissue and extensive amorphous dystrophic calcification accompanied by chronic
RI PT
inflammation including histiocytes, macrophages, neutrophils and plasma cells (Figure 1 Panel F). Identification of Tropheryma whipplei was confirmed using DNA amplification technique (polymerase chain reaction) plus sequencing. This enabled optimisation of post-operative treatment
SC
with oral Co-trimoxazole 960 mg (trimetoprim-sulfametoxazol) after surgery for 12 months. The postoperative course was uneventful at 8-month follow-up with no echocardiographic or clinical evidence
M AN U
of recurrent infection.
DISCUSSION
Whipple’s disease is a rare condition first described by George Hoyt Whipple in 1907, caused by
TE D
Tropheryma whippley. This organism belongs to the Gram-positive actinomycetes and some studies have shown a statistically significantly higher prevalence in farming profession over persons with other occupations. It usually presents with gastrointestinal symptoms whilst affecting the
EP
cardiovascular system to a lesser extent1. The disease is extremely rare with an estimated incidence of below 1/1,000,000. It is strongly prevalent in Caucasian males with a male to female ratio of 8:1, and
AC C
a mean age of onset around 50 years.2 Cardiac involvement has been reported in 17 to 55% of patients with classical Whipple's disease with pericarditis being the most common3. It is very rare that cardiac involvement is the primary and sole presentation in absence of intestinal symptoms. Tropheryma whipplei IE (infective endocarditis) is difficult to diagnose because blood cultures often fail to reveal the organism, resulting in up to 31% of culture-negative cases4. Thus molecular method for the identification of Tropheryma whipplei is an important tool for the management of the uncommon forms of infective endocarditis. Immunohistochemical analysis for T whipplei remains the gold standard for the diagnosis of Whipple disease. It is a sensitive and specific method that can be
ACCEPTED MANUSCRIPT easily performed in most laboratories5. This method offers added specificity over PCR methods owing to the direct visualization of bacilli and antigens within cells in tissue sections and offers increased sensitivity and specificity over the traditional PAS staining method. However the systematic use of PCR amplification of the bacterial 16 rRNA gene, and subsequent sequencing in valvular tissue is
RI PT
increasing the percentage of patients diagnosed with Tropheryma whipplei endocarditis4. The correct diagnosis of Tropheryma whipplei infection is critical because it guides postoperative antimicrobial treatment in the prevention of recurrent endocarditis. The latter occurs commonly without prolonged antibiotic treatment, is then hard to eradicate and reoperations carry substantial morbidity and
SC
mortality.
M AN U
In conclusion, PCR adds substantially to the etiologic diagnosis of IE, leading to institution of appropriate antibiotic therapy. It should be considered in all cases in which routine cultures are negative despite a high index of clinical suspicion of IE.
TE D
Figure Legend Figure 1
EP
Panel A. Detail of the non-coronary aortic cusp appearing thickened (White arrow). Panel B. Mitral valve with the posterior leaflet thickened at the base (white arrow) with further nodular thickening of
AC C
the anterior leaflet (tip of white arrow). Panel C. Intraoperative aspect of the pericardium presenting with multiple calcified nodules scattered across the epicardium. Panel D. Intraoperative aspect of the aortic valve with the non-coronary cusp entirely destroyed adjacent to the abscess (black arrow). Panel E. Intraoperative aspect of the mitral valve presenting with a gross thickening in both mitral leaflets (hash, anterior leaflet; asterisk, posterior leaflet). Panel F. Histological evaluation showing focal myxoid degeneration with fragments of partially hyalinised fibrous connective tissue and extensive amorphous dystrophic calcification accompanied by chronic inflammation including histiocytes, macrophages, neutrophils and plasma cells.
ACCEPTED MANUSCRIPT
REFERENCES 1. Fenollar F, Puéchal X, Raoult D: Whipple's disease. New Eng J Med 2007, 356:55-66.
RI PT
2. Fenollar F, Célard M, Lagier JC, Lepidi H, Fournier PE, Raoult D. Tropheryma whipplei endocarditis.. Emerg Infect Dis 2013;19:1721-30
3. Amendolara M, Barbarino C, Bucca D, Stevanato G, Zucchelli M, Romano F, Baiano L,
SC
Bernardi M, Broggiato A, Ramuscello S, Rizzo M. Whipple's disease infection surgical treatment: presentation of a rare case and literature review. G Chir. 2013 Apr;34:117-21.
