Primary amyloidosis--involving principally intrarenal blood vessels

We analysed renal biopsies from 34 nephrotic patients with renal amyloidosis, seven with primary form kappa chain (AL amyloidosis) and 27 with secondary amyloidosis associated with the other chronic diseases. Renal biopsy specimens were analysed using optical and immunofluorescence microscopy. The extent of amyloid deposits was graded from 0 to + + + +. Intrarenal blood vessel deposits were more prominent than intraglomerular in five of seven patients with AL amyloidosis, while they were identical in one, and in one, intraglomerular amyloid deposits were dominant. The results were different in the group of patients with secondary amyloidosis: a lower degree of intrarenal blood vessels deposition than glomerular was noted in 22 of 27 cases, the degree of deposition was identical in 4 of 27 cases and more expressed blood vessel deposition was present in only one case. Granular or combined deposits (granular+linear) were found on immunofluorescence microscopy in primary form, but the dominant form of deposition was amorphous in secondary amyloid.     

Amyloidosis in rheumatoid arthritis. A study of 48 histologically confirmed cases

In a group of 269 patients with rheumatoid arthritis histological examination demonstrated amyloidosis in 48 cases, viz. in 7 post mortem cases, in 28 rectal biopsies, in 12 renal biopsies and in one liver biopsy. Examination for amyloidosis was carried out in all patients who had proteinuria, otherwise in non-selected patients with definite rheumatoid arthritis. Even through rectal biopsy is a valuable screening method, it should not be overestimated, because in 12 patients with renal biopsy positive for amyloid, the foregoing rectal biopsies had been negative. According to our experience the most valuable method for diagnosis of amyloidosis in rheumatoid patients is renal biopsy, whereas synovial biopsy is the least conclusive. This paper, according to our knowledge, is the first report on observations of a regression of the inflammatory activity of rheumatoid arthritis and nephrotic syndrome as well as a complete morphological regression of amyloidosis.     

Diagnostic criteria of limited adenocarcinoma of the prostate on needle biopsy

Dialysis amyloidosis is one of the most incapacitating complications of long-term dialysis treatment. Quantitative assessment of amyloid deposition using radiolabelled tracers has been recently proposed but convincing evidence of its validity in uraemic patients remains to be provided. We studied the plasma kinetics of i.v. administered 125I-labelled serum amyloid P component (125I-SAP) in 20 chronic haemodialysis patients compared with those of nine healthy volunteers and three non-dialysed patients with systemic amyloidosis. Plasma clearance of the tracer was abnormal in 17 of 20 dialysis patients in whom plasma radioactivity declined in a bi-exponential mode, in contrast to the single-exponential slope observed in all healthy controls. 125I-SAP plasma half-life of the second component, probably reflecting metabolic clearance, was significantly prolonged in these dialysis patients compared with the healthy controls (35.3 versus 24.6 h, P < 0.001). Among the long-term haemodialysis patients the calculated extravascular distribution of 125I-SAP was significantly greater in those with severe arthropathy than in asymptomatic patients. These findings demonstrate for the first time that SAP clearance is disturbed in haemodialysis patients due to both failing renal elimination and retention in extravascular sites. The extravascular diffusion is greatly enhanced in patients with clinical evidence of amyloidosis. Therefore the study of plasma 125I-SAP kinetics promises to be a valuable tool to quantitate the extent of amyloidosis.     

Renal replacement therapy in multiple myeloma and systemic amyloidosis

Renal failure frequently complicates both multiple myeloma and systemic amyloidosis. Renal replacement therapy (RRT) may be poorly tolerated and its role in such patients is not clearly defined. Of fifty patients (26 males and 24 females) referred to a single centre because of renal failure associated with multiple myeloma or systemic amyloidosis 37 progressed to end-stage renal failure and 30 of these patients received RRT. Nine patients have been treated by CAPD, 13 by haemodialysis, and 8 patients have required both forms of dialysis. Overall one year and two year survival rates were 66% and 57% respectively. The median duration on RRT was 7.5 months (range 1-96 months) with a 51% one year, and a 46% two year survival rate. Of 7 patients with amyloidosis who underwent renal transplantation, 3 died within 6 months of transplantation. Undiagnosed cardiac involvement contributed to this early mortality. We conclude that renal replacement therapy is appropriate for some patients with multiple myeloma and systemic amyloidosis who develop endstage renal failure. Careful assessment and selection of patients is necessary prior to renal transplantation.     

