A 19-year-old youth was hospitalised because of sudden onset of incomplete lid closure and drooping mouth on the left. He regularly walked through fields and woods; three weeks before admission he had noted swelling and reddening on his neck, which he thought was due to an insect bite. When 9 years old a functional heart murmur and 1 degree AV block (P-R interval 0.25s) had been found. Physical examination showed peripheral facial paresis and a 2/6 systolic murmur over the aortic area.As Borreliosis (Lyme disease) was suspected, relevant laboratory tests were performed. These revealed specific IgM antibodies against Borrelia burgdorferi. Polymerase chain reaction demonstrated B. burgdorferi-specific DNA in cerebrospinal fluid and urine. The ECG showed 1 degree AV block (P-R interval 0.28s).Ceftriaxone was administered at once (4 g, followed by 2 g daily intravenously for 14 days). The P-R interval increased to maximally 0.31 s and transient incomplete right bundle branch block developed on the second day. Long-term ECG monitoring also revealed ventricular arrhythmias (Lown IVb), but they gradually disappeared. The neurological signs regressed completely within five days of the start of treatment, while the P-R interval had returned to its initial value of 0.25 s 3 months later.The case makes clear that an ECG should be recorded in borreliosis even in the absence of cardiac symptoms. Hospitalisation with long-term monitoring becomes necessary if it is abnormal.

The indications for temporary implantation of a vena cava filter remain unclear and there are as yet few data about its complications and reliability. It was the aim of this study to determine the efficacy and complication rate of the temporary use of a vena cava filter (VCF) in a large group of patients at high risk of pulmonary embolism, and thus contribute to defining the indications for such temporary implantation.Between November 1991 and October 1997 a total of 118 VCF were implanted in four groups of a total of 114 patients (67 women, 47 men; average age 45.3 +/- 19.8 [12-82] years) to prevent pulmonary embolism: those (1) with massive or fulminant pulmonary embolism (n = 54); (2) with mechanical thrombus fragmentation and (or) local catheter-delivered systemic thrombolysis in pelvic, leg or caval vein thrombosis (n = 42); (3) with systemic thrombolysis in case of floating thrombi at the femoral, iliac or caval veins (n = 7); and (4) as perioperative measure in caesarean section, venous thrombectomy, other surgical interventions or when anticoagulation had to be discontinued in patients with deep vein thrombosis (n = 11).Filters remained implanted for a mean of 6.1 +/- 3.4 (1-16) days. Placement had to be corrected because of filter dislocation in eight patients. Proven pulmonary embolism occurred after filter implantation in only one patient, after filter displacement into the unthrombosed contralateral iliac vein. Thrombus deposition on the filter before its removal was demonstrated in nine patients: thrombolysis was effective in seven of them, while thrombosed filters had to be removed surgically in two. Residual thrombi were found on the filter in six further patients. No pulmonary embolism occurred in connection with filter removal. Local complications at or around the site of insertion of the introducing catheter occurred in 53 of the 114 patients (46.5%): haematoma in 42, infection in 21 and brachial vein thrombosis in three patients.The rate of clinically relevant pulmonary embolism can probably be reduced to a minimum by the implantation of a temporary vena cava filter. The overall complication rate is high, but serious complications are rare.

