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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 amyloid cardiomyopathy (ATTR‐CM) is an increasingly recognized cause of heart failure. A total of 3–4% of individuals of African descent carry a TTR gene mutation encoding the p.(V142I) variant, a powerful risk factor for development of variant ATTR‐CM (ATTRv‐CM); this equates to 1.6 million carriers in the United States. We undertook deep phenotyping of p.(V142I)‐ATTRv‐CM and comparison with wild‐type ATTR‐CM (ATTRwt‐CM). Methods and results: A retrospective study of 413 patients with p.(V142I) ATTRv‐CM who attended the UK National Amyloidosis Centre (NAC) was conducted. Patients underwent evaluation at time of diagnosis, including clinical, echocardiography, and biomarker analysis; a subgroup had cardiac magnetic resonance (CMR) imaging. A total of 413 patients with ATTRwt‐CM, matched for independent predictors of prognosis (age, NAC Stage, decade of first presentation), were used as a comparator group. At time of diagnosis, patients with ATTRv‐CM had significant functional impairment by New York Heart Association classification (NHYA class ≥ III; 38%) and 6‐min walk test distance (median 276 m). Median 5‐year survival in ATTRv‐CM patients was 31 versus 59 months in matched patients with ATTRwt‐CM (p < 0.001). Patients with ATTRv‐CM had significant impairment of functional parameters by echocardiography including biventricular impairment, high burden of regurgitant valvular disease and low cardiac output. Multivariable analysis revealed the prognostic importance of right ventricular dysfunction. CMR and histological analysis revealed myocyte atrophy and widespread myocardial infiltration in ATTRv‐CM. Conclusion: p.(V142I)‐ATTRv‐CM has an aggressive phenotype characterized by myocyte loss and widespread myocardial infiltration which may account for frequent biventricular failure and poor prognosis in this ATTR‐CM genotypic subgroup. [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 Methods and results Conclusions Cardiac amyloidosis (CA) is characterized by deposition of amyloid fibrils within the extracellular space, causing disarray of the myocardial structure and capillary architecture. This study aims to characterize the prevalence of microvascular obstruction (MVO) in patients with CA and to assess the association between MVO and prognosis.The study population comprised 800 patients, of which 400 had light‐chain CA (AL‐CA) and 400 had transthyretin CA (ATTR‐CA). MVO was present in 221 (27.6%) patients, and more common in ATTR‐CA than AL‐CA (124 [56.1%] vs. 97 [43.9%], p = 0.033). Patients with MVO had a more severe cardiac phenotype evidenced by higher N‐terminal pro‐brain natriuretic peptide (3516 ng/L [1944–6247] vs. 2508 ng/L [1203–5752], p < 0.001), worse global longitudinal strain (−10.5% [−12.6; −7.9] vs. −12.0% [−16.0; −8.9], p < 0.001), and higher extracellular volume (56% [51–61] vs. 50% [45–57], p < 0.001). Patients with AL‐CA and MVO had a higher serum troponin (86 ng/L [47–148] vs. 59 ng/L [44–78], p < 0.001), and higher T2 (53 ms [50–56] vs. 50 ms [48–52], p < 0.001), but lower extracellular volume (55% [50–60] vs. 58% [53–61], p = 0.008) and lower indexed myocyte cell volume (48.6 g/m2 [41.1–59.8] vs. 55.7 g/m2 [47.5–68.4], p < 0.001) than patients with ATTR‐CA and MVO. MVO was associated with an increased risk of mortality in the overall population (hazard ratio [HR] 1.28, 95% confidence interval [CI] 1.03–1.59, p = 0.025), and the subgroup with AL‐CA (HR 1.59, 95% CI 1.17–2.17, p = 0.003) but not ATTR‐CA (HR 1.04, 95% CI 0.77–1.40, p = 0.814).Microvascular obstruction is common in CA and is related to markers of amyloid infiltration. MVO is associated with an increased risk of mortality in AL‐CA, but not in ATTR‐CA. This reflects the intrinsic differences in disease biology between these two forms of CA, with MVO likely related to multiple myocardial processes, amyloid infiltration, oedema and myocyte death. [ABSTRACT FROM AUTHOR]