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Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Patients with unexplained heart failure, hepatomegaly, nephrotic syndrome, or peripheral neuropathy should be evaluated for primary systemic (amyloid light-chain, or AL) amyloidosis by first seeking evidence of a clonal plasma cell disorder with serum and urine immunofixation studies, as well as a bone marrow biopsy. Immunostaining of the marrow biopsy for lambda and kappa isotypes will usually demonstrate a dominant clonal population of plasma cells if immunofixation studies are negative (less than 10% of cases). Tissue diagnosis of amyloidosis should be sought by biopsy of the abdominal fat or an involved organ. In addition, patients with stable myeloma or monoclonal gammopathy of undetermined significance who develop such conditions or become progressively ill should be evaluated for amyloidosis. We recommend that newly diagnosed patients with AL amyloidosis, who meet criteria for autologous hematopoietic cell transplantation, be considered for high-dose melphalan with stem cell support. Criteria usually include adequate cardiac, pulmonary, and hepatic function. AL amyloidosis patients treated with autologous transplantation frequently achieve durable complete remissions of the plasma cell disease and marked improvement in amyloid-related organ dysfunction. AL amyloidosis patients with dominant cardiac amyloid, who are without symptomatic pleural effusions and have no history of cardiac syncope or symptomatic arrhythmias, may be considered for autologous transplantation but are at increased risk of peritransplant mortality. Autologous transplantation should not routinely be offered to patients with dominant cardiac amyloid with recurrent effusions or histories of syncope or arrhythmias or to patients older than 50 years of age with more than two major organ systems involved (eg, heart, kidneys, liver, and peripheral nerves). We recommend that AL patients with isolated advanced cardiac or hepatic amyloidosis be considered for solid organ replacement followed by autologous transplantation. Otherwise, AL patients who are elderly or ineligible for autologous transplantation may be treated with oral melphalan (Alkeran, GlaxoWellcome, Middlesex, UK) and prednisone; however, because the response rate is only about 25% and the prognosis poor, such patients might also be enrolled on clinical trials of emerging therapies.
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PMID:Primary systemic amyloidosis. 1205 64

Primary amyloidosis is a rare disease, cardiac involvement occurs in up to 40% of patients. Diffuse amyloid deposits cause an impairment of myocardial systolic and diastolic function. In this paper we are presenting a case of a 54-year-old woman. The woman was admitted because of progressive fatigue, dyspnoea, chest pain, later she experienced hypotension, dyspepsia, and enterorrhagia. ECG showed decrease in QRS amplitude. We have found an echocardiographic evidence of wall hypertrophy. Right cardiac catheterization showed a restrictive situation. Immunobinding of serum and urine revealed monoclonal kappa light chains. The diagnosis was determined by rectal biopsy. Unfortunately, amyloid deposits caused progressive heart failure, hemorrhage, and death just before the diagnosis of primary amyloidosis could be determined on the basis of results of the immunofixations of serum and urine proteins (detection of the monoclonal light chains kappa) and from biopsy specimens taken from rectum (amyloid deposits).
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PMID:[Restrictive cardiomyopathy as a manifestation of primary amyloidosis]. 1501 21

Primary amyloidosis is a systemic disorder characterized by the clonal production and tissue deposition of immunoglobulin light chain (LC) proteins. Congestive heart failure remains the greatest cause of death in primary amyloidosis, due to the development of a rapidly progressive amyloid cardiomyopathy. Amyloid cardiomyopathy is largely unresponsive to current heart failure therapies, and is associated with a median survival of less than 6 months and a 5-year survival of less than 10%. The mechanisms underlying this disorder, however, remain unknown. In this report, we demonstrate that physiological levels of human amyloid LC proteins, isolated from patients with amyloid cardiomyopathy (cardiac-LC), specifically alter cellular redox state in isolated cardiomyocytes, marked by an increase in intracellular reactive oxygen species and upregulation of the redox-sensitive protein, heme oxygenase-1. In contrast, vehicle or control LC proteins isolated from patients without cardiac involvement did not alter cardiomyocyte redox status. Oxidant stress imposed by cardiac-LC proteins further resulted in direct impairment of cardiomyocyte contractility and relaxation, associated with alterations in intracellular calcium handling. Cardiomyocyte dysfunction induced by cardiac-LC proteins was independent of neurohormonal stimulants, vascular factors, or extracellular fibril deposition, and was prevented through treatment with a superoxide dismutase/catalase mimetic. This study suggests that cardiac dysfunction in amyloid cardiomyopathy is directly mediated by LC protein-induced cardiomyocyte oxidant stress and alterations in cellular redox status, independent of fibril deposition. Antioxidant therapies or treatment strategies aimed at eliminating circulating LC proteins may therefore be beneficial in the treatment of this fatal disease.
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PMID:Human amyloidogenic light chains directly impair cardiomyocyte function through an increase in cellular oxidant stress. 1504 25