Long-term survival (10 years or more) in 30 patients with primary amyloidosis

The median survival in primary systemic (AL) amyloidosis is less than 18 months. No published series of patients with AL amyloidosis have reported survival of more than 10 years. The records of all Mayo Clinic patients with a diagnosis of AL amyloidosis between January 1, 1966 and March 1, 1987 were reviewed. Patients with secondary amyloidosis, familial amyloidosis, senile systemic amyloidosis, and localized amyloidosis were excluded. During the 21 years of the study, 841 patients with AL amyloidosis were seen. Of these, 29 were excluded because the diagnosis was made at autopsy, and 2 others were excluded because no follow-up data were available. Actuarial survival for the 810 patients was 51% at 1 year, 16% at 5 years, and 4.7% at 10 years. Thirty patients survived for 10 years or more after the histologic diagnosis of AL amyloidosis; all received alkylating-agent therapy. In 14 patients, the monoclonal protein disappeared from the serum or urine. Of 10 patients with nephrotic syndrome, 4 had an objective response. Congestive heart failure, older age, creatinine value of 2 mg/dL or more, bone marrow plasma cell value of 20% or more, platelet count of 500 x 10(9)/L or less, and the presence of peripheral neuropathy were underrepresented in the 10-year survivors and are unfavorable prognostic features. Five percent of patients with AL amyloidosis survived for 10 years or more.     

Allogeneic bone marrow transplantation for systemic AL amyloidosis

Low-intensity chemotherapy is ineffective in most patients with AL amyloidosis, probably because clinical benefit requires regression of the amyloid deposits, and this occurs only very gradually after the underlying plasma cell dyscrasia has been suppressed. We report the first successful allogeneic bone marrow transplant (allo-BMT) for AL amyloidosis, which after 3 years was associated with complete clinical recovery. This supports the idea that there may be a brief window of opportunity in patients with AL amyloidosis during which dose-intensive chemotherapy is feasible and most likely to produce clinical benefit.     

Feasibility of stent placement above the sphincter of Oddi ("inside-stent") for patients with malignant biliary obstruction

In three cases of primary pulmonary amyloidosis the chief complaint was hemosputum. The diagnosis of amyloidosis was made using histochemical analysis of bronchial wall biopsy in all cases; multiple nodular lesions were observed in trachea and bronchi on flexible fiberoptic bronchoscopy. The surface of the tracheobronchial mucosa was smooth but bled easily. In one patient, chest X-ray film showed a solitary nodular shadow in the left lower lung field. These three cases were tracheobronchial amyloidosis, and one case was combined with nodular parenchymal type amyloidosis.     

Primary systemic amyloidosis with delayed progression to multiple myeloma

BACKGROUND: Primary systemic amyloidosis (AL) and multiple myeloma both are clonal plasma cell proliferative disorders. Although 10-15% of patients with myeloma have coexisting primary amyloidosis, it is unusual for patients with primary amyloidosis to progress to myeloma at a later date. The authors describe a case series of six patients in whom such progression occurred. METHODS: A computerized search was done of the medical records of all patients seen at the Mayo Clinic between January 1, 1960 and December 31, 1994 with a diagnosis of AL. Of 1596 patients with AL, 6 patients (age range, 60-74 years; median age, 68 years) with biopsy-proven AL were reviewed in whom delayed (at least 6 months after the diagnosis of AL) progression to multiple myeloma occurred. RESULTS: At the time of the diagnosis of AL, none of the six patients had evidence of multiple myeloma. The dominant manifestation of AL was peripheral neuropathy in three patients and cutaneous AL, renal AL, and amyloid arthropathy in one patient each. The diagnosis of multiple myeloma was made 10-81 months after the diagnosis of AL, based on the demonstration of multiple osteolytic lesions (4 patients) or marked bone marrow infiltration (> or = 50%) by plasma cells (5 patients). Two patients had received chemotherapy (melphalan and prednisone) for AL. Five patients received chemotherapy (four patients) or high dose methylprednisolone (one patient) after the diagnosis of multiple myeloma. Five patients died, and the median actuarial survival after the diagnosis of multiple myeloma was 20 months. Multiple myeloma was the cause of death in four patients; one patient died of systemic amyloidosis. In 2 patients death occurred within 3 months. CONCLUSIONS: AL occasionally progresses to overt multiple myeloma. These cases usually occur in patients without significant cardiac or hepatic AL who live long enough to develop multiple myeloma.     

