Effect of immunosuppressive therapy in inflammatory cardiomyopathy: data from The Czech Inflammatory Cardiomyopathy Immunosuppressive Trial.

INTRODUCTION: The indications for specific treatment in the cases of inflammatory cardiomyopathy are based on limited data from several small clinical trials. AIM: A comparison of the effect of two dose regimens of combined immunosuppressive therapy by adding them to conventional heart failure therapy and comparing them with conventional heart failure therapy alone in patients with inflammatory cardiomyopathy. METHODS AND STUDY POPULATION: We enrolled 20 patients; mean age 46.10±7.33 years, duration of symptoms <6 months, LVEF ≤40 %, NYHA class II-IV, with biopsy­proven myocarditis. Patients were randomly separated into groups treated with immunosuppressive therapy in addition to conventional heart failure therapy or to a group treated with conventional heart failure therapy alone. Clinical and echocardiographic parameters were evaluated. RESULTS: The baseline values of LVEF in the group of immunosuppressive therapy (LVEF 22.3±4.7 %) were similar to those in the group treated with conventional heart failure therapy (LVEF 21.7±4.7 %; p=0.757). After twelve months there was no statistically significant difference in LVEF between the two studied groups (LVEF 33.7±9.5 % for the immunosuppressive therapy group and 41.3±13.0 % for the conventional therapy group; p=0.175). CONCLUSION: In our study population, we proved no positive effect of combined immunosuppressive therapy on the left ventricular function over 12 months. The main limitation of the study is the small number of enrolled patients (Tab. 4, Fig. 1, Ref. 35).

[Heart transplantation and the subsequent treatment of AL amyloidosis]. / Transplantace srdce a následná lécba AL-amyloidózy.

UNLABELLED: Severe damage to the heart caused by AL amyloid deposits is a contraindication of high-dose chemotherapy with autologous haematopoietic stem cell transplantation. Severe heart damage caused by AL amyloid results in frequent life-threatening complications, even during the course of the classical chemotherapy treatment and it often makes keeping to the treatment schedule impossible. Scheduling heart transplantation before the treatment of AL amyloidosis will significantly improve the patients overall condition and enable them to undergo the intensive AL amyloidosis treatment with the hope that a long-term complete remission may be achieved. CASE DESCRIPTIONS: Transplantations of heart damaged by AL amyloid deposits were conducted in three patients; two men, age 48 and 54, and one woman, age 63. In the interval of 3-6 months from the heart transplantation before the scheduled AL amyloidosis treatment was initiated, an examination of bone marrow, the concentration of monoclonal immunoglobulin and free light chains was carried out. Both men had more than 10% of plasma cells in the bone marrow after the heart transplantation and the concentrations of the λ free light chains were pathologically increased. During the first-line therapy, autologous haematopoietic stem cells were harvested from peripheral blood after mobilizaton with granulocyte growth factor (filgrastim) at the dose of 5 µg/kg twice a day. During the administration of filgrastim until the end of the haematopoietic stem cell harvest, the combined immunosuppressive treatment was reduced and a corticosteroid dose was compensatory increased. The prophylactic antiviral drug valganciclovir was discontinued during the haematopoietic stem cell harvest. High-dose chemotherapy (melphalan 100 mg/m2) with autologous haematopoietic stem cell transplantation followed. In the interval from administering melphalan until the rise in neutrophil count over 2 x 109/l, antiviral prophylaxis was discontinued again, the immunosuppressive drug doses were reduced and corticoid doses were slightly increased. High-dose chemotherapy with melphalan at the of 100 mg/m2 was tolerated without major complications and without mucositis; however, in neither of the male patients did it lead to a complete haematological remission. Consequently, the second-line therapy followed using bortezomib combined with dexamethasone and also with cyclophosphamide or doxorubicin. One of these two patients reached a complete haematological remission after the bortezomib therapy; the values of free light chains were normal, immunofixation was negative, and clonal plasma cells were absent in the bone marrow. In the case of the other patient, the bortezomib therapy only induced partial remission. In this case, the third-line therapy followed, applying a combination of lenalidomide, dexamethasone and cyclophosphamide. This therapy significantly reduced the values of free light chains; however, their ratio remained pathological. To conclude, the latter response can be described as a very good partial remission. Both men currently show no signs of disease activity and are in a good clinical condition 28 and 30 months after the heart transplantation. The third heart transplantation, due to severe heart damage by AL amyloid deposits, was conducted in a woman aged 63. An examination of this woman three months after the heart transplantation showed that the original pathological values of free light chains became normal. The woman had approx. 8% of clonal plasma cells before the heart transplantation. Three months after the heart transplantation the bone marrow contained only 3% of polyclonal plasma cells. In this case, the immunosuppressive treatment with corticosteroids after the heart transplantation probably induced a complete haematologic remission. The woman is in a complete AL amyloidosis remission seven months after the heart transplantation. CONCLUSION: It was beneficial to perform the heart transplantation first and to initiate the AL amyloidosis treatment no sooner than three months after the heart transplantation in patients with severe heart damage caused by AL amyloid deposits. If the patients are in a good clinical conditions, autologous haematopoietic stem cells can be harvested after the heart transplantation and high-dose chemotherapy can be offered to the patients. If this intensive treatment does not induce remission, it is necessary to apply additional alternative treatments.