M AN U
4. Geissdörfer W, Moos V, Moter A, Loddenkemper C, Jansen A, Tandler R, Morguet AJ, Fenollar F, Raoult D, Bogdan C, Schneider T. High frequency of Tropheryma Whippley in culture negative endocarditis J Clin Microbiol. 2012 Feb;50:216-22. 5. Baisden BL, Lepidi H, Raoult D, Argani P, Yardley JH, Dumler JS. Diagnosis of Wihipple
TE D
disease by immunohistochemical analysis: a sensitive and specific method for the detection of Tropheryma whipplei (the Whipple bacillus) in paraffin-embedded tissue. Am J Clin Pathol.
AC C
EP
2002 Nov;118:742-8.
AC C
EP
TE D
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT
S0022-5223(14)00589-3
DOI:
10.1016/j.jtcvs.2014.05.045
Reference:
YMTC 8632
To appear in:
The Journal of Thoracic and Cardiovascular Surgery
Received Date: 4 April 2014 Revised Date:
11 May 2014
Accepted Date: 14 May 2014
Please cite this article as: Rose D, Guleri A, Tang A, Tropheryma whipplei endocarditis: the value of valve polymerase chain reaction in cardiac surgery, The Journal of Thoracic and Cardiovascular Surgery (2014), doi: 10.1016/j.jtcvs.2014.05.045. 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.
ACCEPTED MANUSCRIPT TITLE Tropheryma whipplei endocarditis: the value of valve polymerase chain reaction in cardiac surgery.
RI PT
AUTHORS
SC
David Rose1, Achyut Guleri2, Augustine Tang1, 3
1. Lancashire Cardiac Centre, Blackpool, Lancashire, FY3 8NR UK
M AN U
2. Clinical Microbiology, Blackpool, Lancashire, FY3 8NR UK
TE D
3. School of Health & Medicine, Lancaster University, Bailrigg, Lancashire, LA1 4YA UK
Corresponding author
David Rose, Lancashire Cardiac Centre, Whinney Heys Road, Blackpool, Lancashire FY3 8NR, UK.
AC C
Keywords
EP
[email protected]; Tel 00393207260389
Tropheryma whipplei disease; infective endocarditis; CRP.
Word count 779
ACCEPTED MANUSCRIPT Introduction Tropheryma whipplei is the etiologic agent of Whipple’s disease, a chronic infection characterized by diarrhea, weight loss, intra-abdominal lymphadenopathy, and arthropathy. The disease is extremely rare with an estimated incidence of below 1/1,000,000, and the cardiac involvement has been
RI PT
reported in 17 to 55% of patients with classical Whipple's disease, pericarditis being the most frequent. We report a case of a patient with a very rare Tropheryma whipplei pancarditis in whom the cardiac involvement characterized the initial presentation without any intestinal symptoms. Isolate
SC
identification was confirmed by DNA nucleotide sequencing of explanted valve tissue in response to a high index of suspicion of an infectious process arising from intraoperative findings despite negative
M AN U
results of routine cultures.
CASE REPORT
A previously fit and active 71-year-old man presented with NSTEMI (Non ST segment Myocardial
TE D
Infarction) and respiratory failure needing ventilation in Intensive Care Unit. Transthoracic echocardiography revealed severe aortic regurgitation and severe mitral regurgitation. The noncoronary aortic cusp and adjacent annulus appeared thickened with restricted movement. (Figure 1.
EP
Panel A – Video 1). The posterior mitral valve leaflet was thickened at the base with further nodular thickening of the anterior leaflet (Figure 1. Panel B.). Coronary angiogram showed severe triple vessel
AC C
disease. Left ventricular ejection fraction was 45%. Intraoperatively the pericardial space was found to be filled with unusually dense adhesions with multiple calcified nodules scattered across the epicardium (Figure 1. Panel C). After cardioplegic arrest and triple bypass grafting, the aortic root was inspected showing the non-coronary cusp entirely destroyed adjacent to the abscess (Figure 1 Panel D). The annular tissue was grossly thickened and fibrosed. After deroofing the abscess greyish pus was evacuated (supplementary pictures). Following debridement the cavity walls were plicated to eliminate the space. Gross thickening was found in both, mitral leaflets and subchordal apparatus in addition to two separate chronic abscess cavities along the posterior annulus (Figure 1 Panel E). After
ACCEPTED MANUSCRIPT debridement and annular reconstruction using a tailored pericardial patch, a bioprosthesis was implanted with papillary muscle resuspension. Routine cultures of valve specimens resulted negative. Histopathology showed focal myxoid degeneration with fragments of partially hyalinised fibrous connective tissue and extensive amorphous dystrophic calcification accompanied by chronic
RI PT
inflammation including histiocytes, macrophages, neutrophils and plasma cells (Figure 1 Panel F). Identification of Tropheryma whipplei was confirmed using DNA amplification technique (polymerase chain reaction) plus sequencing. This enabled optimisation of post-operative treatment
SC
with oral Co-trimoxazole 960 mg (trimetoprim-sulfametoxazol) after surgery for 12 months. The postoperative course was uneventful at 8-month follow-up with no echocardiographic or clinical evidence
M AN U
of recurrent infection.
