Original article Herz DOI 10.1007/s00059-015-4308-1 Received: 14 February 2015 Accepted: 8 March 2015 © Urban & Vogel 2015
Petr Kuchynka1,2 · Tomas Palecek1,2 · Stepan Havranek1 · Ivana Vitkova3 · Eduard Nemecek1 · Radka Trckova1 · Dagmar Berenová4 · Daniel Krsek4 · Jana Podzimkova1 · Michal Fikrle1 · Barbara Anna Danek1 · Ales Linhart1 1 2nd Department of Medicine—Department of Cardiovascular Medicine, First Faculty of Medicine,
Charles University in Prague and General University Hospital in Prague, Prague 2, Czech Republic 2 International Clinical Research Center, St. Anne’s University Hospital in Brno, Brno, Czech Republic 3 Institute of Pathology, First Faculty of Medicine, Charles University in Prague and
General University Hospital in Prague, Prague, Czech Republic 4 The National Institute of Public Health, Prague, Czech Republic
Recent-onset dilated cardiomyopathy associated with Borrelia burgdorferi infection Dilated cardiomyopathy (DCM) is defined by the presence of left ventricular (LV) dilatation and LV systolic dysfunction in the absence of any abnormal loading conditions or coronary artery disease sufficient to cause global systolic impairment [1]. It represents the third most common cause of heart failure with reduced ejection fraction, and the most frequent reason for heart transplantation [2]. Although a genetic basis has been found in up to 25 % of patients, the majority of cases are sporadic, with no identified genetic etiology. Infectious or immune-mediated pathogenesis is suspected in many patients suffering from DCM. Although viral infection is considered to be the most common cause of DCM resulting from previous myocarditis, nonviral agents are also involved in DCM pathogenesis. Lyme disease caused by spirochaetes of the Borrelia burgdorferi (Bb) sensu lato species has been shown to result in myocarditis and inflammatory dilated cardiomyopathy. Borrelia afzelii and garinii infections account for most Lyme borreliosis cases in Europe, whereas Borrelia garinii is predominant in Asia, and Borrelia burgdorferi sensu stricto in North America [3]. Lyme disease is the most common tick-borne disease in the northern hemisphere [4]. Borrelia burgdorferi infection initially affects the skin, but if left untreated, it may spread to the nervous system, joints, and heart. According to published
2
Herz
data, the prevalence of cardiac involvement ranges from 0.5 to 10 % [5]. Conduction and rhythm disturbances have been noted most frequently; however, other cardiac manifestations including endocarditis, myocarditis, and pericarditis have also been reported [5]. The epidemiology and natural history of cardiac involvement are not well documented. Borrelia burgdorferi was first cultured from the myocardium of a 54-year-old man with longstanding DCM in 1990 [6]. However, other authors investigating myocardial samples obtained from patients with end-stage DCM using polymerase chain reaction (PCR) were unable to detect Bb in any of the subjects [7, 8]. Moreover, in endomyocardial samples from patients with suspected inflammatory heart disease (including individuals with DCM) and positive serology for Bb, the Bb genome was not revealed by PCR in any subject [9]. In a recently published pilot study, we reported a prevalence of 21 % of confirmed Bb in endomyocardial biopsy (EMB) specimens obtained from 39 patients with recent-onset DCM [10]. Similar findings were subsequently published by other authors, suggesting that Central Europe represents an endemic area with a relatively high frequency of Bbrelated DCM [11]. In the current study we aimed to assess the outcomes of targeted antibiotic treatment in individuals with recent-onset DCM and EMB positive for the presence of Bb genome.
Patients and methods Between January 2007 and May 2012 we investigated 110 consecutive patients (53 ± 11 years, 34 women) who were referred to our institution for further evaluation with the diagnosis of recent-onset unexplained DCM. All of these patients had a history of DCM/heart failure symptoms for less than 12 months, and LV systolic dysfunction defined as LV ejection fraction 70 kg), in addition to conventional heart failure therapy [15]. Signed informed consent was obtained from all patients in a format standardized by our institution. This investigation conformed to the principles outlined in the Declaration of Helsinki. Data are expressed as mean ± standard deviation (SD) or as number and percentage of subjects. Differences were compared using the paired and unpaired Student’s t test. A p value of 0.04 μg/l) in 38 % of the Bbpositive patients. Histological signs of active or borderline myocarditis according to the Dallas criteria were not found in any EMB sample. Immunohistochemical analysis revealed signs of myocardial inflammation in eight (36 %) Bb-positive patients. Electron microscopy revealed evidence of Bb (. Fig. 2) in nine (41 %) individuals. The concomitant presence of a viral genome was detected by PCR in ten (45 %) cases. Serological analysis demonstrated IgG antibodies against Bb in eight (36 %) Bbpositive patients; however, IgM antibodies were not detected in any subject.
