Data regarding renal involvement in patients with hereditary transthyretin (ATTRv) amyloidosis are scarce and the natural course of chronic kidney disease (CKD) in this population remains unclear. This observational study, including adult patients diagnosed with ATTRv amyloidosis at the French Reference Centre for Cardiac Amyloidosis, investigated renal function outcome and its determinants. Multivariable logistic regression models identified factors associated with CKD at baseline. Determinants of the change in estimated glomerular filtration rate (eGFR) over 24 months of follow-up were assessed with a multivariable linear mixed-effects model. In total, 232 patients (78 women [34%], mean age: 64 years) with ATTRv amyloidosis were classified on the basis of their TTR variants: ATTRV122I (37%), ATTRV30M (29%), and other variants (34%). Median baseline eGFR was 78 ml/min/1.73 m2. Seventy-two patients (31%) had an eGFR below 60 ml/min/1.73m2 and 27/137 patients (20%) had significant proteinuria (urine protein/creatinine ratio ≥30 mg/mmol). Renal biopsy, performed in four cases, found typical Congo red-positive and TTR-labelled amyloid deposits in all cases. Older age (OR 1.07, p < .001) and a prior history of hypertension (OR 2.09, p = .04) were associated with a higher prevalence of CKD at baseline, whereas higher left ventricular global longitudinal strain (LVGLS) (OR 0.83, p < .001) was associated with a lower prevalence. The estimated change in eGFR was -7.12 [-9.61, -4.63] and -8.21 [-10.81, -5.60] ml/min/1.73 m2 after 12 and 24 months of follow-up, respectively. eGFR decline was independently associated with older age ((67-74], coefficient= -14.35 mL/min/1.73 m2, p < .01, >74, coefficient = -22.93 mL/min/1.73 m2, p < .001, versus <56), ATTRV122I (coefficient = -17.17 mL/min/1.73m2, p < .01, versus ATTRV30M) and LVGLS (coefficient = 1.22, p < .01). These data suggest that CKD is a common finding in patients with ATTRv amyloidosis, and that eGFR decline is rapid during the first year of evaluation. Older age, lower LVGLS and ATTRV122I were associated with a worse renal outcome. Further studies are now needed to evaluate effects of new targeted therapies on long term renal function.

The link between transthyretin cardiac amyloidosis (CATTR), and cerebral ischemic events (CIE) has only been hinted at till now, impeding progress in patient management. We seek to evaluate the frequency and characteristics of CIE in Afro-Caribbean patients followed for CATTR at our institution. In this single-center retrospective observational study, Afro-Caribbean patients followed for CATTR between July 2005 and October 2019 were included. Occurrence of CIE was investigated, and their cardioembolic origin determined. Analysis of patient characteristics was conducted according to CIE and CATTR profiles. Overall, 120 CATTR patients were included: 17 wild-type ATTR (14.2%), 73 ATTR-V122I (60.8%), and 22 ATTR-I107V (18.3%). Thirty-six patients (30.0%) presented with CIE, including three transient ischemic attacks and 33 permanent ischemic strokes (75.8% with a cardioembolic pattern). CIE was concomitant with CATTR diagnosis in 16 (16/36: 44.4%) patients, while 14 patients (14/36: 38.9 %) experienced CIE over a median CATTR follow-up of 2.0 years (min-max range: 0.8-4.4 years). CATTR-CIE patients presented with atrial fibrillation (66.7%), left atrial enlargement (77.8%), a CHA2DS2-VASc ≥ 3 (97.2%) and a high anticoagulant intake (75.0%). Multivariate analysis retained only a high CHA2DS2-VASc score as an independent predictor of CIE risk (Hazard Ratio [95% CI]: 12.03 [1.62-89.24]). Concomitant CIE, and CATTR diagnosis, potentially carries a worse prognosis. A CHA2DS2-VASc score ≥3 seems to be a strong and independent predictive factor of CIE in CATTR patients. Further studies are needed to assess the efficacy and timeliness of anticoagulation in CATTR patients, independently of atrial fibrillation.

