| 1. |
- Antoni, Gunnar, et al.
(författare)
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In Vivo Visualization of Amyloid Deposits in the Heart with C-11-PIB and PET
- 2013
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Ingår i: Journal of Nuclear Medicine. - : Society of Nuclear Medicine. - 0161-5505 .- 1535-5667 .- 2159-662X. ; 54:2, s. 213-220
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Tidskriftsartikel (refereegranskat)abstract
- Cardiac amyloidosis is a differential diagnosis in heart failure and is associated with high mortality. There is currently no noninvasive imaging test available for specific diagnosis. N-[methyl-C-11]2-(4'-methylamino-phenyl)-6-hydroxybenzothiazole (C-11-PIB) PET is used in the evaluation of brain amyloidosis. We evaluated the potential use of C-11-PIB PET in systemic amyloidosis affecting the heart. Methods: Patients (n = 10) diagnosed with systemic amyloidosis-including heart involvement of either monoclonal immunoglobulin light-chain (AL) or transthyretin (ATTR) type- and healthy volunteers (n = 5) were investigated with PET/CT using C-11-PIB to study cardiac amyloid deposits and with C-11-acetate to measure myocardial blood flow to study the impact of global and regional perfusion on PIB retention. Results: Myocardial C-11-PIB uptake was visually evident in all patients 15-25 min after injection and was not seen in any volunteer. A significant difference in C-11-PIB retention in the heart between patients and healthy controls was found. The data indicate that myocardial amyloid deposits in patients diagnosed with systemic amyloidosis could be visualized with C-11-PIB. No correlation between C-11-PIB retention index and myocardial blood flow as measured with C-11-acetate was found on the global level, whereas a positive correlation on the segmental level was seen in a single patient. Conclusion: C-11-PIB and PET could be a method to study systemic amyloidosis of type AL and ATTR affecting the heart and should be investigated further both as a diagnostic tool and as a noninvasive method for treatment follow-up.
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| 2. |
- Granstam, Sven-Olof, et al.
(författare)
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Evaluation of patients with cardiac amyloidosis using echocardiography, ECG and right heart catheterization
- 2013
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Ingår i: Amyloid. - : Informa UK Limited. - 1350-6129 .- 1744-2818. ; 20:1, s. 27-33
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Tidskriftsartikel (refereegranskat)abstract
- Aims:To characterize patients with cardiac amyloidosis using echocardiography, electrocardiogram (ECG) and right heart catheterization (RHC).Methods and results:Fourteen patients with biopsy verified light chain or transthyretin cardiac amyloidosis were included. All patients had heart failure with markedly elevated NT-proBNP. Echocardiography demonstrated biventricular hypertrophy, left atrial enlargement and normal to slightly reduced left ventricular ejection fraction. Tissue Doppler septal e´ was low and median E/e´ was high. Within 6 months RHC was performed in eight of the patients. The restrictive filling pattern demonstrated by echocardiography corresponded well to median pulmonary wedge pressure (21 mmHg). Systolic pulmonary artery pressure (SPAP) was increased, whereas cardiac output and stroke volume were seen to be decreased with both methods. ECG demonstrated: low voltage (36%), abnormal R-progression (65%), ST-T abnormalities (71%) and high incidence of fibrillation (36%). In addition, a case report following the treatment of melphalan and dexamethasone is presented with improvement of hypertrophy, SPAP, left ventricular mass and e´.Conclusion: These findings should lead to a suspicion of cardiac amyloidosis and suggest further investigation.
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| 3. |
- Kero, Tanja, et al.