Systemic amyloidosis in cystic fibrosis

We report two siblings with cystic fibrosis and systemic amyloidosis. The major clinical problem in both cases was recurrent respiratory infection with pulmonary fibrosis and bronchiectasis prior to death at ages 20 and 22 years. Findings from postmortem examinations disclosed diffuse amyloidosis. In addition, amyloid infiltration developed in both patients, with enlargement of the thyroid gland, and one required thyroidectomy. An autopsy review of 17 additional cases of cystic fibrosis failed to disclose any other instances of systemic amyloidosis.     

Few patients with "chronic prostatitis" have significant bladder outlet obstruction

Apolipoprotein E (apoE) is one of the amyloid associated proteins that is found in the amyloid plaque of Alzheimer's disease and systemic amyloidosis. ApoE might play an important part in the etiology of Alzheimer's disease by functioning as a "pathologic chaperone" to promote the formation of amyloid filaments. In this study, we investigated whether apoE is associated with amyloid deposits of primary localized cutaneous amyloidosis using immunohistochemistry, immunogold electron microscopy, and immunoblotting. The subjects consisted of 12 patients with lichen amyloidosus and one patient with macular amyloidosis. Light microscopically, amyloid deposits in the dermal papillae were round in shape and stained with Congo red. Immunohistochemically, apoE was detected in amyloid deposits in all the cases examined. Immunogold electron microscopy showed apoE immunoreactivity on the amyloid deposition. Immunoblots of amyloid-positive skin showed 35K and 14K proteins, which were taken to be apoE and its fragment, respectively. In normal skin extract, only the 35K protein was detected by the anti-human apoE. Moreover, the intensity of the amyloid-positive skin sample was stronger than that of the normal skin sample. Monoclonal anti-cytokeratin antibody reacted with the 45K protein of the amyloid-positive skin extract. These results indicate that apoE is a component of primary localized cutaneous amyloidosis, and that it might play an important role in primary localized cutaneous amyloidosis.     

Renal vein thrombosis as the major cause of renal failure in familial Mediterranean fever

Eighteen out of 57 patients (31-6 per cent) suffering from Familial Mediterranean Fever (FMF) were found to have the nephrotic syndrome, histologically proven amyloidosis and progressive renal failure. In 14 cases renal function deteriorated rapidly after the first appearance of significant proteinuria, and 12 cases (66-7 per cent) required regular haemodialysis. Seven of these patients, seen in the early stages of renal impairment, were subsequently diagnosed clinically as probably having developed renal vein thrombosis. There was radiological proof of intrarenal or major renal vein occlusion in five which in one patient progressed to inferior vena cave obstruction. Treatment with heparin, plasminogen activators and fibrinogenolytic agents was disappointing although renal function has stabilized in one patient on long term oral anticoagulant therapy. It is suggested that renal vein thrombosis is common in FMF with renal amyloidosis and usually causes rapid deterioration of function and irreversible renal failure requiring dialysis. Renal phlebography may delineate clot in the main renal veins or indicate areas of reduced blood flow due to thromboses in intrarenal venules. Treatment is only partially satisfactory but there is some evidence to suggest that renal phlebography should be undertaken promptly when renal function begins to fall followed by anticoagulant therapy to prevent further thromboembolic complications.     

Pathological changes in the formation of Helicobacter pylori-induced gastric lesions in Mongolian gerbils

OBJECTIVES: We investigated the expression of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) and their genes in the hearts of patients with cardiac amyloidosis and those with isolated atrial amyloidosis. BACKGROUND: The expression of ANP and BNP is augmented in the ventricles of failing or hypertrophied hearts, or both. The expression of ANP and BNP in the ventricles of hearts with cardiac amyloidosis, which is hemodynamically similar to restrictive cardiomyopathy, is not yet known. ANP is the precursor protein of isolated atrial amyloid. METHODS: We analyzed the immunohistocytochemical localizations of ANP and BNP as well as the expression of their mRNAs by in situ hybridization in the myocardium and measured the plasma levels of ANP and BNP in patients with cardiac amyloidosis. RESULTS: Four of the five right and all six left ventricular endomyocardial biopsy specimens obtained from six patients with cardiac amyloidosis were immunohistochemically positive for both ANP and BNP; none of the biopsy specimens from eight normal subjects were positive for ANP or BNP. All four of the right atria obtained at operation showed positive immunoreactions for both peptides. Electron microscopy identified specific secretory granules in ventricular myocytes of the patients with cardiac amyloidosis, but not in ventricular myocytes from the normal control subjects. Double immunocytochemical analysis revealed the co-localization of ANP and BNP in the same granules and that isolated atrial amyloid fibrils were immunoreactive for ANP and BNP, whereas ventricular amyloid fibrils were negative for both peptides. Both ANP mRNA and BNP mRNA were expressed in the ventricles of the patients with cardiac amyloidosis but not in the normal ventricles. The autopsy study of four patients with cardiac amyloidosis revealed an almost transmural distribution of ANP and BNP, with predominance in the endocardial side. Plasma BNP levels in the patients were markedly elevated ([mean +/- SD] 1,165.1+/-561.2 pg/ml) compared with those in the control subjects (8.9+/-6.0 pg/ml, p < 0.05). CONCLUSIONS: Expression of ANP and BNP and their genes was augmented in the ventricular myocytes of the patients with cardiac amyloidosis. Both regional mechanical stress by amyloid deposits and hemodynamic stress by diastolic dysfunction may be responsible for the expression of the peptides in patients with cardiac amyloidosis.     