Haemolytic anaemia and acute liver failure--the initial manifestations of Wilson's disease.

We describe a case of a 16-year-old girl with Wilson disease, which was initially presented as Coombs-negative haemolytic anaemia and acute liver failure. The diagnosis was based on the findings of low ceruloplasmin serum level and high copper levels both in serum and 24-hour urinary excretion. The patient underwent orthotopic liver transplantation. A DNA-based diagnostic tool confirmed Wilson's disease: the patient was p.H1069Q homozygote. Based on further molecular-genetic examinations in the family, Wilson disease was diagnosed seven days later in one of the patient's asymptomatic brothers. The proband's cousin was confirmed as a carrier of the p.H1069Q mutation (Fig. 1, Ref. 24).

[Giant cell arteritis manifested by bilateral arteritic Anterior Ischaemic Optic Neuropathy (AION)]. / Obrovskobunecná arteriitida manifestující se oboustrannou arteriitickou prední ischemickou neuropatií zrakového nervu (AION).

Giant cell arteritis (GCA) is a systemic vasculitis of unknown etiology affecting medium and large calibre vessels by granulomatous panarteritis with the formation of giant multinucleate cell granulomas. Vision is affected in 25-50% of GCA patients. Affection of vision may be the first GCA symptom or a symptom which occurs weeks or months after the initial symptoms of the disease. Eye symptoms of the disease are mostly a manifestation of occlusion of ocular and orbital blood vessels. Permanent damage to the patient's vision is a serious consequence of visual affection provoked by GCA. Arteritic Anterior Ischaemic Optic Neuropathy (AION) is the most frequent and most serious visual manifestation of GCA. It is manifested by partial or total loss of vision. Arteritic AION therapy in GCA uses high doses ofglucocorticoids, but glucocorticoid therapy has a number of adverse effects. The proofs of the effect of the therapy on the improvement of the vision of patients with visual affection in GCA are not convincing. We report a case of a 76-year old man with biopsy-verified GCA whose primary manifestation was bilateral arteritic AION resulting in a complete loss of vision in one eye and dramatic worsening of visual acuity in the other eye. Glucocorticoid therapy only improved vision in one eye, and had adverse effects. Methotrexate was added to the therapy to achieve a glucocorticoid saving effect. Glucocorticoid therapy could be discontinued after 3 years. In the course of the therapy and for the subsequent 12 months after it was finished, there was no relapse of the underlying disease.

[Heterotopic chondro-osteoplastic metaplasia of the subclavian vein wall after long-term catheterization. Case report]. / Heterotopická chondroosteoplastická metaplazie steny vena subclavia po dlouhodobé kanylaci. Kazuistické sdelení.

A 59-year-old man admitted for i.m. had a 3-way cannula inserted into the right subclavian vein for 31 days. Autopsy revealed a circular firm thickening of the venous wall. Histology identified it as chondroid and osteoid tissue replacing adventitial connective tissue. Unusual chondroosteoplastic metaplasia not described up to now is discussed as about its causes.