P. Kuchynka · T. Palecek · S. Havranek · I. Vitkova · E. Nemecek · R. Trckova · D. Berenová · D. Krsek · J. Podzimkova · M. Fikrle · B.A. Danek · A. Linhart
Clinical and echocardiographic treatment outcomes in Bb-positive patients The echocardiographic data and NYHA classification of Bb-positive patients at baseline and 12 months after ceftriaxone therapy are shown in . Table 3. There was a significant increase in LV ejection fraction and a decrease in LV end-diastolic and end-systolic diameters after therapy. More specifically, LV ejection fraction completely normalized (LV ejection fraction ≥ 55 %) in five (23 %) Bb-positive patients and improved (∆ LV ejection frac-
4
Herz
Recent-onset dilated cardiomyopathy associated with Borrelia burgdorferi infection Abstract Background. Several recent small studies have suggested a causal link between Lyme disease and dilated cardiomyopathy (DCM) by demonstrating the presence of the Borrelia burgdorferi (Bb) genome in the myocardium of patients with recent-onset DCM. The aim of this study was to further investigate the effect of targeted antibiotic treatment of Bb-related recent-onset DCM in a larger cohort of patients. Patients and methods. We performed endomyocardial biopsy (EMB) in 110 individuals (53 ± 11 years, 34 women) with recent-onset unexplained DCM, and detected the Bb genome in 22 (20 %) subjects. Bb-positive patients were subsequently treated with intravenous ceftriaxone for 21 days in addition to conventional heart failure medication. Results. At the 1-year follow-up, a significant improvement in left ventricular (LV) ejec-
tion fraction (26 ± 6 vs. 44 ± 12 %; p
Petr Kuchynka1,2 · Tomas Palecek1,2 · Stepan Havranek1 · Ivana Vitkova3 · Eduard Nemecek1 · Radka Trckova1 · Dagmar Berenová4 · Daniel Krsek4 · Jana Podzimkova1 · Michal Fikrle1 · Barbara Anna Danek1 · Ales Linhart1 1 2nd Department of Medicine—Department of Cardiovascular Medicine, First Faculty of Medicine,
Charles University in Prague and General University Hospital in Prague, Prague 2, Czech Republic 2 International Clinical Research Center, St. Anne’s University Hospital in Brno, Brno, Czech Republic 3 Institute of Pathology, First Faculty of Medicine, Charles University in Prague and
General University Hospital in Prague, Prague, Czech Republic 4 The National Institute of Public Health, Prague, Czech Republic
Recent-onset dilated cardiomyopathy associated with Borrelia burgdorferi infection Dilated cardiomyopathy (DCM) is defined by the presence of left ventricular (LV) dilatation and LV systolic dysfunction in the absence of any abnormal loading conditions or coronary artery disease sufficient to cause global systolic impairment [1]. It represents the third most common cause of heart failure with reduced ejection fraction, and the most frequent reason for heart transplantation [2]. Although a genetic basis has been found in up to 25 % of patients, the majority of cases are sporadic, with no identified genetic etiology. Infectious or immune-mediated pathogenesis is suspected in many patients suffering from DCM. Although viral infection is considered to be the most common cause of DCM resulting from previous myocarditis, nonviral agents are also involved in DCM pathogenesis. Lyme disease caused by spirochaetes of the Borrelia burgdorferi (Bb) sensu lato species has been shown to result in myocarditis and inflammatory dilated cardiomyopathy. Borrelia afzelii and garinii infections account for most Lyme borreliosis cases in Europe, whereas Borrelia garinii is predominant in Asia, and Borrelia burgdorferi sensu stricto in North America [3]. Lyme disease is the most common tick-borne disease in the northern hemisphere [4]. Borrelia burgdorferi infection initially affects the skin, but if left untreated, it may spread to the nervous system, joints, and heart. According to published
2
Herz
