| 1. |
- Anan, Intissar, et al.
(författare)
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Amyloid fibril composition type is consistent over time in patients with Val30Met (p. Val50Met) transthyretin amyloidosis
- 2022
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Ingår i: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 17:3
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Tidskriftsartikel (refereegranskat)abstract
- Background: We have previously shown that transthyretin (TTR) amyloidosis patients have amyloid fibrils of either of two compositions; type A fibrils consisting of large amounts of C-terminal TTR fragments in addition to full-length TTR, or type B fibrils consisting of only full-length TTR. Since type A fibrils are associated with an older age in ATTRVal30Met (p.Val50Met) amyloidosis patients, it has been discussed if the TTR fragments are derived from degradation of the amyloid deposits as the patients are aging. The present study aimed to investigate if the fibril composition type changes over time, especially if type B fibrils can shift to type A fibrils as the disease progresses.Material and methods: Abdominal adipose tissue biopsies from 29 Swedish ATTRVal30Met amyloidosis patients were investigated. The fibril type in the patients initial biopsy taken for diagnostic purposes was compared to a biopsy taken several years later (ranging between 2 and 13 years). The fibril composition type was determined by western blot.Results: All 29 patients had the same fibril composition type in both the initial and the follow-up biopsy (8 type A and 21 type B). Even patients with a disease duration of more than 12 years and an age over 75 years at the time of the follow-up biopsy had type B fibrils in both biopsies.Discussion: The result clearly shows that the amyloid fibril composition containing large amounts of C-terminal fragments (fibril type A) is a consequence of other factors than a slow degradation process occurring over time.
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| 2. |
- Arnberg, Elsa, et al.
(författare)
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RWT/SaVR-A Simple and Highly Accurate Measure Screening for Transthyretin Cardiac Amyloidosis
- 2022
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Ingår i: Journal of Clinical Medicine. - : MDPI. - 2077-0383. ; 11:14
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Cardiac amyloidosis is an underdiagnosed condition and simple methods for accurate diagnosis are warranted. We aimed to validate a novel, dual-modality approach to identify transthyretin cardiac amyloidosis (ATTR-CA), employing echocardiographic relative wall thickness (RWT), and ECG S-wave from aVR (SaVR), and compare its accuracy with conventional echocardiographic approaches.MATERIAL AND METHODS: We investigated 102 patients with ATTR-CA and 65 patients with left ventricular hypertrophy (LVH), all with septal thickness > 14 mm. We validated the accuracy of echocardiographic measures, including RWT, RWT/SaVR, posterior wall thickness (PWT), LV mass index (LVMI), left atrial volume index (LAVI), global longitudinal strain (GLS), and relative apical sparing (RELAPS) to identify ATTR-CA diagnosed using DPD-scintigraphy or abdominal fat biopsy.RESULTS: PWT, RWT, RELAPS, troponin, and RWT/SaVR were significantly higher in ATTR-CA compared to LVH. RWT/SaVR > 0.7 was the most accurate parameter to identify ATTR-CA (sensitivity 97%, specificity 90% and accuracy 91%). RELAPS was found to have much less accuracy (sensitivity 74%, specificity 76% and accuracy 73%).CONCLUSION: We can confirm the very strong diagnostic accuracy of RWT/SaVR to identify ATTR-CA in patients with septal thickness > 14 mm. Given its high sensitivity and specificity, RWT/SaVR > 0.7 has the potential to implement as a non-invasive, simple, and widely available diagnostic tool when screening for ATTR-CA.
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| 3. |
- Arvidsson, Sandra, 1986-, et al.
