Functional hypothalamic amenorrhoea: leptin treatment, dietary intervention and counselling as alternatives to traditional practice - systematic review.

Functional hypothalamic amenorrhoea (FHA) is a neuroendocrine disorder caused by an energy deficit and characterized by low leptin levels. Based on this, previous studies have suggested that leptin administration may play a crucial role in FHA treatment. However, FHA is also associated with abnormal psychosocial and dietary behaviour that needs to be addressed. In this context, this systematic review examined the efficacy of leptin treatment, non-pharmacological therapy and nutritional interventions in FHA. PubMed, Medline and Cochrane Library databases were searched in order to find relevant papers, including randomized controlled trials, clinical trials, prospective studies and case reports. The effects of different treatments on reproductive function, hormonal status and bone markers were recorded. Studies regarding other forms of treatment were excluded. In total, 111 papers were retrieved. After the removal of 29 duplicate papers, the abstracts and titles of 82 papers were examined. Subsequently, 53 papers were excluded based on title, and seven papers were omitted based on abstract. The remaining 11 papers were used: three based on leptin treatment, three regarding non-pharmacological treatment and five regarding dietary intervention. This literature review indicates that all of these treatment strategies improved reproductive function and hormonal status significantly, although conclusive results could not be drawn on bone markers. While leptin may be a promising new treatment, social aspects of FHA should also be addressed. As a result, a multifaceted therapeutic approach should be applied to treat affected women.

Diagnostic accuracy of a home blood pressure monitor to detect atrial fibrillation.

Atrial fibrillation (AF) is the most common sustained arrhythmia and is associated with an increased long-term risk of stroke. A screening test for early diagnosis has the potential to prevent AF-related strokes. This study assessed the diagnostic accuracy of an automated device for self-home blood pressure (BP) monitoring, which implements an algorithm for AF detection. A modified, automated oscillometric device for self-home BP monitoring (Microlife BPA100 Plus, Microlife, Heerbrugg, Switzerland) with an AF detector was used to carry out triplicate BP measurements in subjects with sinus rhythm, AF and non-AF arrhythmias. During each BP measurement, the electrocardiogram (ECG) was recorded simultaneously. A total of 217 simultaneous BP measurements and ECG recordings were obtained from 73 subjects. Twenty-seven subjects (37%) had AF, 23 (31%) non-AF arrhythmias and 23 (31%) had sinus rhythm. A single measurement had 93% sensitivity and 89% specificity for detecting AF. For two measurements, in which one of them was required to detect AF, the sensitivity was 100% and specificity 76%, whereas for three measurements, in which two of them were required to detect AF, the sensitivity was 100% and specificity 89% (kappa=0.86 for an agreement with ECG). Using the latter approach, there were five false positive cases all having irregularities in approximately 50% of the heartbeats. In patients with tachyarrhythmia, the device underestimated heart rate. These data suggest that an electronic device for self-home BP monitoring, which implements an algorithm for AF diagnosis has an excellent diagnostic accuracy and might, therefore, be used as a reliable screening test for the early diagnosis.

The effects of enalapril on p53 expression in left ventricular cardiomyocytes after aortic stenosis.

ACE-inhibitors prevent the development of left ventricular hypertrophy (LVH). The tumor suppressor gene p53 up-regulates the cellular renin-angiotensin system, resulting in ANG II synthesis, which activates p53 creating a positive feedback loop. One hundred and fourteen rabbits were separated into groups A (control), B (sham-operated), C and D. In groups C and D, an aortic stenosis was performed, and in group D the animals were treated with enalapril. For p53 determination, LV specimens were examined by Western blot analysis and an immunohistochemical study was performed, except for samples from group D. In conclusion, LVH was significantly induced at 7 and 28 days after aortic stenosis with no difference between the two periods, while enalapril prevented hypertrophy in these two groups. p53 was transcriptionally activated and immunoreactively present after acute pressure overload as well as in the sham-operated group. Enalapril decreased the p53 expression at 180 min, 7 and 28 days following aortic stenosis.

Assessment of the left ventricular diastolic reserve in essential hypertension: the acute saline load test.