(författare)
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Quantification of (11)C-PIB kinetics in cardiac amyloidosis
- 2020
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Ingår i: Journal of Nuclear Cardiology. - : Springer Science and Business Media LLC. - 1071-3581 .- 1532-6551. ; 27:3, s. 774-784
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The purpose of this work was to determine the optimal tracer kinetic model of (11)C-PIB and to validate the use of the simplified methods retention index (RI) and standardized uptake value (SUV) for quantification of cardiac (11)C-PIB uptake in amyloidosis. METHODS AND RESULTS: Single-tissue, reversible and irreversible two-tissue models were fitted to data from seven cardiac amyloidosis patients who underwent (11)C-PIB PET scans and arterial blood sampling for measurement of blood radioactivity and metabolites. The irreversible two-tissue model (2Tirr) best described cardiac (11)C-PIB uptake. RI and SUV showed high correlation with the rate of irreversible binding (Ki) from the 2Tirr model (r(2 )=0.95 and r(2 )=0.94). Retrospective data from 10 amyloidosis patients and 5 healthy controls were analyzed using RI, SUV, as well as compartment modelling with a population-average metabolite correction. All measures were higher in amyloidosis patients than in healthy controls (p=.001), but with an overlap between groups for Ki. CONCLUSION: An irreversible two-tissue model best describes the (11)C-PIB uptake in cardiac amyloidosis. RI and SUV correlate well with Ki from the 2Tirr model. RI and SUV discriminate better between amyloidosis patients and controls than Ki based on population-average metabolite correction.
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| 4. |
- Rosengren, Sara, 1978-
(författare)
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AL amyloidosis : Study of epidemiology, diagnosis and treatment with emphasis on heart involvement
- 2024
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- AL (immunoglobulin light chain) amyloidosis is often associated with delayed diagnosis and thereby high early mortality that is not overcome by contemporary treatment. There is a need for diagnostic methods promoting earlier diagnosis, especially in patients with cardiac involvement. Progress has been made in the treatment of AL amyloidosis and prolonged survival has been reported from specialized referral centers. However, population-based reports are scarce regarding epidemiology as well as treatment outcomes. Aims of this thesis were to increase the knowledge of the epidemiology of AL amyloidosis, investigate new imaging methods for early diagnosis and prognostication in cardiac amyloidosis (CA), and evaluate treatment options with focus on patients with cardiac involvement. In paper I we presented real-world long-term results of treatment with high dose chemotherapy for AL amyloidosis in Sweden. We could conclude that long overall survival (median 8.2 years, 95% CI 5.1-11.2) was reached with high dose chemotherapy, but with inferior outcomes in patients with cardiac involvement. Treatment related mortality was comparable to that reported from larger centers during this period and was decreasing from 23.8% to 7.8% during the studied time period.In paper II we studied the accuracy of PET with the amyloid binding tracer 11C-PIB for the diagnosis of CA. 11C-PIB PET showed high accuracy in detecting CA, and affinity was higher for AL compared to transthyretin amyloidosis. We concluded that 11C-PIB PET can be a useful method to rule in or out amyloidosis in patients with unexplained diastolic heart failure. Our results also indicated that 11C-PIB PET can detect CA at an earlier stage than echocardiography and might be a useful tool for early diagnosis.In paper III we studied the prognostic value of cardiac function parameters from 11C-acetate PET in CA. We found that reduced myocardial external efficiency was associated with inferior survival in CA patients. However, the strongest prognostic parameter was lowered ratio of forward stroke volume and left ventricular mass, which was the only independently prognostic parameter in multivariable analysis. Paper IV was a population-based epidemiological study in which we could determine the standardized incidence of systemic AL amyloidosis to 12.0 (95% CI 9.3-14.7) per million person-years for Uppsala County, without significant change during the period 2000-2020. The 5-year limited duration prevalence increased numerically, but without statistical significance. Prolonged overall survival was observed over time, and there was also a decrease in early mortality, indicating earlier diagnosis of especially patients with cardiac involvement.
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| 5. |
- Rosengren, Sara, et al.