BACKGROUND AND OBJECTIVES:The indications for temporary implantation of a vena cava filter remain unclear and there are as yet few data about its complications and reliability. It was the aim of this study to determine the efficacy and complication rate of the temporary use of a vena cava filter (VCF) in a large group of patients at high risk of pulmonary embolism, and thus contribute to defining the indications for such temporary implantation. PATIENTS AND METHODS:Between November 1991 and October 1997 a total of 118 VCF were implanted in four groups of a total of 114 patients (67 women, 47 men; average age 45.3 +/- 19.8 [12-82] years) to prevent pulmonary embolism: those (1) with massive or fulminant pulmonary embolism (n = 54); (2) with mechanical thrombus fragmentation and (or) local catheter-delivered systemic thrombolysis in pelvic, leg or caval vein thrombosis (n = 42); (3) with systemic thrombolysis in case of floating thrombi at the femoral, iliac or caval veins (n = 7); and (4) as perioperative measure in caesarean section, venous thrombectomy, other surgical interventions or when anticoagulation had to be discontinued in patients with deep vein thrombosis (n = 11). RESULTS:Filters remained implanted for a mean of 6.1 +/- 3.4 (1-16) days. Placement had to be corrected because of filter dislocation in eight patients. Proven pulmonary embolism occurred after filter implantation in only one patient, after filter displacement into the unthrombosed contralateral iliac vein. Thrombus deposition on the filter before its removal was demonstrated in nine patients: thrombolysis was effective in seven of them, while thrombosed filters had to be removed surgically in two. Residual thrombi were found on the filter in six further patients. No pulmonary embolism occurred in connection with filter removal. Local complications at or around the site of insertion of the introducing catheter occurred in 53 of the 114 patients (46.5%): haematoma in 42, infection in 21 and brachial vein thrombosis in three patients. CONCLUSIONS:The rate of clinically relevant pulmonary embolism can probably be reduced to a minimum by the implantation of a temporary vena cava filter. The overall complication rate is high, but serious complications are rare.

Background and objectives: The indications for temporary implantation of a vena cava filter remain unclear and there are as yet few data about its complications and reliability. It was the aim of this study to determine the efficacy and complication rate of the temporary use of a vena cava filter (VCF) in a large group of patients at high risk of pulmonary embolism, and thus contribute to defining the indications for such temporary implantation.Patients and methods: Between November 1991 and October 1997 a total of 1 18 VCF were implanted in four groups of a total of 114 patients (67 women, 47 men; average age 45.3 +/- 19.8 [12-82] years) to prevent pulmonary embolism: those (1) with massive or fulminant pulmonary embolism (n=54); (2) with mechanical thrombus fragmentation and (or) local catheter-delivered systemic thromboliysis in pelvic, leg or caval vein thrombosis (n = 42); (3) with systemic thrombolysis in case of floating thrombi at the femoral, iliac or caval veins (n = 7); and (4) as perioperative measure in caesarean section, venous thrombectomy, other surgical interventions or when anticoagulation had to be discontinued in patients with deep vein thrombosis (n = 1 1 ).Results: Filters remained implanted for a mean of 6.1 +/- 3.4 (1 - 16) days. Placement had to be corrected because of filter dislocation in eight patients. Proven pulmonary embolism occured after filter implantation in only one patient, after fitter displacement into the unthrombosed contralateral iliac vein. Thrombus deposition on the filter before its removal was demonstrated in nine patients: thrombolysis was effective in seven of them, while thrombosed filters had to be removed surgically in two. Resicual thrombi were found on the filter in six further patients. No pulmonary embolism occured in connection with filter removal. Local complications at or around the site of insertion of the introducing catheter occurred in 53 of the 114 patients (46.5%): haematoma in 42, infection in 21 and brachial Vein thrombosis in three patients. conclusions: The rate of clinically relevant pulmonary embolism can probably be reduced to a minimum by the implantation of a temporary vena cava filter. The overall complication rate is high, but serious complications are ra re.

