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Aims: Transthyretin cardiac amyloidosis (ATTR‐CA) is stratified into prognostic categories using the National Amyloidosis Centre (NAC) staging system. The aims of this study were to further expand the existing NAC staging system to incorporate an additional disease stage that would identify patients at high risk of early mortality. Methods and results: The traditional NAC staging system (stage 1: N‐terminal pro‐B‐type natriuretic peptide [NT‐proBNP] ≤3000 ng/L and estimated glomerular filtration rate [eGFR] ≥45 ml/min; stage 3: NT‐proBNP >3000 ng/L and eGFR <45 ml/min; stage 2: remainder) was expanded by the introduction of a new stage 4 (defined as NT‐proBNP ≥10 000 ng/L irrespective of eGFR) and studied in 2042 patients. The optimal NT‐proBNP cut‐point was established using time‐dependent receiver operating characteristic curves in the subgroup of patients with NAC stage 3 disease. Mortality at 1 year according to NAC stage was 2.3% (n = 20/886) for stage 1, 8.8% (n = 62/706) for stage 2, 10.4% (n = 28/270) for stage 3, and 30.6% (n = 55/180) for stage 4 (log‐rank p < 0.001). After adjustment for age, mortality hazard for stage 4 was >15‐fold higher than that of stage 1 (hazard ratio [HR] 15.5; 95% confidence interval [CI] 9.3–26.1) and >3‐fold higher than that of stage 3 (HR 3.4; 95% CI 2.2–5.4). The increased risk of early mortality was consistent across the different genotypes and subclasses of patients based on the severity of heart failure symptoms and echocardiographic parameters. Conclusions: The proposed modification of the NAC staging system identifies patients with ATTR‐CA at a high risk of early mortality, who may benefit from a more intensive treatment strategy, and who are most likely to experience an event early in the course of a clinical trial. [ABSTRACT FROM AUTHOR]

Aims: Transthyretin cardiac amyloidosis (ATTR‐CA) is an infiltrative cardiomyopathy that commonly presents with concomitant chronic kidney disease. Albuminuria is common in heart failure and associated with worse outcomes, but its prevalence and relationship to outcome in ATTR‐CA remains unclear. Methods and results: A total of 1181 patients with ATTR‐CA were studied (mean age 78.1 ± 7.9 years; 1022 [86.5%] male; median estimated glomerular filtration rate 59 ml/min/1.73m2 [interquartile range: 47–74]). Albuminuria was present in 563 (47.7%) patients (499 [88.6%] with microalbuminuria and 64 [11.4%] with macroalbuminuria). Patients with albuminuria had a more severe cardiac phenotype evidenced by higher serum cardiac biomarkers (median N‐terminal pro‐B‐type natriuretic peptide [NT‐proBNP]: 4027 ng/L [2173–6889] vs. 1851 ng/L [997–3209], p < 0.001; median troponin T: 69 ng/L [46–101] vs. 48 ng/L [34–68], p < 0.001) and worse echocardiographic indices of systolic (longitudinal strain: −10.0 ± 3.6% vs. −11.6 ± 3.8%, p < 0.001) and diastolic function (E/e′: 17.5 ± 6.4 vs. 16.4 ± 6.7, p < 0.001) than those with a normal urinary albumin to creatinine ratio (UACR). Microalbuminuria and macroalbuminuria were independently associated with mortality in the overall population (hazard ratio [HR] 1.47, 95% confidence interval [CI] 1.13–1.92, p = 0.005 and HR 1.87, 95% CI 1.15–3.05, p = 0.012, respectively). In a subgroup of patients (n = 349) without concomitant hypertension, diabetes mellitus or chronic kidney disease, albuminuria was also associated with mortality (HR 2.98, 95% CI 1.72–5.17, p < 0.001). At 12 months, 330 patients had a repeat UACR measurement; those in whom UACR increased by 30% or more (n = 148, 44.8%) had an increased risk of mortality (HR 1.84, 95% CI 1.06–3.19, p = 0.030). Conclusions: Albuminuria is common in patients with ATTR‐CA, and more prevalent in those with a more severe cardiac phenotype. Albuminuria at diagnosis and a significant increase in UACR during follow‐up are associated with mortality. [ABSTRACT FROM AUTHOR]