(författare)
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Amyloid Cardiomyopathy in Hereditary Transthyretin V30M Amyloidosis - Impact of Sex and Amyloid Fibril Composition
- 2015
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 10:11
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: Transthyretin V30M (ATTR V30M) amyloidosis is a phenotypically diverse disease with symptoms ranging from predominant neuropathy to exclusive cardiac manifestations. The aims of this study were to determine the dispersion of the two types of fibrils found in Swedish ATTR V30M patients -Type A consisting of a mixture of truncated and full length ATTR fibrils and type B fibrils consisting of full length fibrils, and to estimate the severity of cardiac dysfunction in relation to fibril composition and sex.MATERIAL AND METHODS: Echocardiographic data were analysed in 107 Swedish ATTR V30M patients with their fibril composition determined as either type A or type B. Measurements of left ventricular (LV) dimensions and evaluation of systolic and diastolic function including speckle tracking derived strain were performed. Patients were grouped according to fibril type and sex. Multivariate linear regression was utilised to determine factors of significant impact on LV thickness.RESULTS: There was no significant difference in proportions of the two types of fibrils between men and women. In patients with type A fibrils, women had significantly lower median septal (p = 0.007) and posterior wall thicknesses (p = 0.010), lower median LV mass indexed to height (p = 0.008), and higher septal strain (p = 0.037), as compared to males. These differences were not apparent in patients with type B fibrils. Multiple linear regression analysis revealed that fibril type, sex and age all had significant impact on LV septal thickness.CONCLUSION: This study demonstrates a clear difference between sexes in the severity of amyloid heart disease in ATTR V30M amyloidosis patients. Even though type A fibrils were associated with more advanced amyloid heart disease compared to type B, women with type A fibrils generally developed less cardiac infiltration than men. The differences may explain the better outcome for liver transplanted late-onset female patients compared to males.
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| 4. |
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| 5. |
- Harms, Hendrik J., et al.
(författare)
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Association of right ventricular myocardial blood flow with pulmonary pressures and outcome in cardiac amyloidosis
- 2023
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Ingår i: JACC Cardiovascular Imaging. - : Elsevier. - 1936-878X .- 1876-7591. ; 16:9, s. 1193-1204
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Tidskriftsartikel (refereegranskat)abstract
- Background: Cardiac amyloidosis (CA) is a restrictive and infiltrative cardiomyopathy, characterized by increased biventricular filling pressures and low output. Symptoms are predominantly of right heart origin. The role of right ventricular (RV) myocardial blood flow (MBF) in CA has not been studied.Objectives: This study aimed to first associate RV MBF measured by using positron emission tomography (PET) with reference standards of RV pressures and then to explore its prognostic value in CA.Methods: Cardiac PET was performed at rest in 52 patients with CA and 9 healthy control subjects. MBF was quantified from the right and left ventricles by using 11C-acetate, 15O-water, or both (n = 25). RV pressure was measured invasively or by echocardiography. Associations between biventricular MBF toward symptoms, RV function, and outcome (death or acute heart failure) were studied in patients with CA.Results: MBF of the right ventricle (MBFRV) and the ratio of MBFRV and MBF of the left ventricle (MBFRV/LV) for the 2 tracers were significantly correlated (r > 0.92). MBFRV was directly correlated with RV systolic pressures with both tracers (P ≤ 0.005). MBFLV was inversely correlated with wall thickness (P < 0.0001). MBFRV/LV was significantly associated with N-terminal pro–B-type natriuretic peptide levels, New York Heart Association functional class, RV pressures, and RV systolic function (all; P < 0.001). Twenty-six cardiac events (25 deaths) occurred during follow-up (median 44 months). MBFRV/LV higher than 56% was associated with a diagnosis of pulmonary hypertension (AUC: 0.96 [95% CI: 0.91-1.00]; P < 0.0001); and predicted outcome with hazard ratio 9.0 (95% CI: 4.2-14.5), P < 0.0001).Conclusions: Measurements of MBFRV using PET are feasible, as confirmed with 2 different tracers. Imbalance between RV and LV myocardial perfusion is associated with increased RV load and adverse events in cardiac amyloidosis.
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| 6. |
- Hellman, Urban, 1966-, et al.
(författare)
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Transthyretin Glu54Leu - an unknown mutation within the Swedish population associated with amyloid cardiomyopathy and a unique fibril type
- 2019
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Ingår i: Scandinavian Journal of Clinical and Laboratory Investigation. - : Taylor & Francis. - 0036-5513 .- 1502-7686. ; 79:6, s. 372-376
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Tidskriftsartikel (refereegranskat)abstract
- For the first time, we report of a Swedish family of five individuals with a TTR Glu54Leu (p. Glu74Leu) mutation in the transthyretin gene. This mutation has been previously described a few times in the literature, but no phenotypic or clinical description has been done before. The most common mutation in the Swedish population is TTRVal30Met and is mostly found in the Northern part of Sweden. Interestingly, the TTRGlu54Leu mutation was found in the same endemic area. The main phenotype of the TTR Glu54Leu patients is severe cardiomyopathy, which resulted in heart transplantation for the index person. As previously seen for ATTR amyloidosis patients with mainly cardiomyopathy, the amyloid fibrils consisted of a mixture of full-length and fragmented TTR species. However, western blot analyses detected a previously unrecognized band, indicating that these patients may have a third, so far unrecognized, fibril composition type that is distinct from the usual type A band pattern.