data, the prevalence of cardiac involvement ranges from 0.5 to 10 % [5]. Conduction and rhythm disturbances have been noted most frequently; however, other cardiac manifestations including endocarditis, myocarditis, and pericarditis have also been reported [5]. The epidemiology and natural history of cardiac involvement are not well documented. Borrelia burgdorferi was first cultured from the myocardium of a 54-year-old man with longstanding DCM in 1990 [6]. However, other authors investigating myocardial samples obtained from patients with end-stage DCM using polymerase chain reaction (PCR) were unable to detect Bb in any of the subjects [7, 8]. Moreover, in endomyocardial samples from patients with suspected inflammatory heart disease (including individuals with DCM) and positive serology for Bb, the Bb genome was not revealed by PCR in any subject [9]. In a recently published pilot study, we reported a prevalence of 21 % of confirmed Bb in endomyocardial biopsy (EMB) specimens obtained from 39 patients with recent-onset DCM [10]. Similar findings were subsequently published by other authors, suggesting that Central Europe represents an endemic area with a relatively high frequency of Bbrelated DCM [11]. In the current study we aimed to assess the outcomes of targeted antibiotic treatment in individuals with recent-onset DCM and EMB positive for the presence of Bb genome.
Patients and methods Between January 2007 and May 2012 we investigated 110 consecutive patients (53 ± 11 years, 34 women) who were referred to our institution for further evaluation with the diagnosis of recent-onset unexplained DCM. All of these patients had a history of DCM/heart failure symptoms for less than 12 months, and LV systolic dysfunction defined as LV ejection fraction 70 kg), in addition to conventional heart failure therapy [15]. Signed informed consent was obtained from all patients in a format standardized by our institution. This investigation conformed to the principles outlined in the Declaration of Helsinki. Data are expressed as mean ± standard deviation (SD) or as number and percentage of subjects. Differences were compared using the paired and unpaired Student’s t test. A p value of 0.04 μg/l) in 38 % of the Bbpositive patients. Histological signs of active or borderline myocarditis according to the Dallas criteria were not found in any EMB sample. Immunohistochemical analysis revealed signs of myocardial inflammation in eight (36 %) Bb-positive patients. Electron microscopy revealed evidence of Bb (. Fig. 2) in nine (41 %) individuals. The concomitant presence of a viral genome was detected by PCR in ten (45 %) cases. Serological analysis demonstrated IgG antibodies against Bb in eight (36 %) Bbpositive patients; however, IgM antibodies were not detected in any subject.
P. Kuchynka · T. Palecek · S. Havranek · I. Vitkova · E. Nemecek · R. Trckova · D. Berenová · D. Krsek · J. Podzimkova · M. Fikrle · B.A. Danek · A. Linhart
Clinical and echocardiographic treatment outcomes in Bb-positive patients The echocardiographic data and NYHA classification of Bb-positive patients at baseline and 12 months after ceftriaxone therapy are shown in . Table 3. There was a significant increase in LV ejection fraction and a decrease in LV end-diastolic and end-systolic diameters after therapy. More specifically, LV ejection fraction completely normalized (LV ejection fraction ≥ 55 %) in five (23 %) Bb-positive patients and improved (∆ LV ejection frac-
4
Herz
Recent-onset dilated cardiomyopathy associated with Borrelia burgdorferi infection Abstract Background. Several recent small studies have suggested a causal link between Lyme disease and dilated cardiomyopathy (DCM) by demonstrating the presence of the Borrelia burgdorferi (Bb) genome in the myocardium of patients with recent-onset DCM. The aim of this study was to further investigate the effect of targeted antibiotic treatment of Bb-related recent-onset DCM in a larger cohort of patients. Patients and methods. We performed endomyocardial biopsy (EMB) in 110 individuals (53 ± 11 years, 34 women) with recent-onset unexplained DCM, and detected the Bb genome in 22 (20 %) subjects. Bb-positive patients were subsequently treated with intravenous ceftriaxone for 21 days in addition to conventional heart failure medication. Results. At the 1-year follow-up, a significant improvement in left ventricular (LV) ejec-
tion fraction (26 ± 6 vs. 44 ± 12 %; p
