| Cardiac amyloidosis (CA) is a myocardial disease characterized by extracellular amyloid infiltration throughout the heart. Amyloid deposits occur in the ventricles and atria, as well as vessels and valves. The conduction system may also be involved. The clinical manifestation of CA is multiple. The early diagnosis of CA is difficult and it is easy to be misdiagnosed for other diseases.Objective1. To investigate the clinical features in patients with CA.2. To evaluate the value of endomyocardial biopsy (EMB) for the diagnosis of CA.Methods1. The findings of clinical manifestation, laboratory, electrocardiogram, echocardiogram, CMR,18F-FDG PET/CT and99Tcm-MDP scintigraphy in patients with CA admitted to Peking Union Medical College Hospital from January,2000to January2012were retrospectively studied. The sensitivity of biopsy of different organs and tissues for diagnosing systemic amyloidosis were analysed. The control group was consisted of subjects with systemic amyloidosis without CA.2. Patients who were suspected to have CA underwent EMB and were evaluated by Congo Red stained and by ultrastructural study with electron microscopy.3. The genes for transthyretin (TTR) and apolipoprotein A-I (Apo-A-I) were studied in14patients with EMB verified CA.Results1. Of the343patients diagnosed with amyloidosis,289had evidence of systemic amyloidosis and were enrolled in this analysis. The median duration from initially reffering to doctors to the final diagnosis was7months (0-360months) in patients with systemic amyloidosis.54patients (18.7%) were misdiagnosed during the course of the disease.33patients (11.4%) died during their in-hospital stay or discharged for poor condition.194patients (67.1%) with CA had a significantly higher incidence of edema of lower extremity (70.6%vs48.4%, P<0.001), dyspnea (65.5%vs29.5%, P<0.001), pleural effusions (50.0%vs13.7%, P<0.001), hypotension (14.9%vs3.2%, P=0.003), syncope (8.8%vs0,P=0.003), thrombus (7.2%vs1.1%, P=0.025)than the control.2. The incidence of atrial fibrillation (12.2%vs3.4%, P=0.021), conduction abnormalities (20.6%vs3.4%, P<0.001), low limb lead voltage (54.2%vs20.9%, P<0.001), patterns similar to old myocardial infarction (40.2%vs4.6%, P<0.001) were significantly higher in the patients with CA than the control. Echocardiogram showed left ventricular hypertrophy, left ventricular diastolic dysfunction, granular appearance of the myocardium. Patients with CA were also likely to have left atrial enlargement, pericardial effusion and left ventricular systolic dysfunction. Left ventricular global subendocardial delayed gadolinium enhancement or transmural delayed gadolinium enhancement were found in11patients with CA.3patients with CA underwent18F-FDG PET/CT scan, and a lesion with intense18F-FDG activity in the heart was demonstrated in1patient. Extensive soft tissue uptake of99Tcm-MDP was showed in33patients (28.0%) with systemic amyloidosis, and27patients (81.8%) of them belonged to CA group.3. The sensitivity of biopsy of heart (90.5%, n=21), kidney (86.5%, n=37) and tone (90.9%, n=11) for diagnosing amyloidosis were high in patients with C A, but the sensitivity of biopsy of gingiva (51.2%, n=41), subcutaneous abdominal fat (38.6%, n=57), rectum (16.7%, n=24) and bone marrow (7.5%, n=94) were low. The sensitivity (58.3%, n=36) would increase when the biopsy of subcutaneous abdominal fat and soft tissues in oral cavity were combined in patients with CA.4.24patients who had clinical, laboratory and echocardiographic evidence of amyloidosis underwent EMB. Amyloid was found in21patients (87.5%) with a positive result of EMB or noncardiac biopsy. EMB specimens stained positively with Congo red in19patients (19/21,90.5%), and14(14/19,73.7%) showed a Congo red negative result of noncardiac biopsy. EMB specimens from3patients (Congo red negative) were evaluated with electron microscopy, the diagnosis was made by ultrastructural identification of amyloid fibrils in2patients. Electron microscopy showed amyloid located in myocardial interstitium as well as in the wall of small vessels. The cell membrane remained in some areas but in other areas it had disappeared and was replaced by masses of amyloid which formed a thick mass around the cell. Large numbers of mitochondria were recognizable in the myocardial cells with the myofibrils well preserved, but there seemed to be a reduction in the number of mitochondria in the muscle cells which were reduced in size. The mitochondria were swollen and their cristae fragmented. Cardiac fibroblasts were activated and the extracellular matrix remodeling in the myocardium tissue was observed.5. Of the14patients with EMB verified CA performed genetic analysis, the diagnosis of7patients was AL amyloidosis and the exact type of the remaining7patients were not determined. Amyloidogenic mutations were present in1of the14patients (7.1%) with EMB verified CA (TTR, c.149T>C, Val30Ala). Conclusions1. The clinical manifestation of systemic amyloidosis is multiple, and it is easy to be misdiagnosed for other diseases. The in-hospital mortality of systemic amyloidosis is high. Heart is one ofthe organs most commonly involved. Review of the echocardiogram in conjunction with the ECG is helpful in making a correct diagnosis. CMR is another noninvasive diagnostic method of CA.The sensitivity ofbiopsyofheart, kidney and tone for diagnosing amyloidosis are high in patients with CA, but the sensitivity of biopsy of gingiva, subcutaneous abdominal fat are low. The sensitivity would increase when the biopsy of subcutaneous abdominal fat and soft tissues in oral cavity are combined in patients with CA.2. EMB is valuable in the diagnosis of CA. EMB is a safe and relatively simple procedure if the diagnosis is not confirmed by biopsy of another tissue in patients with suspected CA. Ultrastructural identification of amyloid fibrils with electron microscopy is a method of choice for patients with highly suspected CA who showed a Congo red negative result of EMB specimens.3. Genetic analysis is valuable in determining the types of CA. |
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