(författare)
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Diagnostic Accuracy of [11C]PIB Positron Emission Tomography for Detection of Cardiac Amyloidosis
- 2020
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Ingår i: JACC Cardiovascular Imaging. - : Elsevier BV. - 1936-878X .- 1876-7591. ; 13:6, s. 1337-1347
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: This dual-site study evaluated the diagnostic accuracy of the method.BACKGROUND: Pittsburgh compound ([11C]PIB) positron emission tomography (PIB-PET) has shown promise as a specific and noninvasive method for the diagnosis of cardiac amyloidosis (CA).METHODS: The study had 2 parts. In the initial study, 51 subjects were included, 36 patients with known CA and increased wall thickness (15 immunoglobulin light chain [AL] and 21 transthyretin [ATTR] amyloidosis) and 15 control patients (7 were nonamyloid hypertrophic and 8 healthy volunteers). Subjects underwent PIB-PET and echocardiography. Sensitivity and specificity of PIB-PET were established for 2 simple semiquantitative approaches, standardized uptake value ratio (SUVR) and retention index (RI). The second part of the study included 11 amyloidosis patients (5 AL and 6 hereditary ATTR) without increased wall thickness to which the optimal cutoff values of SUVR (>1.09) and RI (>0.037 min-1) were applied prospectively.RESULTS: The diagnostic accuracy of visual inspection of [11C]PIB uptake was 100% in discriminating CA patients with increased wall thickness from controls. Semiquantitative [11C]PIB uptake discriminated CA from controls with a 94% (95% confidence interval [CI]: 80% to 99%) sensitivity for both SUVR and RI and specificity of 93% (95% CI: 66% to 100%) for SUVR and 100% (95% CI: 75% to 100%) for RI. [11C]PIB uptake was significantly higher in AL-CA than in ATTR-CA patients (p < 0.001) and discriminated AL-CA from controls with 100% (95% CI: 88% to 100%) accuracy for both the semiquantitative measures. In the prospective group without increased wall thickness, RI was elevated compared to controls (p = 0.001) and 5 of 11 subjects were evaluated as [11C]PIB PET positive.CONCLUSIONS: In a dual-center setting, [11C]PIB PET was highly accurate in detecting cardiac involvement in the main amyloid subtypes, with 100% accuracy in AL amyloidosis. A proportion of amyloidosis patients without known cardiac involvement were [11C]PIB PET positive, indicating that the method may detect early stages of CA.
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| 6. |
- Rosengren, Sara, et al.
(författare)
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Outcome of AL amyloidosis after high-dose melphalan and autologous stem cell transplantation in Sweden, long-term results from all patients treated in 1994-2009.
- 2016
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Ingår i: Bone Marrow Transplantation. - : Springer Science and Business Media LLC. - 0268-3369 .- 1476-5365. ; 51:12, s. 1569-1572
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Tidskriftsartikel (refereegranskat)abstract
- High-dose melphalan and autologous stem cell transplantation (HDM/ASCT) is widely used in immunoglobulin light chain (AL) amyloidosis, but the benefit is debated mainly because of the high treatment-related mortality (24% in a randomised study comparing HDM/ASCT with oral melphalan/dexamethasone). We report here on the long-term outcome of all patients treated with HDM/ASCT for AL amyloidosis in Sweden between 1994 and 2009. Seventy-two patients were treated at eight Swedish centres. Median follow-up was 67.5 months. At least partial response (organ or haematological) was seen in 64% of the patients. Median overall survival was 98 months or 8.2 years, with 5-year survival 63.9% and 10-year survival 43.4%. In patients with cardiac involvement or multiple organ involvement, survival was significantly shorter, median overall survival 49 and 56 months, respectively. All mortality within 100 days from ASCT was 12.5% for all patients and 17.2% in the patients with cardiac involvement. For patients treated in the earlier time period (1994-2001), 100-day mortality was 23.8% compared with 7.8% in the later period (2002-2009). In conclusion, long survival times can be achieved in patients with AL amyloidosis treated with HDM/ASCT, also in smaller centres. Early mortality is high, but with a decreasing trend over time.
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