Laboratory findings and serum levels of amyloid A and soluble interleukin-2 receptors in patients with renal amyloidosis

BACKGROUND: Renal amyloid involvement results either from primary or secondary amyloidosis. Extent of amyloid tissue deposition in kidneys and clinical course depends not only on the type of basic process but reflects also time of diagnosis and possibility to influence the basic process. METHODS AND RESULTS: We analyzed laboratory and clinical data of patients with bioptically proven renal amyloidosis. We found renal amyloidosis in 27 patients from an overall number of 750 renal biopsies (RB) performed in our department (i.e. 3.6%). AA amyloidosis was diagnosed in 16 pts, AL amyloidosis in 11 pts. About 50% of patients had laboratory signs of nephrotic syndrome, all patients had various degree of proteinuria. Impaired renal function were found in more than 50% of patients, in 6 of them we had to start renal replacement therapy. 8 pts died. Complications of severe nephrotic syndrome were the causes of death in majority of cases. We have started investigation of some amyloid precursors and cytokines in patients with AA and AL amyloidosis. We compared the results with group of patients with vasculitis. We investigated plasma and urinary levels of SAA (serum AA) and soluble receptor for interleukin 2 (sIL-2R). CONCLUSIONS: Clinical features and laboratory findings in our patients with renal amyloidosis approximately are in accordance with literary data. Plasmatic level of SAA was increased not only in the group of patients with AA amyloidosis, but also in the group of vasculitis. Urinary sIL-2R was significantly increased in patients with AA amyloidosis in comparison with healthy controls.     

Intractable diarrhoea associated with secondary amyloidosis in rheumatoid arthritis

OBJECTIVE: To examine the clinical characteristics of intractable diarrhoea associated with secondary amyloidosis in rheumatoid arthritis (RA). METHODS: Of 179 RA patients with biopsy confirmed secondary amyloidosis, 24 cases (23 women and one man) with intractable diarrhoea lasting for more than one month were retrospectively evaluated. RESULTS: The mean (SD) duration of diarrhoea was 87 (64) days. Prodromal symptoms of gastrointestinal dysfunction (n = 21) and impaired peristalsis (n = 16) were observed. Laboratory data showed hypoproteinaemia (4.7 (0.85) g/dl) caused by malabsorption or protein loss and high values of C reactive protein (17.0 (9.3) mg/dl). Recurrence of intractable diarrhoea (n = 4) and transition from intractable diarrhoea to other gastrointestinal problems of amyloidosis (ischaemic colitis (n = 2) and intestinal pseudo-obstruction (n = 4)) were observed. In 19 patients (25 episodes) the duration of intravenous hyperalimentation at remission (18 episodes) was 68 (52) days. Corticosteroid pulse therapy was administered to 10 patients (11 times) and the time elapsed from the end of corticosteroid pulse therapy to the end of diarrhoea was 18 (14) days. One and five year survival rates after the onset of intractable diarrhoea were 73.4% and 38.9%. Seven of 13 patients (54%) had died as a result of infectious diseases. CONCLUSION: Intractable diarrhoea associated with secondary amyloidosis in RA is a serious clinical entity and the prognosis is poor. Although it is assumed that intravenous hyperalimentation treatment and corticosteroid pulse therapy are favourable regimens for intractable diarrhoea, the patients should be monitored for possible infectious complications.     

