Objectives This study sought to explore the potential role of noncontrast myocardial T1 mapping for detection of cardiac involvement in patients with primary amyloid light-chain (AL) amyloidosis. ...Background Cardiac involvement carries a poor prognosis in systemic AL amyloidosis. Late gadolinium enhancement (LGE) cardiac magnetic resonance (CMR) is useful for the detection of cardiac amyloid, but characteristic LGE patterns do not always occur or they appear late in the disease. Noncontrast characterization of amyloidotic myocardium with T1 mapping may improve disease detection. Furthermore, quantitative assessment of myocardial amyloid load would be of great value. Methods Fifty-three AL amyloidosis patients (14 with no cardiac involvement, 11 with possible involvement, and 28 with definite cardiac involvement based on standard biomarker and echocardiographic criteria) underwent CMR (1.5-T) including noncontrast T1 mapping (shortened modified look-locker inversion recovery ShMOLLI sequence) and LGE imaging. These were compared with 36 healthy volunteers and 17 patients with aortic stenosis and a comparable degree of left ventricular hypertrophy as the cardiac amyloid patients. Results Myocardial T1 was significantly elevated in cardiac AL amyloidosis patients (1,140 ± 61 ms) compared to normal subjects (958 ± 20 ms, p < 0.001) and patients with aortic stenosis (979 ± 51 ms, p < 0.001). Myocardial T1 was increased in AL amyloid even when cardiac involvement was uncertain (1,048 ± 48 ms) or thought absent (1,009 ± 31 ms). A noncontrast myocardial T1 cutoff of 1,020 ms yielded 92% accuracy for identifying amyloid patients with possible or definite cardiac involvement. In the AL amyloidosis cohort, there were significant correlations between myocardial T1 time and indices of systolic and diastolic dysfunction. Conclusions Noncontrast T1 mapping has high diagnostic accuracy for detecting cardiac AL amyloidosis, correlates well with markers of systolic and diastolic dysfunction, and is potentially more sensitive for detecting early disease than LGE imaging. Elevated myocardial T1 may represent a direct marker of cardiac amyloid load. Further studies are needed to assess the prognostic significance of T1 elevation.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPUK, ZAGLJ, ZRSKP
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Native T1 Mapping in Transthyretin Amyloidosis Fontana, Marianna, MD; Banypersad, Sanjay M., MB ChB; Treibel, Thomas A., MBBS ...
JACC. Cardiovascular imaging,
02/2014, Volume:
7, Issue:
2
Journal Article
Peer reviewed
Open access
Objectives The aims of the study were to explore the ability of native myocardial T1 mapping by cardiac magnetic resonance to: 1) detect cardiac involvement in patients with transthyretin amyloidosis ...(ATTR amyloidosis); 2) track the cardiac amyloid burden; and 3) detect early disease. Background ATTR amyloidosis is an underdiagnosed cause of heart failure, with no truly quantitative test. In cardiac immunoglobulin light-chain amyloidosis (AL amyloidosis), T1 has high diagnostic accuracy and tracks disease. Here, the diagnostic role of native T1 mapping in the other key type of cardiac amyloid, ATTR amyloidosis, is assessed. Methods A total of 3 groups were studied: ATTR amyloid patients (n = 85; 70 males, age 73 ± 10 years); healthy individuals with transthyretin mutations in whom standard cardiac investigations were normal (n = 8; 3 males, age 47 ± 6 years); and AL amyloid patients (n = 79; 55 males, age 62 ± 10 years). These were compared with 52 healthy volunteers and 46 patients with hypertrophic cardiomyopathy (HCM). All underwent T1 mapping (shortened modified look-locker inversion recovery); ATTR patients and mutation carriers also underwent cardiac 3,3-diphosphono-1,2-propanodicarboxylicacid (DPD) scintigraphy. Results T1 was elevated in ATTR patients compared with HCM and normal subjects (1,097 ± 43 ms vs. 1,026 ± 64 ms vs. 967 ± 34 ms, respectively; both p < 0.0001). In established cardiac ATTR amyloidosis, T1 elevation was not as high as in AL amyloidosis (AL 1,130 ± 68 ms; p = 0.01). Diagnostic performance was similar for AL and ATTR amyloid (vs. HCM: AL area under the curve 0.84 95% confidence interval: 0.76 to 0.92; ATTR area under the curve 0.85 95% confidence interval: 0.77 to 0.92; p < 0.0001). T1 tracked cardiac amyloid burden as determined semiquantitatively by DPD scintigraphy (p < 0.0001). T1 was not elevated in mutation carriers (952 ± 35 ms) but was in isolated DPD grade 1 (n = 9, 1,037 ± 60 ms; p = 0.001). Conclusions Native myocardial T1 mapping detects cardiac ATTR amyloid with similar diagnostic performance and disease tracking to AL amyloid, but with lower maximal T1 elevation, and appears to be an early disease marker.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPUK, ZAGLJ, ZRSKP