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| 7. |
- Henein, Michael, et al.
(författare)
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Long mitral valve leaflets determine left ventricular outflow tract obstruction during exercise in hypertrophic cardiomyopathy
- 2016
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Ingår i: International Journal of Cardiology. - : Elsevier. - 0167-5273 .- 1874-1754. ; 212, s. 47-53
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Development of left ventricular outflow tract obstruction (LVOTO) in patients with hypertrophic cardiomyopathy (HCM) is important for explaining symptoms and designing management. LVOTO is mostly caused by a combination of septal hypertrophy and systolic anterior movement of the mitral valve (SAM). The aim of the present study was to determine predictors of exercise induced LVOTO in a group of HCM patients.METHODS: We performed supine exercise Doppler echocardiography, including measurements of LV morphology and function and anterior mitral leaflet length, in 51 mildly symptomatic HCM (septal thickness≥15mm) and compared them with 50 healthy controls. Measurements were made at 1) rest, 2) Valsalva maneuver, 3) peak exercise and 4) post exercise. LVOTO was diagnosed as a LVOT gradient of >30mmHg at rest, after Valsalva and after exercise or ≥50mmHg at peak exercise.RESULTS: All patients stopped exercise because of exhaustion. 35% of the patients had resting LVOTO and 48% during Valsalva. At peak exercise, only 37% had LVOTO, who increased to 64% post exercise. Patients who developed LVOTO at peak exercise were more prone to continue having it post exercise (p<0.001), to have attenuated systolic blood pressure rise (p=0.011) and to have long anterior mitral valve leaflets (p<0.001). Backward multiple regression analysis showed the anterior mitral leaflet length as the strongest single independent predictor (β=0.36, p=0.010) for increased LVOT velocities, followed by basal septal thickness.CONCLUSION: In patients with HCM, LV outflow tract obstruction seems to be relatively uncommon during exercise but rather occurring minutes after stopping exercise. Exercise LVOTO seems to be determined by long anterior mitral leaflets in addition to the well established septal hypertrophy.
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| 8. |
- Henein, Michael Y., et al.
(författare)
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Disease progression in cardiac morphology and function in heart failure : ATTR cardiac amyloidosis versus hypertensive left ventricular hypertrophy
- 2022
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Ingår i: Heart and Vessels. - : Springer. - 0910-8327 .- 1615-2573. ; 37, s. 1562-1569
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Transthyretin cardiac amyloidosis (ATTR-CA) is today more frequently recognized but the rate of progression of cardiac dysfunction is not well established. The aim of this study is to investigate the nature of cardiac structure and function changes, over time, in a retrospective cohort of ATTR-CA patients.METHODS: Fifty-one patients with ATTR-CA (mean age 78 ± 7 years, 30 females) were compared with 20 patients with heart failure but no amyloidosis (HFnCA) (mean age 76 ± 7 years, 5 females), all with septal thickness > = 14 mm. All patients underwent DPD scintigraphy and an echocardiogram (Echo 2) which was compared with a previous echocardiographic examination (Echo 1), performed at least 3 years before.RESULTS: Over the follow-up period, the interventricular septal thickness (IVST) and relative wall thickness (RWT) in ATTR-CA increased from 16 (4) to 18 (5) mm and from 0.51 (0.17) to 0.62 (0.21) respectively, p < 0.001 for both, by a mean increase of 0.4 mm/year and 0.03 mm/year, (p = 0.009 and p = 0.002 compared with HFnCA), respectively. RWT > 0.45 (AUC = 0.77) and RELAPS > 2.0 (AUC 0.86) both predicted positive DPD diagnosis for ATTR-CA.CONCLUSION: In ATTR-CA patients, the overtime-increase in RWT and IVST was worse than that seen in patients with heart failure but no cardiac amyloidosis. Also, RWT and relative apical sparing predicted diagnosis of ATTR-CA, thus could strengthen the use of follow-up echocardiographic findings as red flag for the diagnosis of ATTR-CA.