Aims The aims of this study were to assess prescription patterns, dosages, discontinuation rates, and association with prognosis of conventional heart failure medications in patients with transthyretin cardiac amyloidosis (ATTR-CA). Methods and results A retrospective analysis of all consecutive patients diagnosed with ATTR-CA at the National Amyloidosis Centre between 2000 and 2022 identified 2371 patients with ATTR-CA. Prescription of heart failure medications was greater among patients with a more severe cardiac phenotype, comprising beta-blockers in 55.4%, angiotensin-converting enzyme inhibitors (ACEis)/angiotensin II receptor blockers (ARBs) in 57.4%, and mineralocorticoid receptor antagonists (MRAs) in 39.0% of cases. During a median follow-up of 27.8 months (interquartile range 10.6–51.3), 21.7% had beta-blockers discontinued, and 32.9% had ACEi/ARBs discontinued. In contrast, only 7.5% had MRAs discontinued. A propensity score-matched analysis demonstrated that treatment with MRAs was independently associated with a reduced risk of mortality in the overall population [hazard ratio (HR) 0.77 (95% confidence interval (CI) 0.66–0.89), P <.001] and in a pre-specified subgroup of patients with a left ventricular ejection fraction (LVEF) >40% [HR 0.75 (95% CI 0.63–0.90), P =.002]; and treatment with low-dose beta-blockers was independently associated with a reduced risk of mortality in a pre-specified subgroup of patients with a LVEF ≤40% [HR 0.61 (95% CI 0.45–0.83), P =.002]. No convincing differences were found for treatment with ACEi/ARBs. Conclusion Conventional heart failure medications are currently not widely prescribed in ATTR-CA, and those that received medication had more severe cardiac disease. Beta-blockers and ACEi/ARBs were often discontinued, but low-dose beta-blockers were associated with reduced risk of mortality in patients with a LVEF ≤40%. In contrast, MRAs were rarely discontinued and were associated with reduced risk of mortality in the overall population; but these findings require confirmation in prospective randomized controlled trials. [ABSTRACT FROM AUTHOR]

Aims To perform evaluation of widely embraced bone scintigraphy-based non-biopsy diagnostic criteria (NBDC) for ATTR amyloid cardiomyopathy (ATTR-CM) in clinical practice, and to refine serum free light chain (sFLC) ratio cut-offs that reliably exclude monoclonal gammopathy (MG) in chronic kidney disease. Methods and results A multi-national retrospective study of 3354 patients with suspected or histologically proven cardiac amyloidosis (CA) referred to specialist centres from 2015 to 2021; evaluations included radionuclide bone scintigraphy, serum and urine immunofixation, sFLC assay, eGFR measurement and echocardiography. Seventy-nine percent (1636/2080) of patients with Perugini grade 2 or 3 radionuclide scans fulfilled NBDC for ATTR-CM through absence of a serum or urine monoclonal protein on immunofixation together with a sFLC ratio falling within revised cut-offs incorporating eGFR; 403 of these patients had amyloid on biopsy, all of which were ATTR type, and their survival was comparable to non-biopsied ATTR-CM patients (p = 0.10). Grade 0 radionuclide scans were present in 1091 patients, of whom 284 (26%) had CA, confirmed as AL type (AL-CA) in 276 (97%) and as ATTR-CM in only one case with an extremely rare TTR variant. Among 183 patients with grade 1 radionuclide scans, 122 had MG of whom 106 (87%) had AL-CA; 60/61 (98%) without MG had ATTR-CM. Conclusion The NBDC for ATTR-CM are highly specific [97% (95% CI 0.91-0.99)] in clinical setting, and diagnostic performance was further refined here using new cut-offs for sFLC ratio in patients with CKD. A grade 0 radionuclide scan all but excludes ATTR-CM but occurs in most patients with AL-CA. Grade 1 scans in patients with CA and no MG are strongly suggestive of early ATTR-type, but require urgent histologic corroboration. [ABSTRACT FROM AUTHOR]