Cardiac involvement by sarcoidosis and concomitant deposition of AL amyloid is an uncommon association. We describe the case of a 53-year-old African-American man with a 7-year history of dilated nonischemic cardiomyopathy and severe cardiac failure who underwent orthotopic heart transplantation. His prior cardiac biopsies had only mild myocyte hypertrophy and minimal interstitial fibrosis. After surgery, numerous sarcoid granulomas and amyloid deposition were identified in the native heart. Six days after the transplant the patient died due to aspiration bronchopneumonia and acute renal failure. At autopsy, both sarcoidosis and immunoglobulin (Ig) lambda light-chain amyloidosis were present in the native atria, lungs, thyroid, liver, spleen, and kidneys. Sarcoid granulomas alone were present in the parathyroids, lymph nodes, and bone marrow. Amyloid deposition alone was present in the aorta, stomach, large bowel, and urinary bladder. There was no evidence of plasma cell dyscrasia, or underlying gammopathy. This unusual association was described in only two other cases in the medical literature. However, this is the first case of sarcoidosis and AL amyloidosis with successful sequencing and identification of Ig lambda light-chain amyloid, and in which there was no evidence of plasma cell dyscrasia.
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PMID:Sarcoidosis and immunoglobulin lambda II light-chain amyloidosis diagnosed after orthotopic heart transplantation: a case report and review of the literature. 1571 64

Recent reports from large amyloidosis referral centers suggest that primary systemic AL amyloidosis patients treated with high-dose melphalan (HDM) and autologous stem cell transplantation (ASCT) survive longer than historical controls treated with less intensive chemotherapy, despite high transplant-related mortality (TRM) rates of >10%. A retrospective review was conducted to determine if the outcome of ASCT for AL amyloidosis at our institution was similar to that reported at major amyloidosis referral centers. Over a 7 year period, we treated a total of 15 AL amyloidosis patients with ASCT, including four with poor prognosis cardiac or multisystem involvement. No TRM was observed. Overall, 10 patients (67%) achieved a complete hematological response and four patients (27%) achieved a complete organ response. The 4-year event-free and overall survival rates were 60% (95% CI 32-89%) and 75% (95% CI 50-100%), respectively. One patient, who presented with cardiac failure and multiorgan involvement with colonic bleeding currently remains in complete remission 62 months post-ASCT. In conclusion, ASCT for primary AL amyloidosis can safely be performed at experienced transplant centers that are not associated with major amyloidosis referral centers, and is feasible for patients who have multisystem involvement, particularly for motivated patients with good performance status.
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PMID:Autologous transplantation for primary systemic AL amyloidosis is feasible outside a major amyloidosis referral centre: the Calgary BMT Program experience. 1606 77

Using the European Group for Blood and Marrow Transplantation (EBMT) registry, we retrospectively studied 19 patients with AL (amyloid light-chain) amyloidosis who underwent allogeneic (allo; n = 15) or syngeneic (syn; n = 4) hematopoietic stem cell transplantation (SCT) between 1991 and 2003. For allo-SCT, full-intensity conditioning was used in 7 patients and reduced-intensity conditioning (RIC) in 8 patients. Engraftment was durable in 12 of those 15 patients. The median follow-up time is 19 months. Kaplan-Meier probabilities of overall and progression-free survival were 60% and 53% at 1 year, respectively. Overall, 40% of patients died of transplant-related mortality (TRM). Best hematologic response after SCT was complete remission (CR) and partial remission (PR) in 8 and 2 patients, respectively, leading to an organ response in 8 of these patients. Seven of the 10 patients in remission are long-term survivors. In 5 of 7 evaluable patients in CR, chronic graft-versus-host disease (GvHD) was observed, indicating the contribution of immune effects to disease control. The main clinical problem was cardiac failure in patients with poor performance status due to amyloidosis or in combination with severe infections. These data suggest that allo-SCT might be a promising and potentially curative treatment modality for selected patients with AL amyloidosis.
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PMID:Allogeneic and syngeneic hematopoietic cell transplantation in patients with amyloid light-chain amyloidosis: a report from the European Group for Blood and Marrow Transplantation. 1629 11

Primary systemic amyloidosis or AL amyloidosis is a rare condition characterized by extracellular deposits of fibrils composed of fragments of immunoglobulin light chains. Widespread deposition of this amyloid in tissues interferes with their normal function and leads to multiple organ failure. Clinical manifestations are highly variable due to the wide range of organs involved. The heart is affected in 90% of cases; in 30% of these, cardiac dysfunction is the form of presentation and in 50% it is the cause of death. The commonest form of cardiovascular manifestation is congestive heart failure due to restrictive cardiomyopathy caused by extensive interstitial infiltration of amyloid into the myocardium. Occasionally, it can present as angina, due to infiltration of amyloid into the walls of small vessels. The authors describe the case of a patient in whom the disease presented simultaneously with heart failure and effort angina, as well as intermittent claudication.
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PMID:Primary amyloidosis as a cause of microvascular angina and intermittent claudication. 1656 9

Involvement of the heart is a common finding in amyloidosis. The heart is usually infiltrated by amyloid fibrils in primary amyloidosis and age-related forms of amyloidosis, less commonly in transthyretin familial amyloidosis, and rarely in secondary amyloidosis. The most common clinical presentation is restrictive cardiomyopathy with right-sided heart failure. The second most frequent presentation is congestive heart failure due to systolic dysfunction, followed by arrhythmias and orthostatic hypotension. The diagnosis of amyloidosis requires tissue sample confirmation; at present, Congo red staining in polarized light is the diagnostic method of choice. The characterization of protein fibril type by immunohistochemistry or biochemistry is essential for patient prognosis and treatment. The therapeutic approach consists of specific treatment of amyloidosis and supportive treatment for cardiac-related symptoms. The treatment depends on the type of amyloidosis and the stage of disease. The mainstay of supportive treatment of cardiac failure is diuretic therapy. Primary amyloidosis treatment protocol includes melphalan and prednisone chemotherapy. Heart transplantation is only a palliative treatment. Stem cell transplantation is an emerging treatment alternative. Combination therapy of melphalan and stem cell transplantation has been shown to be a promising treatment strategy. Secondary amyloidosis requires aggressive treatment of the associated inflammatory and neoplastic process. Age-related (senile) amyloidosis benefits from supportive cardiac treatment when applicable. Transthyretin amyloidosis, the most common cardiac hereditary amyloidosis, is treated by liver or combined liver-heart transplantation. New therapies based on chemical and immunologic reaction with amyloid or its precursor are under intensive development.
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PMID:Current treatment in cardiac amyloidosis. 1707 11

Cardiac amyloidosis can result from any of the systemic amyloidoses. The disease is often characterized by a restrictive cardiomyopathy although the particular signs and symptoms depend in part on the underlying cause. In addition to managing the symptoms of heart failure, treatment options vary depending on the etiology of amyloid deposition. It is therefore critical to identify the cause of cardiac amyloidosis before initiating definitive therapy. We present a patient with presumed immunoglobulin (AL) amyloidosis who had a circulating lambda monoclonal protein, but a bone marrow biopsy with kappa predominant plasma cells. This unusual finding called into question the diagnosis of AL amyloidosis and highlights the importance and difficulty of determining the cause of cardiac amyloid deposition before initiating treatment. We review the different forms of cardiac amyloidosis and propose a diagnostic algorithm to help identify the etiology of cardiac amyloid deposition before beginning therapy.
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PMID:An unusual case of cardiac amyloidosis. 1744 98

Amyloidoses are a heterogeneous group of multisystem disorders, which are characterized by an extracellular deposition of amyloid fibrils. Typically affected are the heart, liver, kidneys, and nervous system. More than half of the patients die due to cardiac involvement. Clinical signs of cardiac amyloidosis are edema of the lower limbs, hepatomegaly, ascites and elevated jugular vein pressure, frequently in combination with dyspnea. There can also be chest pain, probably due to microvessel disease. Dysfunction of the autonomous nervous system or arrhythmias may cause low blood pressure, dizziness, or recurrent syncope. The AL amyloidosis caused by the deposition of immunoglobulin light chains is the most common form. It can be performed by monoclonal gammopathy. The desirable treatment therapy consists of high-dose melphalan therapy twice followed by autologous stem cell transplantation. Due to the high peritransplantation mortality, selection of appropriate patients is mandatory. The ATTR amyloidosis is an autosomal dominant disorder caused by the amyloidogenic form of transthyretin, a plasmaprotein that is synthesized in the liver. Therefore, liver transplantation is the only curative therapy. The symptomatic treatment of cardiac amyloidosis is based on the current guidelines for chronic heart failure according to the patient's New York Heart Association (NYHA) state. Further types of amyloidosis with possible cardiac involvement comprise the senile systemic amyloidosis caused by the wild-type transthyretin, secondary amyloidosis after chronic systemic inflammation, and the beta(2)-microglobulin amyloidosis after long-term dialysis treatment.
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PMID:[Cardiac amyloidosis]. 1834 65


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