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| 9. |
- Henein, Michael Y., et al.
(författare)
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Reduced left atrial myocardial deformation irrespective of cavity size : a potential cause for atrial arrhythmia in hereditary transthyretin amyloidosis
- 2018
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Ingår i: Amyloid. - : TAYLOR & FRANCIS LTD. - 1350-6129 .- 1744-2818. ; 25:1, s. 46-53
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Tidskriftsartikel (refereegranskat)abstract
- Background: Cardiac amyloidosis (CA) is a myocardial disease and commonly under-diagnosed condition. In CA patients, atrial fibrillation might occur in the absence of left atrial (LA) enlargement.Objectives: The aim of this study is to assess LA size and function, and its relationship with atrial arrhythmia in patients with hereditary transthyretin amyloidosis (ATTR).Methods: Forty-six patients with confirmed ATTR amyloidosis on abdominal biopsy were studied. Assessment with 2D echocardiography and 2D strain showed 31 patients had increased LV wall thickness (LVWT) (septal thickness >12mm), and 15 had normal LVWT. In addition to conventional measurements, LV and LA global longitudinal strain (GLS%) and strain rate (SR) were obtained. Western blot analysis was done to assess fibril type. ATTR patients with increased LVWT were compared with 23 patients with hypertrophic cardiomyopathy (HCM) and 31 healthy controls. ATTR amyloidosis patients also underwent 24hour Holter monitoring to determine the presence of atrial arrhythmia.Results: Atrial deformation during atrial systole was reduced in ATTR amyloidosis patients with increased LVWT independent of LA size and in contrast to HCM. Twenty of the ATTR amyloidosis patients (54%) had ECG evidence of significant atrial arrhythmic events. LA strain rate, during atrial systole, was the only independent predictor of atrial arrhythmia (=3.28, p=.012).Conclusion: In ATTR cardiomyopathy with increased LVWT, LA myocardial function is abnormal, irrespective of atrial cavity size. Reduced LA myocardial SR during atrial systole, irrespective of cavity volume, E/e and LV deformation, is also a strong predictor for atrial arrhythmic events.
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| 10. |
- Lindmark, Krister, et al.
(författare)
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Prevalence of wild type transtyrethin cardiac amyloidosis in a heart failure clinic
- 2021
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Ingår i: ESC Heart Failure. - : John Wiley & Sons. - 2055-5822. ; 8:1, s. 745-749
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Tidskriftsartikel (refereegranskat)abstract
- Aims: Wild type transthyretin amyloidosis (ATTRwt) has gained interest during recent years due to better diagnostic tools and the emergence of treatment options. Little is known about the prevalence of the disease. We aimed to investigate the prevalence in a heart failure population with myocardial hypertrophy.Methods and results: All patients with an ICD code of heart failure living within the catchment area of Umeå University hospital and intraventricular septum >14 mm were offered screening with 3,3‐diphosphono‐1,2‐propanodicarboxylic acid (DPD) scan and a clinical work up. Out of 2238 patients with heart failure, 174 patients were found to have a septum >14 mm. Ten patients were already diagnosed with hereditary ATTR cardiomyopathy, 12 patients had ATTRwt cardiomyopathy, 12 patients had known HCM, one patient had AL amyloidosis, and four patients had already undergone a negative DPD scan (DPD uptake grade 0 and 1) within the last 3 years. This left 134 patients who we tried to contact for screening, but 48 patients had either died or declined to participate. Out of 86 screened patients, 13 had a DPD uptake of grade 2 or 3 without other amyloid disease making the total number of patients with ATTRwt in this population 25.Conclusions: Approximately 20% of investigated patients in a cohort with heart failure and increased myocardial wall thickness has ATTRwt. Calculated for the whole population of heart failure patients, the prevalence is just over 1.1%. Comparing this number to the total population would give an estimated prevalence of 1:6000.
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