Background The outcome of systemic thrombolysis in deep iliac venous thrombosis are unsatisfactory, especially in patients with old thrombosis (older than one week) and extensively occluded veins, The aim of this study was to achieve a higher patency rate in deep venous thrombosis by a preceding mechanical fragmentation of thrombus mass and a subsequent catheter directed thrombolysis. Patients and methods: 12 patients (3 males, 9 females; mean age 36.1 years) suffering from thrombosis of pelvic veins were treated by means of the percutaneous transluminal thrombus fragmentation and catheter directed thrombolysis. In addition, in two patients a total and in one patient a partial occlusion of the inferior vena cava was found. The median of duration of symptoms before fragmentation by a balloon catheter (8-12 mm) was 6.5 days (1-28 days). In seven patients preceding systemic thrombolytic therapy had failed. A temporary vena cava filter was placed below the renal veins before fragmentation to prevent pulmonary embolism. Results: The thrombotic area was passed by guide-wire in all cases. After thrombolysis with urokinase (50-150,000 U/h) for a mean of 4,3 days an anterograde flow (TIMI II-III) was reestablished in 10 out of 12 patients. In two out of three patients with vena cava involvement, venous flow was successfully reestablished; in the third patient an early reocclusion occurred because of a heparin associated thrombocytopenia syndrome. In 5/12 patients blood transfusions were necessary. In two patients bleeding complication was directly related to the interventional procedure. Conclusions Percutaneous transluminal thrombus fragmentation and subsequent thrombolysis represent an efficient procedure after unsuccessful systemic lysis in venous iliac thrombosis and a primary therapeutical option in vena cava thrombosis.

Objective: To investigate plasma tumor necrosis factor (TNF)alpha, tumor necrosis factor alpha Soluble receptor I, interleukin-1 beta and neopterin concentrations as markers of monocyte activation in patients with heart failure. Study design: The group consisted of patients with heart failure due to dilated cardiomyopathy (n=19) and coronary artery disease (n=11). Patients without cardiac failure served as controls (n=10). Results: TNF alpha concentrations were elevated only in heart failure patients with coronary artery disease (2.9+/-0.3 pg/ml versus 1.7+/-0.3 pg/ml; P<0.05). When the patients were grouped according to acute and chronic failure, TNF alpha concentrations were significantly elevated in acute failure (3.1+/-0.4 pg/ml, n=6 versus 1.7+/-0.2 pg/ml, n=8; P<0.05). TNF alpha concentrations were elevated in patients with coronary artery disease and chronic heart failure compared to coronary artery disease patients without failure (2.0+/-0.4 pg/ml, n=6 versus 1.8+/-0.3 pg/ml, n=7; P<0.05). A higher proportion of patients with myocardial insufficiency showed increased lipopolysaccharide-inducible TNF alpha concentrations (10/30 versus 0/9, P<0.05). Conclusions: TNF alpha is elevated in patients with acute cardiac decompensation. Among patients with chronic heart failure only those with coronary artery disease exhibit increased levels. Cytokine concentrations are similar in heart failure due to dilated cardiomyopathy and coronary artery disease. Monocytes of patients suffering from cardiac insufficiency show an increased sensitivity towards stimuli such as lipopolysaccharides. (C) 1998 Elsevier Science Ireland Ltd.

Enteroviruses are known as major infectious agents for inflammatory heart diseases such as myocarditis and dilated cardiomyopathy (DCM). Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVC) is characterized by replacement of right ventricular myocardium by fatty and fibrous tissue. In about 65% of patients inflammatory infiltrates suggest an inflammatory or infectious etiopathogenesis. To test this hypothesis, we investigated endomyocardial biopsies of patients with ARVC, with myocarditis or DCM, and from patients with non-inflammatory cardiac disorders for the presence of enteroviral genome. Enteroviral RNA with homology to coxsackieviruses type B was detected in 3 of 8 patients with ARVC (37.5%), in 7 of 23 patients with myocarditis or DCM (30.4%), but in none of 5 patient with non-infectious myocardial diseases (p < 0.05 compared to ARVC patients). These results support earlier suggestions that coxsackievirus infection of the myocardium is possibly related to the pathogenesis of ARVC.