Serum amyloid P component scintigraphy and turnover studies for diagnosis and quantitative monitoring of AA amyloidosis in juvenile rheumatoid arthritis

OBJECTIVE: To evaluate aspects of the natural history of AA amyloidosis complicating juvenile rheumatoid arthritis (JRA), and its response to therapy with chlorambucil. METHODS: Scintigraphy and 7-day turnover studies were performed in JRA patients with histologically proven (n = 35) or clinically suspected (n = 30) AA amyloidosis, following intravenous injection of 123I and 125I-labeled serum amyloid P component (SAP). Prospective monitoring studies were performed over 2-3 years in 20 patients with amyloidosis. All but 2 amyloidosis patients were treated with chlorambucil. RESULTS: Positive scanning results were obtained in all patients in whom imaging was performed within 12 years of positive biopsy findings of amyloid and in 5 patients with clinically suspected amyloidosis. Negative scanning results with normal SAP metabolism, indicating regression of amyloid, were obtained in 4 patients whose amyloidosis had been in full clinical remission for more than 12 years. Prospective monitoring studies in patients whose JRA-associated inflammatory activity was in remission demonstrated regression of amyloid in 8 patients and no substantial changes in 8 others; however, in 4 further patients with active inflammation, there was accumulation of amyloid. There was a very poor correlation between the amount of amyloid present at a particular site and the resultant organ dysfunction. CONCLUSION: Radiolabeled SAP scintigraphy and turnover studies are useful complementary tools in the diagnosis, screening, and quantitative monitoring of type AA amyloidosis in JRA. The amyloid deposits may progress and/or regress at different rates in different anatomic sites over short periods.     

Localized amyloidosis of the seminal vesicle. Possible association with hormonally treated prostatic adenocarcinoma

OBJECTIVE: Localized seminal vesicle amyloidosis is an unusual finding in surgical pathology material. Previous studies have demonstrated that the amyloid is directly produced by the seminal vesicle epithelial cells. We investigated the possible association of seminal vesicle amyloid in patients hormonally treated for prostate carcinoma. METHODS: Cases were collected from over 200 prostate needle biopsies, seminal vesicle biopsies, and prostatectomy specimens from the surgical pathology files at The Mount Sinai Hospital, New York, NY. None of the patients with seminal vesicle amyloidosis had a chronic inflammatory disorder, serum or urine protein abnormalities, or other identifiable masses. RESULTS: Six cases of localized seminal vesicle amyloidosis were found in the surgical pathology material examined. Five of the six cases had prostatic carcinoma, and one case was seen in a biopsy for benign prostatic hyperplasia. Four of the five carcinoma cases had prior hormonal treatment (luteinizing hormone-releasing hormone agonist with an antiandrogen agent, and one patient, in addition, had received radiotherapy). The amyloid deposits were limited to the seminal vesicle lamina propria without involvement of vascular walls. The amyloid reacted with Congo red staining that was sensitive to potassium permanganate. Immunohistochemically, all cases were negative for AA amyloid, beta 2-microglobulin, and kappa and lambda light chains. CONCLUSION: We raise the possibility that in some instances, prior hormonal therapy may act as a seminal vesicle epithelial stimulant for the elaboration of this protein.     

Diagnosis and treatment of postoperative chyle leakage via percutaneous transabdominal catheterization of the cisterna chyli: a preliminary study

BACKGROUND AND AIMS: The liver is frequently involved in amyloidosis but the significance of hepatic amyloid has not been systematically studied. We have previously developed scintigraphy with 123I serum amyloid P component (123I-SAP) to identify and monitor amyloid deposits quantitatively in vivo and we report here our findings in hepatic amyloidosis. METHODS: Between 1988 and 1995, 805 patients with clinically suspected or biopsy proven systemic amyloidosis were evaluated. One hundred and thirty eight patients had AA amyloidosis, 180 had AL amyloidosis, 99 had hereditary amyloid syndromes, and 67 had dialysis related (beta 2 microglobulin) amyloid. One hundred and ninety two patients with amyloidosis were followed for six months to eight years. RESULTS: Hepatic amyloid was found in 98/180 (54%) AL and 25/138 (18%) AA patients but in only 1/53 patients with familial transthyretin amyloid polyneuropathy and in none with dialysis related amyloidosis. There was complete concordance between hepatic SAP scintigraphy and the presence or absence of parenchymal amyloid deposits on liver histology. Amyloidosis was never confined to the liver. Mortality was rarely due to hepatic failure, although hepatic involvement with AA amyloid carried a poor prognosis. Successful therapy to reduce the supply of amyloid fibril protein precursors was followed by substantial regression of all types of amyloid. CONCLUSIONS: SAP scintigraphy is a specific and sensitive method for detecting and monitoring hepatic amyloid. Liver involvement is always associated with major amyloid in other organ systems and carries a poor prognosis in AA type. Appropriate therapy may substantially improve prognosis in many patients.     