OBJECTIVE: The aim of this study was to evaluate the significance of the development of a restrictive response to an acute saline load, defined as an increase in the ratio of peak early to peak late diastolic transmitral flow velocity (E/A ratio) associated with a decrease in the deceleration time, in patients with mild to moderate untreated hypertension. BACKGROUND: Recognised abnormal patterns of transmitral diastolic flow include, from 'best' to 'worst': prolonged relaxation, pseudonormalisation, and restrictive physiology. The common denominator of these transitions is the constellation of an increase in the E/A ratio associated with a decrease in deceleration time. PATIENTS AND METHODS: Sixteen normal control subjects (6 males, 10 females, age 51.6 +/- 6.9 years) and 24 patients with mild to moderate untreated hypertension (12 males, 12 females, age 46.8 +/- 7.5 years) underwent supine blood pressure measurement with sphygmomanometry, biochemical studies, and transthoracic M-mode, 2D, and Doppler echocardiography before and after an acute saline load (7 mL kg(-1), maximum 500 mL, NaCl 0.9% within 15 min IV). RESULTS: The baseline E/A ratio was lower (0.90 +/- 0.14 vs. 1.04 +/- 0.18; P < 0.01) and the deceleration time was longer (158.8 +/- 19.4 vs. 135 +/- 8.9 ms; P < 0.01) in patients with hypertension compared with normotensive controls. However, no patient with hypertension exhibited a transmitral flow velocity pattern compatible with typical prolonged relaxation. A restrictive response to the acute saline load was observed in 12 (50%) of the hypertensive and none of the control subjects. Hypertensive patients with a restrictive response to the acute saline load had a lower baseline E velocity (54.8 +/- 8.7 cm s(-1) vs. 66 +/- 6.4 cm s(-1); P = 0.003), a lower baseline E/A ratio (0.83 +/- 0.13 vs. 0.97 +/- 0.12; P = 0.015), and a longer deceleration time (167.5 +/- 15.4 ms vs. 150 +/- 19.5; P = 0.03) than hypertensive patients without such a response. CONCLUSION: A restrictive response to an acute saline load is indicative of a limited diastolic reserve in patients with mild to moderate untreated hypertension. Further studies are required in order to evaluate the significance of such a response with regards to risk stratification and efficacy of medical treatment in this patient population.

Pulmonary capillary endothelial dysfunction in early systemic sclerosis.

OBJECTIVE: Pulmonary capillary endothelium-bound angiotensin-converting enzyme (PCEB-ACE) activity is a sensitive and quantifiable index of endothelial function in vivo. Systemic sclerosis (SSc) is characterized by endothelial damage and excess collagen formation, causing mainly pulmonary hypertension (PH) in the limited cutaneous SSc (lcSSc) subset and interstitial lung disease with pulmonary interstitial fibrosis (PIF) in the diffuse cutaneous SSc (dcSSc) subset. This study was undertaken to investigate the hypothesis that PCEB-ACE activity is reduced early in SSc, in the absence of PH or PIF. METHODS: Applying indicator-dilution techniques, we measured single-pass transpulmonary hydrolysis and percent metabolism (%M) of a synthetic ACE substrate and calculated functional capillary surface area (FCSA) in 25 SSc patients and 11 controls. Substrate hydrolysis and %M reflect ACE activity per capillary; FCSA reflects ACE activity per vascular bed. RESULTS: PCEB-ACE activity was decreased in both SSc subsets. Among patients without PH, substrate hydrolysis and %M were decreased in patients with lcSSc and more profoundly in those with dcSSc; loss of FCSA normalized to body surface area (FCSA/BSA) was observed in dcSSc, but not in lcSSc. High-resolution computed tomography of the lung, performed in all SSc patients, revealed no correlation between substrate %M, hydrolysis, or FCSA/BSA and the degree of PIF; 5 dcSSc and 5 lcSSc patients with no detectable PIF exhibited decreases in hydrolysis and %M, while FCSA/BSA was decreased only in dcSSc. CONCLUSION: Depression of PCEB-ACE activity, indicating pulmonary endothelial dysfunction, occurs early in SSc, in the absence of PH or PIF, and is more pronounced, at this early pulmonary disease stage, in dcSSc than in lcSSc.

Right ventricular diastolic dysfunction in patients with anticardiolipin antibodies and antiphospholipid syndrome.