As enterovirus infections of the heart cause myocarditis and eventually congestive heart failure, the antiviral activity of ribavirin was studied in coxsackie virus B3 (CVB3)-infected carrier cultures of human myocardial fibroblasts. Cultures were infected 7 days before application of ribavirin and effects were evaluated over a period of 16 days by plaque assays and in situ hybridization. Compared to the low antiviral activity in HeLa cells, ribavirin was highly active in reducing infectious virus yields in human myocardial fibroblasts, for example, to 2.0 x 10(3) pfu/ml with 25 microg/ml and to 1.3 x 10(2) pfu/ml with 50 microg/ml (4.3 x 10(4) pfu/ml in infected controls). Moreover, 100 microg ribavirin/ml completely suppressed infectious virus progeny in two of three cultures, and reduced the number of infected cells from 14.3 to 0.3% as determined by in situ hybridization, whereas up to 3200 microg ribavirin/ml did not result in a significant cytotoxic effect. Interaction with interferon-alpha (IFN-alpha) was additive to slightly synergistic in reducing the number of infected cells and virus yields. In conclusion, our results suggest a cell-specific high activity of ribavirin in human myocardial fibroblasts and indicate the importance of using organ-specific cells for testing antiviral agents in myocarditis. Furthermore, the usefulness of in situ hybridization for determining the long term effects of antivirals in carrier state cell cultures was demonstrated.

We compared the antiviral activities of three recombinant human interferons (IFN-alph2a, IFN-beta, and IFN-gamma) in cultured human myocardial fibroblasts to select a candidate for trial in heart disease induced by cardiotropic enterovirus, e.g., coxsackievirus B3 (CVB3). Cells were exposed to CVB3, and after 7 days, when a persistent infection had developed, IFN was added. Virus yields were measured on alternate days for the next 7 or 16 days, and IFN activity was assessed as the percentage reduction in yield. IFN-gamma and IFN-beta were both highly active and reduced virus yields by 2 log (EC(99)) at concentrations of 23.4 IU/ml (SD = 8.6) and 10.1 IU/ml (SD = 3.2), respectively; with 250 IU/ml of either IFN, no infectious virus was formed. Unexpectedly, IFN-alpha2a (EC(99)> 1250 IU/ml) was at least 120 times less active than IFN-beta; after use for 8 days or more, the minor effects it produced were no longer related to the concentration applied. Despite the pharmacokinetic advantages of IFN-alpha2a, our data suggest that IFN-beta should in preference be evaluated in the clinic.

History and clinical findings: A 19-year-old youth was hospitalised because of sudden onset of incomplete lid closure and drooping mouth on the left. He regularly walked through fields and woods; three weeks before admission he had noted swelling and reddening on his neck, which he thought was due to an insect bite. When 9 years old a functional heart murmur and 1 degrees AV block (P-R interval 0,25 s) had been found, Physical examination showed peripheral facial paresis and a 2/6 systolic murmur over the aortic area.Investigations: As Borreliosis (Lyme disease) was suspected, relevant laboratory tests were performed. These revealed specific IgM antibodies against Borrelia burgdorferi. Polymerase chain reaction demonstrated B. burgdorferi-specific DNA in cerebrospinal fluid and urine. The ECC showed 1 degrees AV block (P-R interval 0.28 s).Treatment and course: Ceftriaxone was administered at once (4 g, followed by 2 g daily intravenously for 14 days). The P-R interval increased to maximally 0.31 s and transient incomplete right bundle branch block developed on the second day. Long-term ECG monitoring also revealed ventricular arrhythmias (Lown IVb), but they gradually disappeared. The neurological signs regressed completely within five days of the start of treatment, while the P-R interval had returned to its initial value of 0.25 s 3 months later.Conclusion: The case makes clear that an ECG should be recorded in borreliosis even in the absence of cardiac symptoms. Hospitalisation with long-term monitoring becomes necessary if it is abnormal.

