Alan Rubinow

Sensitivity and specificity of the echocardiographic features of cardiac amyloidosis

Thirty-one patients with documented cardiac amyloidosis were compared to 39 control subjects with left ventricular hypertrophy to determine specific 2-dimensional echocardiographic features of amyloid. In 16 patients, increased myocardial echogenicity was present when a single short-axis view was examined, and had a sensitivity of 63% and a specificity of 74% for the diagnosis of amyloidosis. When complete echocardiograms were reviewed (15 patients), an improved sensitivity of 87% and specificity of 81% based on increased echogenicity was seen. Increased atrial septal thickness was present in 60% of amyloid patients and no controls. The combination of increased myocardial echogenicity and increased atrial thickness was 60% sensitive and 100% specific for the diagnosis of amyloidosis. The ratio of electrocardiographic voltage (S in V1 + R in V5 or V6) to left ventricular cross-sectional area also was examined. A ratio of less than 1.5 was 82% sensitive and 83% specific for amyloid (excluding the 2 patients with left bundle branch block), but added little to the diagnosis as determined from the 2-dimensional echocardiogram.

Skin Involvement in Generalized Amyloidosis: A Study of Clinically Involved and Uninvolved Skin in 50 Patients with Primary and Secondary Amyloidosis

A punch or excisional biopsy of the skin was done in 50 patients with generalized amyloidosis: In 46, clinically normal skin, usually the forearm, was biopsied and in four, only cutaneous lesions. Amyloid was seen in the skin of 21 of 38 patients with primary and multiple myeloma-associated amyloidosis. Sixteen of 34 biopsies from clinically uninvolved skin were positive. Five of 12 patients with secondary amyloidosis had amyloid deposits in clinically normal skin. Overall, amyloidosis was definitively diagnosed on skin biopsy examination in 26 patients. A punch biopsy of clinically involved or uninvolved skin is an innocuous, simple procedure with a high diagnostic yield and can be done in an office setting.

Cardiac arrhythmias in systemic amyloidosis: correlation with echocardiographic abnormalities

To determine the prevalence of cardiac arrhythmias in patients with systemic amyloidosis 24 hour electrocardiographic monitoring was performed in 27 patients with primary amyloidosis and in 6 patients with familial amyloid polyneuropathy. All patients underwent echocardiographic studies. Despite a high prevalence of conduction disturbances on standard electrocardiogram, clinically significant bradyarrhythmias were rare (one patient). Complex ventricular arrhythmias (multiform, paired or repetitive beats) occurred in 14 patients (47%) with primary amyloid and 3 patients (50%) with familial amyloid polyneuropathy. The presence of cardiac arrhythmia correlated with heart failure and, more strongly, with an abnormal echocardiogram. There were four sudden deaths, all in patients with abnormal echocardiograms and complex ventricular arrhythmias. These findings suggest that complex ventricular arrhythmia on Holter monitoring is common in cardiac amyloidosis and may be a harbinger of subsequent sudden cardiac death.

Survival of patients with primary (AL) amyloidosis: Colchicine-treated cases from 1976 to 1983 compared with cases seen in previous years (1961 to 1973)☆

Primary amyloidosis has a variable course, but is generally associated with a short life expectancy. To date, no specific therapy has been available. Fifty-three patients with AL amyloidosis seen between 1976 and 1983 were treated with colchicine, and their clinical course and survival were compared with that in 29 other patients seen between 1961 and 1973. Of the variables measured, the treatment, the patients sex, and the time interval from diagnosis to referral of treatment were significantly associated with length of survival. Median survival for the colchicine-treated patients was 17 months, compared with six months for the non-colchicine-treated patients. A surprising finding was the longer life span in female patients (median eight months versus four and a half months in the non-colchicine-treated group, and 25.5 months versus 10 month in the colchicine-treated group). The study suggests that colchicine has improved the life expectancy in AL amyloidosis. Although it is not a specific therapy, it may be a reasonable form of adjunctive treatment in this complex disorder.

Sensitivity of technetium-99m-pyrophosphate scintigraphy in diagnosing cardiac amyloidosis

To determine the value of technetium-99m-pyrophosphate myocardial scintigraphy in the diagnosis of amyloid heart disease this procedure was prospectively performed in 20 consecutive patients with biopsy-proven primary amyloidosis. Eleven patients had echocardiographic abnormalities compatible with amyloid cardiomyopathy, 9 of whom had congestive heart failure. Diffuse myocardial pyrophosphate uptake was of equal or greater intensity than that of the ribs in 9 of the 11 patients with echocardiograms suggestive of amyloidosis, but in only 2 of the 9 with normal echocardiograms, despite abnormal electrocardiograms (p less than 0.01). Increased wall thickness measured by M-mode echocardiography correlated with myocardial pyrophosphate uptake (r = 0.68, p less than 0.01). None of 10 control patients with nonamyloid, nonischemic heart disease had a strongly positive myocardial pyrophosphate uptake. Thus, myocardial technetium-99m-pyrophosphate scanning is a sensitive and specific test for the diagnosis of cardiac amyloidosis in patients with congestive heart failure of obscure origin. It does not appear to be of value for the early detection of cardiac involvement in patients with known primary amyloidosis without echocardiographic abnormalities.