OBJECTIVE: To evaluate the prevalence of diastolic dysfunction in patients with anticardiolipin antibodies (aCL) and to examine whether the antiphospholipid syndrome (APS) is associated with diastolic dysfunction independently of valvular abnormalities and systolic dysfunction. METHODS: Pulsed, continuous, colour Doppler echocardiography was performed in 179 subjects, of whom 15 were excluded from the analysis because of systolic dysfunction or severe valvular disease. The remaining 164 subjects included 29 patients with primary APS, 26 patients with secondary APS (APS in the presence of systemic lupus erythematosus (SLE)), and 30 patients with SLE and aCL but without APS; 43 patients with SLE without aCL and 36 normal volunteers served as control groups. RESULTS: The groups compared differed significantly in all measures of right ventricular function. There was a gradation of increasing diastolic function impairment as manifested by prolonged deceleration time (DT) and isovolumic relaxation time (IVRT) across the groups of patients with SLE without aCL, SLE with aCL, secondary APS, and primary APS. Differences in left ventricular diastolic function measures were less prominent. In regression analysis, DT increased by 19.6 ms (p=0.002) in the presence of primary APS and by 20.1 ms (p=0.038) in the presence of pulmonary hypertension. The titre of IgG aCL was the strongest predictor of a prolonged IVRT. CONCLUSION: Diastolic dysfunction, in particular of the right ventricle-that is, independent of valvular disease and systolic dysfunction, is a prominent feature of APS and may be related to the pathogenesis of the syndrome.

ACE/DD genotype is associated with hemostasis balance disturbances reflecting hypercoagulability and endothelial dysfunction in patients with untreated hypertension.

BACKGROUND: Angiotensin-converting enzyme (ACE) gene polymorphism has been associated with an increased incidence of myocardial infarction. Recent studies have investigated a potential influence of ACE gene polymorphism on fibrinolysis or endothelial function. It has been previously established that essential hypertension is accompanied by endothelial dysfunction and fibrinolytic balance disorders. The aim of our study was to study the relation between ACE gene polymorphism and fibrinolytic/hemostatic factors as well as endothelial cell damage markers in patients with hypertension. METHODS: The following parameters were evaluated in 104 patients with previously untreated hypertension: plasminogen activator inhibitor-1 (PAI-1), tissue plasminogen activator (tPA) antigen, fibrinogen, D-dimer, and von Willebrand factor (vWF). The genotype of the ACE gene was also determined (by the polymerase chain reaction method), and patients were characterized according to the observed alleles as deletion/deletion (DD), insertion/insertion (II), or insertion/deletion (ID). RESULTS: Those with DD genotype (n = 42) had significantly higher plasma levels of PAI-1 antigen (P =. 012), tPA antigen (P =.0001), fibrinogen (P =.0002), D-dimer (P =. 0001) and vWF (P =.0004) compared with ID (n = 30) or II (n = 32) genotypes. The ACE gene genotypes appeared to be significant predictors for plasma PAI-1 antigen, tPA antigen, fibrinogen, D -dimer, and vWF even after adjustment for age, sex, body mass index, triglyceride and cholesterol levels, and blood pressure. CONCLUSIONS: Our findings suggest that the ACE/DD genotype is associated with hemostasis balance disturbances reflecting hypercoagulability and endothelial damage in patients with untreated hypertension.

Predicting response to chronic antihypertensive treatment with fosinopril: the role of angiotensin-converting enzyme gene polymorphism.

Insertion (I)/deletion (D) polymorphism of the ACE gene has been reported to be involved in various cardiovascular diseases. We investigated prospectively whether the response to the ACE inhibitor fosinopril varied according to the ACE genotype in previously untreated Greek hypertensive patients. After a 4-week observation period, fosinopril was administered at a dose of 20 mg daily and blood pressure was measured weekly for 6 months. The study population consisted of 104 hypertensive patients (46 male, 58 female). There were no differences in age, gender, body mass index, and pretreatment blood pressure levels among patients with the DD, ID, and II genotypes (n= 42, 30, 32, respectively). The reduction in systolic blood pressure was significantly greater in patients carrying the DD compared to II or ID genotypes (5.6 +/- 3.1 vs. 3.1 +/- 1.1 or 3.6 +/- 2.2, respectively; ANOVA, p < 0.05). The reduction in diastolic blood pressure was also significantly greater in DD hypertensives compared with II or ID (8.9 +/- 6 vs. 5.5 +/- 3.4 or 5.8 +/- 4, respectively; ANOVA, p < 0.05). The age and BMI were not correlated with the changes in SBP or DBP that were observed after fosinopril administration. In conclusion, the ACE gene genotype was shown to influence the response to fosinopril in hypertensive patients.

Fibrinolytic/hemostatic variables in arterial hypertension: response to treatment with irbesartan or atenolol.

Essential hypertension is often accompanied by abnormalities of the coagulation/fibrinolytic system, predisposing to a procoagulant state. The aim of the present study was to compare the effects of atenolol (beta1-blocker agent) and irbesartan (angiotensin II type 1 receptor antagonist) on plasma levels of hemostatic/fibrinolytic and endothelial function markers in a cohort of previously untreated hypertensives. Fifty-four patients were randomly assigned to atenolol 25 to 150 mg (26 patients) or irbesartan 75 to 300 mg (28 patients). The plasma levels of plasminogen activator inhibitor-1 antigen, thrombomodulin, tissue factor pathway inhibitor antigen, fibrinogen, and factor XII were determined before and after 6 months of therapy. Age, gender distribution, body mass index, lipid profile, and baseline values of the measured markers were similar in both groups. Baseline values for systolic and diastolic blood pressure, as well as the reduction after treatment, were not significantly different between the two groups. Treatment with irbesartan was associated with a significant decrease in the levels of all the parameters. Similar findings were observed in the atenolol group, except for factor XII and tissue factor pathway inhibitor levels, which were not significantly decreased in this group. The reduction, however, of fibrinogen, plasminogen activator inhibitor-1, and thrombomodulin was significantly greater in the irbesartan than in the atenolol group. In conclusion, the results indicated that, despite an equally controlled blood pressure, 6-month therapy with irbesartan was associated with a more favorable modification of hemostatic/fibrinolytic status than atenolol.

Resistance to activated protein C and FV leiden mutation in patients with a history of acute myocardial infarction or primary hypertension.

This study was designed to investigate both resistance to activated protein C (APC-R) and the factor FV Q506 mutation incidence in patients with a history of acute myocardial infarction (AMI) and patients with primary hypertension (PH), a high-risk group for arterial thrombosis. Eighty patients with a history of AMI (group A), 160 patients with a history of PH (group B), and 124 age-matched controls without arterial disease (group C) were studied. APC-R was determined using the Coatest APC Resistance Kit of Chromagenix, Sweden. The prevalence of the FV Q506 mutation was estimated by DNA analysis (Bertina method). The prevalence of the FV Q506 mutation was 20%, 13.75%, and 8% in groups A, B, and C, respectively (A v C P = .0466). The prevalence of APC-R was 47.5% in group A v 13% in group C (P < .0001) and 36.25% in group B v 13% in group C (P < .0001). The response to activated protein C expressed as mean value +/- SD was 2.05 +/- 0.33 in group A v 2.56 +/- 0.46 in group C (P < .05) and 2 +/- 0.22 in group B v 2.56 +/- 0.46 in group C (P < .05). These findings suggest that patients with a history of AMI or PH have a significantly increased incidence of both APC-R and FV Q506 mutation compared with the control group. These findings support the hypothesis that these anticoagulant defects may be risk factors for arterial thrombosis.

Left atrial systolic function is depressed in idiopathic and preserved in ischemic dilated cardiomyopathy.

BACKGROUND: Left atrial systolic dysfunction, unexplained by altered loading conditions, has been reported in idiopathic dilated cardiomyopathy suggesting left atrial involvement in the myopathic process. MATERIALS AND METHODS: Seventeen patients with idiopathic dilated cardiomyopathy, 16 with ischemic dilated cardiomyopathy and 18 normal controls were studied with transthoracic echocardiography and cardiac catheterization. Transmitral diastolic flow was evaluated with pulsed Doppler. Left atrial volume (cm3/m2) at mitral valve opening (maximal, Vmax.), onset of atrial systole (P wave of the electrocardiogram, Vp), and mitral valve closure (minimal, Vmin. ) was determined with two-dimensional echocardiography using the biplane area-length method. The left atrial active emptying fraction (ACTEF = [Vp-Vmin.] x 100/Vp) served as an index of systolic function. RESULTS: The peak early diastolic transmitral flow velocity (cm/sec) was similar in the three groups (idiopathic: 60 +/- 16, ischemic: 58 +/- 20, control: 56 +/- 22; P = NS), whereas the late diastolic transmitral flow velocity was lower but not significantly different in idiopathic compared to ischemic cardiomyopathy, and in both was lower than control (26 +/- 12 vs. 34 +/- 13 vs. 44 +/- 14, respectively; P < 0.05). Vmax. and Vp were similar in idiopathic and ischemic cardiomyopathy and greater than control (44.6 +/- 13.6 vs. 48.2 +/- 18.3 vs. 26.9 +/- 6.2; P < 0.05, and 34.6 +/- 13.4 vs. 30.8 +/- 10.9 vs. 16.7 +/- 3.7, respectively; P < 0.05). ACTEF was lower in idiopathic than in ischemic cardiomyopathy and in the latter it was similar to control (18 +/- 10% vs. 32 +/- 10% vs. 36 +/- 10%, respectively; P < 0.05). Moreover, ACTEF was inversely related to left atrial tension at end-of atrial systole both in idiopathic and in ischemic cardiomyopathy (r2 = 0.52, P = 0.001 and r2 = 0.57, P = 0.0007, respectively). However, at any given level of left atrial tension at end of atrial systole, ACTEF was lower in idiopathic than ischemic cardiomyopathy. CONCLUSION: Left atrial systolic function is depressed in idiopathic and preserved in ischemic dilated cardiomyopathy despite similar left atrial loading conditions. This finding suggests left atrial myopathy in the former, and may be related to the differences in the response to medical treatment and clinical outcome observed between the two conditions.

Elevated plasma immunoreactive leptin levels preexist in healthy offspring of patients with essential hypertension.

BACKGROUND: Plasma leptin levels and plasma insulin levels have been found to be elevated in patients with essential hypertension (EH) and have been suggested to be components of the metabolic syndrome. Increased heart rate (HR) may predict the development of EH in normal or borderline-hypertensive individuals. The aim of our study was to test the hypothesis that elevated plasma leptin and insulin levels as well as systolic blood pressure (SBP) and diastolic blood pressure (DBP) and increased resting HR preexist in the healthy offspring of patients with EH. METHODS AND RESULTS: Twenty-six (12 male, 14 female) healthy offspring of hypertensive patients, mean age 16 +/- 2.5 years and body mass index (BMI) of 21.5 +/- 2.8 kg/m(2) (group A), and 30 (14 male, 16 female) healthy offspring of normotensive patients, mean age 17 +/- 2.3 years and BMI of 21.9 +/- 2.4 kg/m(2) (group B), were studied. (The two groups were matched for sex, age, and BMI). Mean SBP, DBP, resting HR, plasma leptin, and plasma insulin levels (radioimmunoassay method) were determined in the whole study population. Mean SBP, DBP, and resting HR were significantly higher in group A than in group B (120 +/- 12 vs 112 +/- 9.5 mm Hg, 77 +/- 9 vs 72 +/- 7 mm Hg, 79 +/- 8 vs 75 +/- 5 beats/min, P <.01, P <.05, and P <.05, respectively). Plasma leptin and insulin levels were significantly higher in group A than in group B (9 +/- 5.06 vs 5.6 +/- 2.5 ng/mL and 20.11 +/- 11.3 vs 14.8 +/- 5.2 microIU/mL, P <.01 and P <.05, respectively). CONCLUSIONS: Our findings support the hypothesis that hyperleptinemia, hyperinsulinemia, and elevated blood pressure and resting HR preexist in the healthy offspring of patients with EH.

Transcatheter closure of atrial septal defects in adults with the Amplatzer septal occluder.

OBJECTIVE: To assess the efficacy and complications of device occlusion of atrial septal defects in adults, using the Amplatzer septal occluder (ASO). DESIGN: A prospective interventional study. SETTING: Paediatric cardiology departments in two European teaching hospitals. PATIENTS: The first 20 patients accepted for atrial septal defect device occlusion, on the basis of transoesophageal echocardiography. Sixteen patients had larger defects with right heart dilatation, while the primary indication for closure in four was a history of early paradoxical embolism. INTERVENTIONS: Transcatheter atrial septal defect occlusions performed under transoesophageal echocardiography and fluoroscopic guidance between December 1996 and June 1998. OUTCOME MEASURES: Success of deployment of ASO devices, procedure and fluoroscopic times, complications, and symptoms. RESULTS: The ASO device was successfully implanted in all 20 patients (14 female), median age 44.2 years, with no complications. Of the 16 patients with right heart dilatation, the median Qp:Qs was 2.5:1. Defects measured 11-22 mm (median 18) on transoesophageal echocardiography, with balloon sized diameter (and device size) of 13-28 mm (median 20). For all 20 patients, the procedure time ranged from 38-78 minutes (median 61), and fluoroscopy 8.4-24.7 minutes (median 15.2). There were residual shunts in three patients at the end of the procedure, which were trivial (

Intermittent milrinone effect on long-term hemodynamic profile in patients with severe congestive heart failure.

BACKGROUND: Many reports have suggested that intermittent milrinone infusion (IMI) may be efficacious in the management of end-stage congestive heart failure (CHF), but this issue has not been clearly established. The aim of our study was to investigate the effectiveness of IMI in hospitalized patients with severe CHF undergoing long-term (4 months) post-therapy hemodynamics. METHODS: Thirty-six patients (28 men, 8 women; mean age 65.6 +/- 8.2 years old) with end-stage CHF (New York Heart Association functional class III-IV) were studied. Each patient received 4 cycles of 3 days per week with milrinone therapy. Each cycle consisted of a loading dose of 50 microgram/kg over 10 minutes and a 72-hour continuous infusion of 0.5 microgram/kg per minute under close monitoring. Hemodynamic changes were determined during the first and fourth cycles and on 4-month reexamination. Full clinical examination was performed at the beginning (baseline) and at the end of 4-month follow-up. RESULTS: The values of mean pulmonary arterial pressure, pulmonary capillary wedge pressure, systemic vascular resistance, and pulmonary vascular resistance were significantly decreased (P <.01) and cardiac index was significantly increased (P <.01) compared with the baseline of first and fourth cycles. At the end of the 4-month follow-up period all hemodynamic parameters sustained the improvement. Clinical examination at the end of the 4-month period showed that 21 (58.3%) of 36 patients remained in New York Heart Association functional class IV but were hemodynamically improved, 13 (36.2%) of 36 were in functional class III, and 2 (5.5%) of 36 were in class II-III. There were no deaths during the study period. CONCLUSIONS: Our findings suggest that IMI in hospitalized patients with severe CHF is hemodynamically efficacious. This beneficial hemodynamic effect is maintained for at least 4 months after discontinuation of therapy. These promising results raised the possibility that given appropriately, milrinone may have an important role in end-stage CHF.

Echocardiographic features of primary, secondary and familial amyloidosis.

BACKGROUND: Currently recognized types of amyloidosis include primary, familial and secondary, each of which may affect the heart. There may be differences in the heart response to the deposition of amyloid fibrils in these three forms of the disease. MATERIALS AND METHODS: Over a period of 10 years (1985-95), 28 consecutive patients with primary, 11 with secondary and 17 with familial amyloidosis were studied at the Departments of Cardiology of Laiko and Hammersmith Hospitals. The diagnosis of amyloidosis was confirmed by biopsies of subcutaneous fat, rectum, kidney, bone marrow, gum or sural nerve. Diagnosis of cardiac involvement was based on typical electrocardiographic and echocardiographic findings. RESULTS: The left ventricular fractional shortening (%) was reduced in primary compared with familial or secondary amyloidosis (29.8 +/- 10.2 vs. 36.2 +/- 6.5 vs. 36 +/- 5.9, P < 0.05). The transmitral flow velocity pattern was compatible with abnormal relaxation in most patients in the three groups [primary 16 (57%), familial 11 (64. 7%), secondary 6 (54.5%), P = NS]. Right ventricular systolic dysfunction (right ventricular dP/dt < 220 mmHg s-1 or tricuspid annulus systolic excursion < 10 mm) was present in 8 (28.6%), 2 (11. 8%) and 0 patients. Patients with primary amyloidosis were followed up for 15 +/- 6 months. There were 12 deaths, and repeat echocardiography in the survivors revealed a significant deterioration of left ventricular systolic function (fractional shortening = 23.6% +/- 8.8%, P < 0.05 vs. baseline). CONCLUSION: Primary amyloidosis is characterized by more severe cardiac involvement than the familial or secondary amyloidosis and has an ominous course.