Women with a previous fetal demise have a 2–20 fold increased risk of another stillbirth in a subsequent pregnancy when compared to those who have had a live birth. Despite this, there is limited research regarding the management and outcomes of subsequent pregnancies. This study was conducted to accurately quantify the chances of a woman having a healthy subsequent pregnancy after a pregnancy loss. A retrospective study was conducted at a tertiary-level unit between March 2019 and April 2021. We collected data on all women with a history of previous fetal demise attending a specialized perinatal history clinic and compared the risk of subsequent stillbirth to those with a normal pregnancy outcome. Outcome data included birth outcome, obstetric and medical complications, gestational age and birth weight and mode of delivery. Those who had healthy subsequent pregnancies were compared with those who experienced adverse outcomes. A total of 101 cases were reviewed. Ninety-six women with subsequent pregnancies after a history of fetal demise from 16 weeks were included. Seventy-nine percent of women (n = 76) delivered a baby at term, without complications. Overall, 2.1% had repeat pregnancy losses (n = 2) and 2.1% delivered babies with fetal growth restriction (n = 2). There were no cases of abruption in a subsequent pregnancy. Eighteen neonates were delivered prematurely (18.4%), 15 of these (83.3%) were due to iatrogenic causes and three (16.7%) were spontaneous. In univariable logistic regression analyses, those with adverse outcomes in subsequent pregnancies had greater odds of pre-eclampsia (Odds ratio *(OR) = 3.89, 95% CI = 1.05–14.43, p =.042) and fetal growth restriction (OR = 4.58, 95% CI = 1.41–14.82, p = 0.011) in previous pregnancies compared to those with healthy outcomes. However, in multivariable logistic regression analyses, neither variable had a significant odds ratio (OR = 2.03, 95% CI = 0.44–9.39, p =.366 and OR = 3.42, 95% CI = 0.90 − 13.09, p =.072 for pre-eclampsia and FGR, respectively). Four in five women had a healthy subsequent pregnancy. This is a reassuring figure for women when contemplating another pregnancy, particularly if cared for in a specialist clinic. [ABSTRACT FROM AUTHOR]

Aims To assess the ability of cardiovascular magnetic resonance (CMR) to (i) measure changes in response to chemotherapy; (ii) assess the correlation between haematological response and changes in extracellular volume (ECV); and (iii) assess the association between changes in ECV and prognosis over and above existing predictors. Methods and results In total, 176 patients with cardiac AL amyloidosis were assessed using serial N-terminal pro-B-type natriuretic peptide (NT-proBNP), echocardiography, free light chains and CMR with T1 and ECV mapping at diagnosis and subsequently 6, 12, and 24 months after starting chemotherapy. Haematological response was graded as complete response (CR), very good partial response (VGPR), partial response (PR), or no response (NR). CMR response was graded by changes in ECV as progression (≥0.05 increase), stable (<0.05 change), or regression (≥0.05 decrease). At 6 months, CMR regression was observed in 3% (all CR/VGPR) and CMR progression in 32% (61% in PR/NR; 39% CR/VGPR). After 1 year, 22% had regression (all CR/VGPR), and 22% had progression (63% in PR/NR; 37% CR/VGPR). At 2 years, 38% had regression (all CR/VGPR), and 14% had progression (80% in PR/NR; 20% CR/VGPR). Thirty-six (25%) patients died during follow-up (40 ± 15 months); CMR response at 6 months predicted death (progression hazard ratio 3.82; 95% confidence interval 1.95–7.49; P < 0.001) and remained prognostic after adjusting for haematological response, NT-proBNP and longitudinal strain (P < 0.01). Conclusions Cardiac amyloid deposits frequently regress following chemotherapy, but only in patients who achieve CR or VGPR. Changes in ECV predict outcome after adjusting for known predictors. [ABSTRACT FROM AUTHOR]