Severe intrahepatic cholestasis in primary amyloidosis: A report of four cases and a review of the literature

Abstract Liver involvement occurs frequently in patients with systemic amyloidosis, but jaundice is rare. The clinical and histopathologic features are described in four of 78 patients (5.3 per cent) with primary amyloidosis in whom severe intrahepatic cholestasis developed. The data on an additional eight patients recorded in the literature were reviewed. Criteria for inclusion were a tissue diagnosis of amyloidosis, a serum bilirubin level greater than 5 mg/100 ml, histopathologic evidence for cholestasis and no extrahepatic biliary obstruction. Hepatomegaly was present in 12 patients (100 per cent), ascites in nine (75 per cent) and pruritus in eight (67 per cent). The serum bilirubin ranged from 9 to 44 mg/100 ml, the serum alkaline phosphatase was markedly increased in 10 patients (83 per cent) and hypercholesterolemia occurred in seven (58 per cent). Microscopic examination of the liver revealed diffuse amyloid deposition and compression atrophy in 12 patients (100 per cent). The amyloid was prominent in the periportal regions, and some sparing of the centrilobular areas was observed. Bile thrombi and bilirubin staining of hepatocytes were predominantly in the centrilobular zones. Liver cell necrosis, fibrosis or nodularity was uncommon. The pathogenesis of intrahepatic cholestasis in these patients is probably related to the deposition of amyloid in a manner that interferes with the passage of bile from the canaliculi and/or the small intrahepatic bile ducts to the septal bile ducts. Obstructive jaundice carries a poor prognosis. Nine of 12 patients (75 per cent) died of renal failure three weeks to two months after the onset of jaundice. Amyloidosis should be considered in the patient with unexplained intrahepatic cholestasis, and liver tissue should be stained with Congo red and viewed under polarized microscopy.

Esophageal manometry in systemic amyloidosis: A study of 30 patients☆

The motility of the esophagus was studied by esophageal manometry in 24 patients with primary amyloidosis and six with secondary amyloidosis. Resting lower esophageal sphincter pressure was decreased in 12 patients with primary amyloidosis and two with secondary amyloidosis; 12 of these 14 patients complained of heartburn. Abnormalities in the motility of the body of the esophagus were found in nine patients with primary amyloidosis and one with secondary amyloidosis. No abnormality of the upper esophageal sphincter was demonstrated in any of the 30 patients. Six of the nine patients with primary amyloidosis exhibiting the most marked esophageal motor dysfunction had striking evidence of peripheral and/or autonomic nervous system involvement. No consistent pattern of motility disorder was observed in either group. The manometric abnormalities observed are consistent with a random deposition of amyloid in the esophagus involving a myopathic and/or neuropathic component.

Lowered Prealbumin Levels in Patients with Familial Amyloid Polyneuropathy (FAP) and Their Non-Affected But At Risk Relatives

Amyloid fibrils in familial amyloid polyneuropathy, the familial (AF) form of systemic amyloidosis, are composed of the monomeric unit (14,000 MW) of prealbumin molecules. By radioimmunoassay, the serum level of prealbumin was measured in 25 patients from 12 different kinships with this dominantly inherited form of amyloidosis and 56 unaffected, but at risk, relatives from two of the kinships. Results were compared to prealbumin levels in normal individuals and patients with primary (AL) and secondary (AA) forms of systemic amyloidosis. Significantly lowered prealbumin levels were found in the AF patients (149.2 ug/ ml) and their at risk relatives (169.0 ug/ml) when compared to normal individuals (232.9 ug/ml), AL patients (221.9 ug/ml) and AA patients (211.7 ug/ml). No abnormality was found in levels of retinol binding protein (RBP), which is carried by prealbumin, in the serum of either the AF patients or their relatives. The depressed prealbumin levels may indicate a structural variant molecular form, an extra hepatic synthesis or an abnormality in catabolism of this protein that is present prior to the clinical or histopathologic onset of the AF disease.

Familial amyloid polyneuropathy. Demonstration of prealbumin in a kinship of german/english ancestry with onset in the seventh decade

A family with autosomal dominant transmitted familial amyloid polyneuropathy residing in Texas is described. Clinically, the prominent sensory and severe autonomic nervous system involvement resembles the Andrade (Portuguese) type I familial amyloid polyneuropathy but is unique in that the age of onset is in the seventh decade in all family members affected to date. Using an immunoperoxidase technique, prealbumin was demonstrated in the amyloid deposits. This finding suggests that this family shares biochemical as well as clinical characteristics consistent with similar kinships with type I familial amyloid polyneuropathy of diverse geographic origin.

Primary (AL) amyloidosis as a cause of breast masses

Amyloidosis is rarely considered in the differential diagnosis of breast masses. During the past six years, 27 women with primary (24) and multiple myeloma-associated (three) amyloidosis (AL amyloid) were evaluated at our center. In five of these patients, amyloid was demonstrated on microscopic examination of breast tissue. The clinical presentations were similar to fibrocystic breast disease in two cases and malignancy in two others. Amyloidosis of the breast may be more common than previously recognized, especially considering the predilection of amyloid for depositing around fat cells. Therefore, pathologic examination of nonmalignant breast tissue should include Congo red staining and viewing under polarized light.