Objectives This study was devised to describe the different cardiac magnetic resonance (CMR) appearances in light chain amyloid (AL) and transthyretin-related amyloidosis (ATTR). Background CMR is ...increasingly used to investigate patients with suspected amyloidosis. Global subendocardial late gadolinium enhancement (LGE) has been reported as typical of AL amyloidosis, whereas different patterns have been noted in ATTR amyloidosis. Methods We performed de novo analyses on original DICOM magnetic resonance imaging in 46 patients with cardiac AL amyloidosis and 51 patients with ATTR type who had been referred to a specialist amyloidosis center between 2007 and 2012 after CMR. Histological examination was performed in all cases, with immunohistochemistry, to confirm systemic amyloidosis. Results Patients' median age was 68 ± 10 years, and 74% were male. Left ventricular mass was markedly increased in ATTR amyloidosis (228 g 202 to 267 g) compared with AL type (167 g 137 to 191 g) (p < 0.001). LGE was detected in all but 1 cardiac amyloidosis patient (AL type) and was substantially more extensive in ATTR compared with AL amyloidosis. Ninety percent of ATTR patients demonstrated transmural LGE compared with 37% of AL patients (p < 0.001). Right ventricular LGE was apparent in all ATTR patients but in only 33 AL patients (72%) (p < 0.001). Despite these findings, survival was significantly better in cardiac ATTR amyloidosis compared with AL type. We derived an LGE scoring system (Query Amyloid Late Enhancement) that independently differentiated ATTR from AL amyloidosis and, when incorporated into a logistic regression model with age and wall thickness, detected ATTR type with 87% sensitivity and 96% specificity. Conclusions Transmural patterns of LGE distinguished ATTR from AL cardiac amyloidosis with high accuracy in this real-world analysis of CMR. Precise diagnosis of cardiac amyloidosis is crucial given the role of chemotherapy in AL type and with novel therapies for ATTR type currently in development.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPUK, ZAGLJ, ZRSKP
Evaluation and Management of the Cardiac Amyloidosis Selvanayagam, Joseph B., FRACP, DPhil; Hawkins, Philip N., PhD, FRCP, FRCPath; Paul, Biju, MBBS ...
Journal of the American College of Cardiology,
11/2007, Volume:
50, Issue:
22
Journal Article
Peer reviewed
Open access
Evaluation and Management of the Cardiac Amyloidosis Joseph B. Selvanayagam, Philip N. Hawkins, Biju Paul, Saul G. Myerson, Stefan Neubauer This review summarizes the current state of evidence for ...the evaluation and management of cardiac amyloidosis. The electrocardiographic and echocardiographic features that are the best discriminators for disease are discussed and the evidence for this is critically appraised. The recent evidence from cardiovascular magnetic resonance imaging and prognostic implications of elevated biochemical markers are summarized. Intermediate-dose infusional chemotherapy regimes and high-dose chemotherapy with peripheral stem cell rescue remain the mainstay of disease treatment. Future strategies to stabilize the native structures of amyloidogenic proteins, to disrupt established deposits using antibodies, and small-molecule drugs are discussed.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPUK, ZAGLJ, ZRSKP
Background About 4% of African Americans possess the isoleucine 122 (V122I) variant of transthyretin, associated with cardiac amyloidosis beyond ages of 55 to 60 years. Transthyretin amyloidosis ...associated with variant V122I (ATTR V122I) is likely to be an important cause of heart failure in Afro-Caribbean populations, but the high prevalence of left ventricular hypertrophy (LVH) and lack of awareness of this genetic disorder pose diagnostic hurdles. We report the electrocardiographic (ECG) features of ATTR V122I in the largest clinical series to date. Methods Patients with ATTR V122I were identified in collaboration with the UK National Amyloidosis Centre. The ECG at presentation was assessed for cardiac rhythm, axis, and voltage complex size. Results We include 64 patients with ATTR V122I, with a median age of 74 years (range, 57-88 years). Normal or increased ECG voltage was present in 44.3% of patients, and overall 25% met the criteria for LVH. A significant negative correlation between voltage complex size and duration of illness was seen ( P < .05). First-degree heart block was evident in 56% of patients in sinus rhythm. During follow-up (n = 17; median, 28 months), 50% of patients with initial first-degree heart block required pacing. Conclusion Electrocardiographic voltages meet the criteria for LVH in one quarter of patients with ATTR V122I cardiac amyloidosis. The widely held belief that cardiac amyloidosis is associated with low-voltage complexes is likely to contribute to underdiagnosis of ATTR V122I. First-degree heart block is common at diagnosis and identifies patients at high risk for subsequent pacing requirement.