Biomarkers and Prediction of Prognosis in Transthyretin-Related Cardiac Amyloidosis: Direct Comparison of Two Staging Systems

Cappelli, Francesco; Martone, Raffaele; Gabriele, Martina; Taborchi, Giulia; Morini, Sofia; Vignini, Elisa; Allinovi, Marco; Gioia, Massimo Di; Bartolini, Simone; Mario, Carlo Di; Perfetto, Federico

doi:10.1016/j.cjca.2019.12.020

Cited by 27 publications

(27 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The NAC ATTR staging system displayed a better prognostic accuracy for ATTR CA than a classification system based on NT-proBNP and TnI. 110 In the article by Gillmore et al 85 patients being classified in the three stages at baseline was similar in both subgroups. Actually, patients with V122I ATTRv CA had slightly higher median NT-proBNP concentrations within stage II and III at baseline compared to ATTRwt CA, possibly reflecting a more advanced disease at diagnosis and/or a more aggressive disease phenotype.…”

Section: Mayo2004 66mentioning

confidence: 96%

“…recently devised a three‐stage classification system [National Amyloidosis Centre (NAC) ATTR staging system] for both ATTRwt and ATTRv CA using NT‐proBNP (cut‐off: 3000 ng/L) and GFR (cut‐off: 45 mL/min/1.73 m 2 ): 45% of patients were in stage I, 38% in stage II and 16% in stage III, with a median survival of 69.2, 46.7 and 24.1 months, respectively. The NAC ATTR staging system displayed a better prognostic accuracy for ATTR CA than a classification system based on NT‐proBNP and TnI 110 . In the article by Gillmore et al 85 .…”

Section: Biomarkers Of Cardiac Involvementmentioning

confidence: 99%

See 1 more Smart Citation

Use of biomarkers to diagnose and manage cardiac amyloidosis

Castiglione

Franzini

Aimo

et al. 2021

European J of Heart Fail

View full text Add to dashboard Cite

Amyloidoses are characterized by the tissue accumulation of misfolded proteins into insoluble fibrils. The two most common types of systemic amyloidosis result from the deposition of immunoglobulin light chains (AL) and wild-type or variant transthyretin (ATTRwt/ATTRv). Cardiac involvement is the main determinant of outcome in both AL and ATTR, and cardiac amyloidosis (CA) is increasingly recognized as a cause of heart failure. In CA, circulating biomarkers are important diagnostic tools, allow to refine risk stratification at baseline and during follow-up, help to tailor the therapeutic strategy and monitor the response to treatment. Among amyloid precursors, free light chains are established biomarkers in AL amyloidosis, while the plasma transthyretin assay is currently being investigated as a tool for supporting the diagnosis of ATTRv amyloidosis, predicting outcome and monitor response to novel tetramer stabilizers or small interfering RNA drugs in ATTR CA. Natriuretic peptides (NPs) and troponins are consistently elevated in patients with AL and ATTR CA. Plasma NPs, troponins and free light chains hold prognostic significance in AL amyloidosis, and are evaluated for therapy decision-making and follow-up, while the value of NPs and troponins in ATTR is less well established. Biomarkers can be usefully integrated with clinical and imaging variables at all levels of the clinical algorithm of systemic amyloidosis, from screening to diagnosis and prognosis, and treatment tailoring.

show abstract

Section: Mayo2004 66mentioning

confidence: 96%

Section: Biomarkers Of Cardiac Involvementmentioning

confidence: 99%

Use of biomarkers to diagnose and manage cardiac amyloidosis

Castiglione

Franzini

Aimo

et al. 2021

European J of Heart Fail

View full text Add to dashboard Cite

show abstract

“…At the time of diagnosis, prognosis of patients with ATTR-CM can be estimated by stratifying them into one of the three National Amyloidosis Centre (NAC) ATTR stages, according to the N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentration and Modification of Diet in Renal Disease estimated glomerular filtration rate (eGFR). 13,14 Median survival in Stage I, II, and III ATTR-CM is approximately 6, 4, and 2 years, respectively. 13 However, serial calculation of NAC ATTR stage in order to determine whether patients progress through the NAC stages during their disease course and if so whether an increase in NAC ATTR stage is of prognostic relevance has not previously been undertaken.…”

