or transthyretin (ATTR) 2-4 types in the vast majority of cases. ATTR amyloidosis may be acquired, associated with wild-type Background-Cardiac transthyretin (ATTR) amyloidosis is a progressive and fatal cardiomyopathy for which several promising therapies are in development. The diagnosis is frequently delayed or missed because of the limited specificity of echocardiography and the traditional requirement for histological confirmation. It has long been recognized that technetium-labeled bone scintigraphy tracers can localize to myocardial amyloid deposits, and use of this imaging modality for the diagnosis of cardiac ATTR amyloidosis has lately been revisited. We conducted a multicenter study to ascertain the diagnostic value of bone scintigraphy in this disease. Methods and Results-Results of bone scintigraphy and biochemical investigations were analyzed from 1217 patients with suspected cardiac amyloidosis referred for evaluation in specialist centers. Of 857 patients with histologically proven amyloid (374 with endomyocardial biopsies) and 360 patients subsequently confirmed to have nonamyloid cardiomyopathies, myocardial radiotracer uptake on bone scintigraphy was >99% sensitive and 86% specific for cardiac ATTR amyloid, with false positives almost exclusively from uptake in patients with cardiac AL amyloidosis. Importantly, the combined findings of grade 2 or 3 myocardial radiotracer uptake on bone scintigraphy and the absence of a monoclonal protein in serum or urine had a specificity and positive predictive value for cardiac ATTR amyloidosis of 100% (positive predictive value confidence interval, 98.0-100). Conclusions-Bone scintigraphy enables the diagnosis of cardiac ATTR amyloidosis to be made reliably without the need for histology in patients who do not have a monoclonal gammopathy. We propose noninvasive diagnostic criteria for cardiac ATTR amyloidosis that are applicable to the majority of patients with this disease. Clinical Perspective on p 2412Autopsy studies have shown the presence of cardiac ATTR amyloid deposits in up to 25% of individuals >80 years of age, although in many of these hearts the amount of amyloid was small.8 Nevertheless, among patients with heart failure and preserved ejection fraction, postmortem examination indicates that cardiac amyloid deposition is commoner than in an age-matched autopsy group without heart failure. The majority of patients with cardiac amyloid on postmortem in these studies had not had amyloidosis diagnosed during their lifetime.9 Echocardiography, although a valuable and widely accessible tool for investigating heart failure, is neither sensitive nor specific for cardiac amyloidosis.10 Typical findings on echocardiography include thickening of ventricular walls, restrictive filling, abnormal left and right ventricular longitudinal strain, and atrial septal thickening.11 Cardiac magnetic resonance imaging (CMR) has much greater diagnostic value in cardiac amyloidosis, but false-positive and false-negative CMRs are not infrequent.12 Typical findings ...
This simple, universally applicable staging system stratifies patients with both ATTRwt and ATTRv amyloid cardiomyopathy into prognostic categories. It will be of value in the design of forthcoming clinical trials of novel amyloid-specific therapies.
Background: Transthyretin amyloidosis cardiomyopathy (ATTR-CM) is an increasingly recognized cause of heart failure in older individuals. We sought to characterize the natural history of ATTR-CM and compare outcomes and quality of life among patients with acquired and hereditary forms of the disease. Methods: We studied 711 patients with wild-type ATTR-CM, 205 with hereditary ATTR-CM associated with the V122I variant (V122I-hATTR-CM), and 118 with non-V122I-hATTR-CM at the UK National Amyloidosis Center between 2000 and 2017. Patients underwent prospective protocolized evaluations comprising assessment of cardiac parameters, functional status by 6-minute walk test, quality of life according to the Kansas City Cardiomyopathy Questionnaire, and survival. Hospital service usage pre- and postdiagnosis was established using English central health records in a subset of patients. Results: There was substantial diagnostic delay, with patients using hospital services a median (interquartile range) of 17 (9–27) times during the 3 years before diagnosis, by which time quality of life was poor; diagnosis of wild-type ATTR-CM was delayed >4 years after presentation with cardiac symptoms in 42% of cases. Patients with V122I-hATTR-CM were more impaired functionally ( P <0.001) and had worse measures of cardiac disease ( P <0.001) at the time of diagnosis, a greater decline in quality of life, and poorer survival ( P <0.001) in comparison with the other subgroups. Conclusions: ATTR-CM is an inexorably progressive and eventually fatal cardiomyopathy associated with poor quality of life. Diagnosis is often delayed for many years after symptoms develop. Improved awareness and wider use of recently validated diagnostic imaging methods are urgently required for patients to benefit from recent therapeutic developments.
Disclosures:Professor Moon has received an unrestricted research grant from GSK. He has also been paid a consultancy fee for trial design.
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