DISCUSSION
Whipple’s disease is a rare condition first described by George Hoyt Whipple in 1907, caused by
TE D
Tropheryma whippley. This organism belongs to the Gram-positive actinomycetes and some studies have shown a statistically significantly higher prevalence in farming profession over persons with other occupations. It usually presents with gastrointestinal symptoms whilst affecting the
EP
cardiovascular system to a lesser extent1. The disease is extremely rare with an estimated incidence of below 1/1,000,000. It is strongly prevalent in Caucasian males with a male to female ratio of 8:1, and
AC C
a mean age of onset around 50 years.2 Cardiac involvement has been reported in 17 to 55% of patients with classical Whipple's disease with pericarditis being the most common3. It is very rare that cardiac involvement is the primary and sole presentation in absence of intestinal symptoms. Tropheryma whipplei IE (infective endocarditis) is difficult to diagnose because blood cultures often fail to reveal the organism, resulting in up to 31% of culture-negative cases4. Thus molecular method for the identification of Tropheryma whipplei is an important tool for the management of the uncommon forms of infective endocarditis. Immunohistochemical analysis for T whipplei remains the gold standard for the diagnosis of Whipple disease. It is a sensitive and specific method that can be
ACCEPTED MANUSCRIPT easily performed in most laboratories5. This method offers added specificity over PCR methods owing to the direct visualization of bacilli and antigens within cells in tissue sections and offers increased sensitivity and specificity over the traditional PAS staining method. However the systematic use of PCR amplification of the bacterial 16 rRNA gene, and subsequent sequencing in valvular tissue is
RI PT
increasing the percentage of patients diagnosed with Tropheryma whipplei endocarditis4. The correct diagnosis of Tropheryma whipplei infection is critical because it guides postoperative antimicrobial treatment in the prevention of recurrent endocarditis. The latter occurs commonly without prolonged antibiotic treatment, is then hard to eradicate and reoperations carry substantial morbidity and
SC
mortality.
M AN U
In conclusion, PCR adds substantially to the etiologic diagnosis of IE, leading to institution of appropriate antibiotic therapy. It should be considered in all cases in which routine cultures are negative despite a high index of clinical suspicion of IE.
TE D
Figure Legend Figure 1
EP
Panel A. Detail of the non-coronary aortic cusp appearing thickened (White arrow). Panel B. Mitral valve with the posterior leaflet thickened at the base (white arrow) with further nodular thickening of
AC C
the anterior leaflet (tip of white arrow). Panel C. Intraoperative aspect of the pericardium presenting with multiple calcified nodules scattered across the epicardium. Panel D. Intraoperative aspect of the aortic valve with the non-coronary cusp entirely destroyed adjacent to the abscess (black arrow). Panel E. Intraoperative aspect of the mitral valve presenting with a gross thickening in both mitral leaflets (hash, anterior leaflet; asterisk, posterior leaflet). Panel F. Histological evaluation showing focal myxoid degeneration with fragments of partially hyalinised fibrous connective tissue and extensive amorphous dystrophic calcification accompanied by chronic inflammation including histiocytes, macrophages, neutrophils and plasma cells.
ACCEPTED MANUSCRIPT
REFERENCES 1. Fenollar F, Puéchal X, Raoult D: Whipple's disease. New Eng J Med 2007, 356:55-66.
RI PT
2. Fenollar F, Célard M, Lagier JC, Lepidi H, Fournier PE, Raoult D. Tropheryma whipplei endocarditis.. Emerg Infect Dis 2013;19:1721-30
3. Amendolara M, Barbarino C, Bucca D, Stevanato G, Zucchelli M, Romano F, Baiano L,
SC
Bernardi M, Broggiato A, Ramuscello S, Rizzo M. Whipple's disease infection surgical treatment: presentation of a rare case and literature review. G Chir. 2013 Apr;34:117-21.
M AN U
4. Geissdörfer W, Moos V, Moter A, Loddenkemper C, Jansen A, Tandler R, Morguet AJ, Fenollar F, Raoult D, Bogdan C, Schneider T. High frequency of Tropheryma Whippley in culture negative endocarditis J Clin Microbiol. 2012 Feb;50:216-22. 5. Baisden BL, Lepidi H, Raoult D, Argani P, Yardley JH, Dumler JS. Diagnosis of Wihipple
TE D
disease by immunohistochemical analysis: a sensitive and specific method for the detection of Tropheryma whipplei (the Whipple bacillus) in paraffin-embedded tissue. Am J Clin Pathol.
AC C
EP
2002 Nov;118:742-8.
AC C
EP
TE D
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT
