Senile systemic amyloidosis presenting with heart failure: a comparison with light chain-associated amyloidosis

BACKGROUND: Small deposits of amyloid are often found in the hearts of elderly patients. However, extensive deposition of transthyretin-derived amyloid fibrils in the heart (senile systemic amyloidosis [SSA]) can cause heart failure. The clinical features of SSA that involve the heart are ill defined, and the condition may be overlooked as a cause of heart failure. We sought to better define the clinical, echocardiographic, and electrocardiographic features of cardiac involvement in SSA and to compare them with the findings in patients with light chain-associated (AL) amyloidosis that affects the heart. METHODS: Eighteen consecutive patients with SSA and heart failure evaluated at a tertiary referral center for the diagnosis and treatment of amyloidosis were compared with 18 randomly selected patients with AL amyloidosis that involved the heart. All patients underwent a complete clinical and biochemical evaluation. Echocardiograms and electrocardiograms were interpreted by blinded investigators. RESULTS: Patients with SSA were older than those with AL amyloidosis and were all male. Proteinuria (protein output of >1 g per 24 hours) was common in AL amyloidosis but was not present in SSA. Left ventricular wall thickness was greater in patients with SSA than those with AL amyloidosis, but despite thicker walls and older age, the severity of heart failure was less in the SSA group and the median survival was much longer (75 vs 11 months; P = .003). CONCLUSIONS: Senile systemic amyloidosis is a disorder of elderly men and is characterized by amyloidosis clinically limited to the heart. In contrast to the rapid progression of heart failure in AL amyloidosis, SSA results in slowly progressive heart failure. The difference in survival, despite evidence of more myocardial disease in the senile group, suggests that heart failure in AL amyloidosis may have a toxic component, possibly related to the circulating monoclonal light chain.     

Primary systemic amyloidosis presenting as constrictive pericarditis

The most frequent presentation of cardiac amyloidosis is with endomyocardial deposition, and resultant restrictive cardiomyopathy. We present a case of primary systemic amyloidosis causing constrictive pericarditis (CP) and congestive heart failure without clinical evidence of endomyocardial deposition. A comprehensive evaluation by noninvasive and invasive studies facilitated the differentiation of CP from restrictive cardiomyopathy and the patient was effectively treated with pericardectomy. To our knowledge, this is the first documented case of primary systemic amyloidosis causing selective CP with successful antemortem diagnosis and treatment in a young man.     

Primary systemic amyloidosis with nephrosis

A fatal case of primary systemic amyloidosis is reported. The patient was a sixty-six year old woman who presented the clinical and laboratory signs of nephrosis. Widespread amyloid infiltration was demonstrated at autopsy and renal amyloidosis accounted for the nephrotic syndrome.     

Primary systemic amyloidosis

Two cases of primary systemic amyloidosis are presented. These bring the total number now in the literature to forty-eight. The disease affects middle aged or elderly individuals, begins insidiously and is slowly progressive. It is characterized chiefly by congestive heart failure, macroglossia, asthenia and weight loss. The Congo red test is often negative and biopsy is the best means for establishing the diagnosis.The amyloid deposits have atypical staining properties and exhibit a striking affinity for muscle tissue: smooth, striated and cardiac. The heart, tongue, gastrointestinal tract musculature, skeletal muscles and the media of small arteries everywhere are most conspicuously affected.Amyloid in multiple myeloma and primary amyloid are much alike in organ distribution, age incidence and tinctorial irregularity.     

Primary macroglobulinemia with hypercalcemia, renal failure and systemic amyloidosis]

This report deals with an unusual case of primary macroglobulinemia with hypercalcemia, chronic renal failure and systemic amyloidosis. In May 1990, a 63-year-old male was transferred to our hospital because of hypercalcemia (13.5 mg/dl) and renal failure. Clinical examinations showed anemia, macroglossia, lymph node swellings and hepatomegaly. Laboratory findings included Bence-Jones (kappa type) proteinuria (0.8 g/day), a monoclonal gammopathy of the IgM-kappa type (2.8 g/dl), a proliferation of lymphoid cells in the peripheral blood (5%) and the bone marrow (59.6%), and lymphomatous involvement of an inguinal lymph node. Serum creatinine concentration was 8.5 mg/dl. The serum levels of parathormone and vitamin D3 metabolites were normal. The roentgenogram of bones showed a compression fracture of the lumbar spine and systemic osteoporosis. The treatment included eel calcitonin, prednisolone and the CHOP regimen, followed by hemodialysis and plasmapheresis. The serum level of IgM increased to 4.6 g/dl. The patient died three months later and postmortem examination demonstrated marked systemic amyloidosis.     

Primary systemic amyloidosis presenting as polymyalgia rheumatica and giant cell arteritis

Primary systemic amyloidosis or AL-amyloidosis is an uncommon disease characterized by the accumulation in vital organs of a fibrillar protein consisting of monoclonal light chains. It is a plasma-cell dyscrasia related to multiple myeloma where clonal plasma cells in the bone marrow produce immunoglobulins that are amyloidogenic. A monoclonal component is present in the serum or urine of 90% of patients. The presentation of most patients with AL amyloidosis is usually related to congestive heart failure, nephrotic syndrome o peripheral neuropathy, but there are unusual features suggesting giant cell arteritis (GCA) and polymyalgia rheumatic (PMR). Although in the majority of AL cases the plasma cells clone is small, the assumption is that the outcome of the disease is uniformly fatal (median survival 12-15 months) and treatment is analogous to those used in malignant proliferative disease. We describe a patient with AL amyloidosis who presented with manifestations of GCA and PMR, and we review the main characteristics of primary amyloidosis.     

Primary systemic amyloidosis presenting as giant cell arteritis and polymyalgia rheumatica

Primary systemic amyloidosis may present with features suggesting a vasculitis, including giant cell arteritis (GCA) and polymyalgia rheumatica (PMR). In this report, we describe the clinical characteristics, temporal artery biopsy findings, and the response of vascular and musculoskeletal symptoms to corticosteroid therapy in 4 patients with primary systemic amyloidosis who presented with manifestations of GCA or PMR.     

Primary systemic amyloidosis with a retroperitoneal mass

A 73-year-old black woman presented with congestive heart failure, abdominal distension and ascites. A large retroperitoneal mass was demonstrated by gray-scale abdominal ultrasonography and confirmed by laparatomy and postmortem examination. This retroperitoneal mass consisted mainly of amyloid, as demonstrated by green birifringence with alkaline Congo red staining. Resistance of this staining pattern to permanganate treatment and the absence of inflammatory disease or malignancy at autopsy suggest the diagnosis of primary systemic amyloidosis. This is the first reported case of this disease manifesting as a retroperitoneal mass.     

Altered systemic ketone body metabolism in advanced heart failure

Heart failure is a systemic disease in which both myocardium and skeletal muscle exhibit alterations of energy metabolism. Failing myocardium exhibits impaired utilization of free fatty acids and glucose, which are major substrates for myocardial energy production. Ketone bodies normally provide a modest contribution to energy balance, but serum concentrations of ketone bodies are elevated in heart failure. To profile ketone body metabolism in advanced heart failure, we directly measured ketone body utilization by heart and skeletal muscle.Metabolite concentrations in arterial, coronary sinus, and central venous beds were measured to derive myocardial and skeletal-muscle ketone body utilization in 11 patients with advanced heart failure and 10 healthy control subjects who were undergoing electrophysiologic procedures. As expected, the mean myocardial arteriovenous oxygen difference was significantly increased in the heart-failure patients (8.3 ± 0.4 mL/dL, vs 7 ± 0.5 mL/dL in the control subjects; P = 0.05). Although the mean myocardial ketone body extraction ratio was relatively unchanged (0.49 ± 0.05 in heart-failure patients vs 0.54 ± 0.06 in control subjects, P = 0.53), skeletal-muscle ketone body utilization was markedly lower in the heart-failure patients (0.18 ± 0.06, vs 0.4 ± 0.04 in control subjects; P = 0.01).In this preliminary study, heart failure was associated with tissue-specific alteration of ketone body metabolism. In advanced heart failure, skeletal-muscle ketone body utilization was impaired, whereas myocardial ketone body utilization was preserved. Future studies are needed to determine whether ketone body metabolism serves as a dynamic quantitative biomarker of skeletal myopathy and fatigue in heart failure.