HISTORY AND CLINICAL FINDINGS:A 19-year-old youth was hospitalised because of sudden onset of incomplete lid closure and drooping mouth on the left. He regularly walked through fields and woods; three weeks before admission he had noted swelling and reddening on his neck, which he thought was due to an insect bite. When 9 years old a functional heart murmur and 1 degree AV block (P-R interval 0.25s) had been found. Physical examination showed peripheral facial paresis and a 2/6 systolic murmur over the aortic area. INVESTIGATIONS:As Borreliosis (Lyme disease) was suspected, relevant laboratory tests were performed. These revealed specific IgM antibodies against Borrelia burgdorferi. Polymerase chain reaction demonstrated B. burgdorferi-specific DNA in cerebrospinal fluid and urine. The ECG showed 1 degree AV block (P-R interval 0.28s). TREATMENT AND COURSE:Ceftriaxone was administered at once (4 g, followed by 2 g daily intravenously for 14 days). The P-R interval increased to maximally 0.31 s and transient incomplete right bundle branch block developed on the second day. Long-term ECG monitoring also revealed ventricular arrhythmias (Lown IVb), but they gradually disappeared. The neurological signs regressed completely within five days of the start of treatment, while the P-R interval had returned to its initial value of 0.25 s 3 months later. CONCLUSION:The case makes clear that an ECG should be recorded in borreliosis even in the absence of cardiac symptoms. Hospitalisation with long-term monitoring becomes necessary if it is abnormal.

OBJECTIVES:Endomyocardial biopsy samples from patients with idiopathic dilated cardiomyopathy were screened for the presence of enterovirus genome. Patients with enterovirus-positive samples were further studied with regard to disease course, histologic variables and response to interferon-alpha treatment. BACKGROUND:Studies of patients with idiopathic dilated cardiomyopathy have reported widely divergent clinical outcomes, suggesting that there is no unique underlying pathogenetic mechanism. METHODS:Five left ventricular endomyocardial biopsy samples were screened for the presence of the enterovirus genome by an established in situ hybridization technique in combination with a histologic, histomorphometric and immunohistologic workup. The course of the disease was then prospectively followed for up to 50 months. Virus-positive patients whose condition deteriorated were treated with interferon-alpha. RESULTS:Of 77 patients, 20 (26%) had enterovirus-positive and 57 (74%) enterovirus-negative biopsy samples. During a mean follow-up period of 25.8 +/- 13.7 months, 1 patient in the enterovirus-positive group and 11 in the enterovirus-negative group died. Four patients in the enterovirus-negative group underwent heart transplantation (p < 0.05). The surviving 19 enterovirus-positive patients had a decrease in mean left ventricular end-diastolic diameter from 66 to 61 mm (p < 0.05) and a mean increase in left ventricular ejection fraction from 0.35 to 0.43 (p < 0.05). In contrast, enterovirus-negative patients had no significant change in end-diastolic diameter or left ventricular ejection fraction. Four patients in the enterovirus-positive group whose condition deteriorated were treated with a 6-month course of subcutaneous interferon-alpha (3 x 10(6) U every second day). This treatment induced hemodynamic improvement in all four patients and eliminated the persistent enteroviral infection in two. CONCLUSIONS:Enterovirus-positive patients have a better heart transplantation-free survival rate and hemodynamic course, with fewer histologic changes, than do enterovirus-negative patients. In addition, enterovirus-positive patients respond favorably to interferon-alpha treatment. These observations indicate that myocardial enteroviral infection with associated left ventricular dysfunction is a distinct disease entity with a benign course.

Cultured human myocardial fibroblasts of pediatric origin seem to be a useful species-specific model for studying various heart diseases which involve the myocardial interstitium, for example enterovirus heart disease. Cells were propagated from small samples of human ventricular tissues (0.2 g) obtained from standard surgical procedure for the correction of Fallot-tetralogy. Cultured cells exhibited typical fibroblastoid morphology over a period of 4 months and were uniformly immunoreactive with a monoclonal antibody directed against prolyl-4-hydroxylase, a marker enzyme of fibroblasts. Infection of cell cultures with coxsackievirus B3, a cardiotropic enterovirus, resulted in a typical carrier-state type of virus persistence. Average virus titers of 2.3 x 10(5) plaque-forming units/ml (SD = 9.9 x 10(4)) were maintained over a period of up to 10 weeks by productive infection of about 8-10% of the cell population, Coxsackievirus B3 carrier cultures of human myocardial fibroblasts were used to evaluate in vitro the long-term antiviral effects of recombinant interferon alpha-2a and natural human interferon-alpha. Recombinant interferon-alpha reduced virus yields by 90% with a concentration of 423 IU/ml. whereas with natural interferon-alpha a 90% reduction of virus yields was achieved with concentrations as low as 21 IU/ml. Antiviral effects of both recombinant and natural interferon-alpha were highly specific and not related to inhibition of cell-proliferation (<50% with interferon-alpha concentrations as high as 6250 IU/ml). Since effective concentrations of interferon-alpha can be easily attained in vivo with subcutaneous application, interferon-alpha (in particular: natural interferon-alpha) may become useful in the treatment of patients with enterovirus myocarditis and enterovirus induced dilated cardiomyopathy. (C) 1995 Academic Press Limited