"Benign" monoclonal gammopathy--after 20 to 35 years of follow-up

All 241 patients with an apparently benign monoclonal gammopathy who were examined at the Mayo Clinic before Jan. 1, 1971, underwent prospective follow-up for 20 to 35 years (median, 22 years). Electrophoresis and immunoelectrophoresis of serum and urine specimens were performed periodically in an effort to determine the frequency of development of multiple myeloma, primary amyloidosis, macroglobulinemia, or other lymphoproliferative diseases. At follow-up, the patients were categorized into one of four groups: group 1 (benign)--46 patients (19%) who were alive and had a benign monoclonal gammopathy; group 2--23 patients (10%) who had a serum monoclonal protein value of 3 g/dl or more but did not require chemotherapy; group 3--113 patients (47%) who died without evidence of myeloma or related disorders; and group 4-59 patients (24%) in whom multiple myeloma (39), systemic amyloidosis (8), macroglobulinemia (7), or a malignant lymphoproliferative disease (5) developed at a median of 10, 9, 8, and 10 1/2 years, respectively, after detection of the monoclonal protein. Thus, in patients with an apparently benign monoclonal gammopathy, follow-up must be continued indefinitely because multiple myeloma, amyloidosis, macroglobulinemia, or related disorders occur in approximately a fourth of them.     

Factors influencing outcome and length of stay in a stroke rehabilitation unit. Part 2. Comparison of 318 screened and 248 unscreened patients

Amyloidosis associated with Crohn's disease was found in 7 patients among 85 subjected to intestinal resection for granulomatous enterocolitis. Most of the patients had symptoms of inflammatory bowel disease of relatively short duration before the diagnosis of amyloidosis was made and were without suppurative complications. Systemic involvement was seen in 6 of the patients. One died postoperatively from renal failure, and in 2 other patients kidney transplantation was performed because of deterioration of a pre-existent renal insufficiency. Six patients were alive 6 months to 10 years after amyloidosis was diagnosed. There is great risk of rapid deterioration of kidney function postoperatively in these patients. However, our experience suggests that in some cases the progression of amyloidosis may be delayed or even brought to a halt after surgical treatment of Crohn's disease.     

Duration of pulmonary venous atrial reversal flow velocity and mitral inflow a wave: new measure of severity of cardiac amyloidosis

Transmitral Doppler flow patterns of patients with cardiac amyloidosis evolve from an early impaired relaxation to an advanced restrictive pattern. This reflects increasing severity of diastolic dysfunction and hence left ventricular filling pressures. The duration of the pulmonary venous atrial reversal flow was recently shown to exceed that of the mitral inflow A wave in patients with left ventricular end-diastolic pressure greater than 15 mm Hg. The objective of this study was to assess the utility of this index as a measure of the severity of cardiac amyloidosis. Comprehensive transthoracic 2-dimensional and pulsed-wave Doppler echocardiograms of the pulmonary venous and transmitral flows were made of 23 patients (10 women) with biopsy-proven diagnosis of primary systemic amyloidosis and of 49 subjects as age-matched normal controls. The amyloidosis group was divided into non-restrictive and restrictive subgroups on the basis of the patients' transmitral inflow deceleration time (>150 and < or =150 ms, respectively). The durations of the pulmonary venous atrial reversal and mitral inflow A wave were measured, and the differences between the flow durations were compared with the control and published data in the nonrestrictive and restrictive groups. The mean duration of the pulmonary venous atrial reversal was significantly longer in the amyloid than the control group (P < .01). The mean duration of the mitral inflow A wave was significantly shorter in the restrictive group than both the nonrestrictive and the control groups (P < .05). The duration of the pulmonary venous atrial reversal exceeded that of the mitral inflow A wave in all patients with cardiac amyloidosis. The difference in duration between pulmonary venous atrial reversal and mitral inflow A wave was significantly greater in the amyloidosis group compared with the normal group, and this index varied significantly within the amyloid group between the abnormal relaxation and the restrictive groups. The difference in the duration between the pulmonary venous atrial reversal and the mitral inflow A wave is a reliable index of diastolic function and can be used to assess the severity of cardiac amyloidosis.