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Summary Idiopathic recurrent pericarditis (IRP) impairs quality of life. Although its precise etiology is not certain, it is believed to be immunologically mediated. Its optimal treatments are ...unknown. Initial therapy is with non-steroidal anti-inflammatory drugs and colchicine. Steroids, which are often used, however may promote recurrences. European guidelines advocate azathioprine or cyclophosphamide in refractory cases despite limited evidence. We report two adults with IRP successfully treated with the interleukin-1 antagonist, anakinra. We combine this experience with the first systematic literature review of immunosuppression in IRP. A total of 8 papers were included in the review, which alongside our patients described 18 cases. The best treatments comprised anakinra and intravenous immunoglobulin, with respective remission rates of 100% and 67%. Cyclophosphamide and azathioprine were less efficacious. The unprovoked inflammatory episodes in our patients alongside their prompt response to anakinra indicate that in some instances IRP may represent an autoinflammatory condition. We suggest that in IRP refractory to initial treatment, anakinra should be considered as a potential therapy. Clinical trials are required to confirm its benefits in IRP.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPUK, ZAGLJ, ZRSKP
Objectives The aim of this study was to determine the accuracy of the contrast “bolus only” T1 mapping cardiac magnetic resonance (CMR) technique for measuring myocardial extracellular volume ...fraction (ECV). Background Myocardial ECV can be measured with T1 mapping before and after contrast agent if the contrast agent distribution between blood/myocardium is at equilibrium. Equilibrium distribution can be achieved with a primed contrast infusion (equilibrium contrast-CMR EQ-CMR) or might be approximated by the dynamic equilibration achieved by delayed post-bolus measurement. This bolus only approach is highly attractive, but currently limited data support its use. We compared the bolus only technique with 2 independent standards: collagen volume fraction (CVF) from myocardial biopsy in aortic stenosis (AS); and the infusion technique in 5 representative conditions. Methods One hundred forty-seven subjects were studied: healthy volunteers (n = 50); hypertrophic cardiomyopathy (n = 25); severe AS (n = 22); amyloid (n = 20); and chronic myocardial infarction (n = 30). Bolus only (at 15 min) and infusion ECV measurements were performed and compared. In 18 subjects with severe AS the results were compared with histological CVF. Results The ECV by both techniques correlated with histological CVF (n = 18, r2 = 0.69, p < 0.01 vs. r2 = 0.71, p < 0.01, p = 0.42 for comparison). Across health and disease, there was strong correlation between the techniques (r2 = 0.97). However, in diseases of high ECV (amyloid, hypertrophic cardiomyopathy late gadolinium enhancement, and infarction), Bland-Altman analysis indicates the bolus only technique has a consistent and increasing offset, giving a higher value for ECVs above 0.4 (mean difference ± limit of agreement for ECV <0.4 = −0.004 ± 0.037 vs. ECV >0.4 = 0.040 ± 0.075, p < 0.001). Conclusions Bolus only, T1 mapping-derived ECV measurement is sufficient for ECV measurement across a range of cardiac diseases, and this approach is histologically validated in AS. However, when ECV is >0.4, the bolus only technique consistently measures ECV higher compared with infusion.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPUK, ZAGLJ, ZRSKP
Reply Selvanayagam, Joseph B., MBBS (Hons), FRACP, DPhil, FESC; Hawkins, Philip N., PhD, FRCP, FRCPath; Neubauer, Stefan, MD, FRCP
Journal of the American College of Cardiology,
2008, Volume:
51, Issue:
15
Journal Article
Peer reviewed
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPUK, ZAGLJ, ZRSKP
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