Indium-111-antimyosin Fab imaging has been used to indicate myocardial injury. This report describes antimyosin accumulation in two patients with myocardial involvement in systemic lupus erythematosus. Both patients complained of chest pain, and significant stenoses of extramural coronary arteries were ruled out by angiography. The first patient, a 64-yr-old woman, had immunopathologic findings suggestive of systemic lupus. Indium-111-antimyosin Fab imaging showed myocardial tracer uptake. This prompted endomyocardial biopsy providing evidence of systemic lupus. The patient improved under immunosuppressive therapy. The second patient, a 47-yr-old man, had systemic lupus diagnosed by immunopathologic findings and skin biopsy. He had evidence of pericarditis on electrocardiography and echocardiography. Indium-111-antimyosin Fab imaging demonstrated additional myocardial involvement, which supported the initiation of immunosuppressive therapy. Our results suggest that 111In-antimyosin Fab imaging may provide valuable diagnostic information and influence patient management in systemic lupus erythematosus with suspected myocardial involvement.

Seventy-seven consecutive patients with dilated cardiomyopathy underwent left ventricular endomyocardial biopsy. In 20 biopsies (26%) enteroviral RNA was detected by in-situ hybridization. After an average observation period of more than 2 years only one patient had died in the enterovirus positive (ev+) group compared with 11 deaths and four heart transplantations in the enterovirus negative (ev-) group. After a mean follow-up of 16 +/- 9 months haemodynamic evaluation of the surviving ev+ patients showed significantly better results with respect to left ventricular ejection fraction and left ventricular end-diastolic diameter. The four ev+ patients with haemodynamic deterioration were given interferon-alpha, 3 million units subcutaneously every other day for six months. No severe side effects were seen and all four patients improved according to their haemodynamic and clinical parameters. In two of the four patients enteroviral RNA was not detectable in a subsequent biopsy.

In 1985, myocarditis was diagnosed by endomyocardial biopsy in a 53-year-old woman who was free of symptoms of heart insufficiency. Immunosuppressive therapy with azathioprine and prednisolone was prescribed as the patient had deteriorated to NYHA II heart insufficiency in March 1986. When application of immunosuppressive agents was terminated in 1987, serial endomyocardial biopsies revealed no signs of myocarditis, thus indicating effectiveness of immunosuppression. Nevertheless, the patient had worsened clinically and hemodynamically. At follow-up in 1991, the patient had progressed to dilated cardiomyopathy resulting in NYHA III heart insufficiency. Enterovirus infection of the heart was detected by in situ nucleic acid hybridization. In addition, retrospective serology indicated a significant increase of coxsackievirus B2 antibodies between 1985 and 1991. Investigational antiviral therapy with recombinant interferon alpha-2a was tolerated well and a favorable clinical, hemodynamic, and virologic response was observed. Thus, progression of biopsy-proven myocarditis to dilated cardiomyopathy may have been facilitated by immunosuppressive therapy in enterovirus infection. Antiviral therapy might be advantageous in patients with enterovirus myocarditis and dilated cardiomyopathy.

Enteroviruses are thought to play a pathogenetic role in the development of human idiopathic dilated cardiomyopathy (IDC). Reports of the percentage of patients with IDC or myocarditis and detection of enteroviral RNA in the myocardium range from 17% to 30% [6, 8].