Objective: To characterize the changing spectrum of amyloidosis classes, as well as patient demographics, at a major US referral centre. Patients and methods: A retrospective analysis was conducted of all referrals to the Amyloidosis Centre at Boston University and Boston Medical Centre over the last 3 decades. Results: A total of 3987 new patients with amyloidosis were evaluated between 1990 and 2018 with the average number of new cases per year increasing 2.5-fold during this period. Systemic immunoglobulin light-chain (AL) amyloidosis decreased in proportion with each decade from 77% to 69% to 50% of new cases. Meanwhile, ATTR amyloidosis increased from 12% to 16% to 29%, predominately due to more diagnosis of ATTRwt and ATTRV122I amyloidosis. Gender and race profile differences, while changing over the observed time period, persisted among amyloidosis patients. Conclusion: Amyloid diseases are more widely recognized and classes of amyloidosis, including ATTRwt and ATTRV122I, once considered rare are now increasingly diagnosed. These data likely reflect a national trend of increased amyloidosis awareness facilitated by accessible diagnostic approaches, emerging treatments, and coordinated educational initiatives. ClinicalTrials.gov identifier: NCT00898235.

Non-invasive imaging to diagnose and quantify amyloid load, progression, and response to treatment are central for the care of patients with cardiac amyloidosis. 18Fluorine-labeled sodium fluoride (18F-NaF) is a widely available radioisotope and PET imaging allows for absolute quantification of tracer uptake. Patients with biopsy-proven transthyretin (ATTR-CA) and light-chain cardiac amyloidosis (AL) (3 ATTRwt, 2 ATTRV122I, 2 AL) and controls (n = 5), underwent 18F-NaF PET imaging. Scans were assessed visually for radiotracer uptake and analyzed using standard uptake values in the entire myocardium (SUVm) and in a 17-segment cardiac model. Wilcoxon rank-sum tests were used for statistical analyses. Qualitative 18F-NaF uptake was absent in controls and AL patients. There was qualitative 18F-NaF uptake in ATTR-CA patients, with slightly increased uptake in wild-type patients. SUVm for controls and AL patients overlapped at 0.8(0.4-0.9) and 0.95(0.9-1.0), respectively (P = 0.434). At 1.5(1.4-1.7), SUVm for ATTR-CA patients was ≈1.5*SUVm of controls (P = 0.012) and AL patients (P = 0.078). While there was diffuse 18F-NaF myocardial in ATTR-CA patients, the degree of uptake varied according to cardiac segment. 18F-NaF PET effectively imaged and differentiated ATTR-CA patients. Semi-automatic software enabled quantification of radiotracer uptake and regional distribution. 18F-NaF PET may be useful for disease monitoring and localizing amyloid deposition in ATTR-CA patients.

Amyloidosis is a group of conditions characterized by the accumulation of amyloid deposits in various tissues. Among these disorders, ATTR amyloidosis occurs either with or without a TTR pathogenic variant. Treatment for amyloidosis depends on the subtype, which is often identified through a tissue biopsy followed by liquid chromatography tandem mass spectrometry (LC-MS/MS). Genetic testing may be done to confirm these results for patients with ATTR amyloidosis; however, the necessity of genetic testing after LC-MS/MS has not been evaluated. A retrospective review identified 153 patients diagnosed with biopsy-proven ATTR amyloidosis, and 56 of these patients underwent both genetic testing and LC-MS/MS. LC-MS/MS and proteomics correctly reported the mutant peptide and heterozygosity in 47/56 (84%) cases. It failed to identify two individuals who were homozygous for the ATTRV122I mutation and failed to detect the following mutations in six other individuals: ATTRA19D, ATTRF44L, ATTRT60A, ATTRI68L and ATTRV122I. Therefore, LC-MS/MS is not sufficient to rule out a pathogenic mutation in cases of ATTR amyloid, and genetic testing should be performed in most cases of ATTR amyloidosis. Correct recognition of hereditary ATTR amyloidosis is important for estimating prognosis, proper familial counselling and guiding use of therapies, such as liver transplantation.