Section: Introductionmentioning

confidence: 99%

“…At the time of diagnosis, prognosis of patients with ATTR‐CM can be estimated by stratifying them into one of the three National Amyloidosis Centre (NAC) ATTR stages, according to the N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP) concentration and Modification of Diet in Renal Disease estimated glomerular filtration rate (eGFR) 13,14 . Median survival in Stage I, II, and III ATTR‐CM is approximately 6, 4, and 2 years, respectively 13 .…”

Section: Introductionmentioning

confidence: 99%

Disease progression in cardiac transthyretin amyloidosis is indicated by serial calculation of National Amyloidosis Centre transthyretin amyloidosis stage

Law¹,

Petrie

Chacko³

et al. 2020

ESC Heart Failure

View full text Add to dashboard Cite

Aims Cardiac transthyretin amyloidosis (ATTR-CM) is a progressive and fatal condition. Prognosis can be determined at diagnosis according to the National Amyloidosis Centre (NAC) transthyretin amyloidosis (ATTR) stage. We sought to examine how NAC ATTR stage changes during follow-up and whether it maintains its prognostic value throughout the disease course. Methods and results We performed a retrospective study of 945 patients with wild-type ATTR-CM (wtATTR-CM) or hereditary ATTR-CM associated with the V122I variant (V122I-hATTR-CM) who were diagnosed and serially evaluated at the UK NAC. Patients who commenced any disease-modifying therapy for amyloidosis were censored at the time of doing so. Landmark Kaplan-Meier survival analyses were performed at diagnosis (n = 945) and at 6 ± 1 (n = 432), 12 ± 3 (n = 562), and 24 ± 3 (n = 316) months and stratified by recalculated NAC ATTR stage at the relevant time point. Cox regression analyses were performed to assess the prognostic significance during follow-up of an increase in NAC ATTR stage from Stage I at diagnosis. Mortality in ATTR-CM was predicted by NAC ATTR stage at each time point [Stage II vs. I, hazard ratios (HRs) 1.95-2.67; P < 0.001; Stage III vs. II, HRs 1.64-2.25; P < 0.001-0.013]. An increase from NAC ATTR Stage I, which occurred in 21%, 32%, and 44% of evaluable patients at 6, 12, and 24 months of follow-up respectively, was highly predictive of ongoing mortality at each time point (HRs 2.58-3.22; P < 0.001) and in each genotypic subgroup (HRs 1.86-4.38; P < 0.05). Increase in NAC ATTR stage occurred earlier in V122I-hATTR-CM than in wtATTR-CM (43% vs. 27% at 12 months of follow-up; P = 0.003). Conclusions National Amyloidosis Centre ATTR stage predicts ongoing survival throughout the disease natural history in ATTR-CM, and an increase from NAC ATTR Stage I at diagnosis to a higher NAC ATTR stage predicts mortality throughout follow-up. Serial calculation of NAC ATTR stage suggests a more aggressive phenotype in V122I-hATTR-CM than in wtATTR-CM.

show abstract

“…We confirm that they each have moderate discriminatory ability in their current forms. A recent study comparing the 2 risk models in 175 ATTR-CM patients found that the UK model had better discrimination than the Mayo model ( 25 ). Our analysis found similar results, with the UK model performing slightly better than the Mayo model, although the difference was not significant.…”

Section: Discussionmentioning

confidence: 99%

Diuretic Dose and NYHA Functional Class Are Independent Predictors of Mortality in Patients With Transthyretin Cardiac Amyloidosis

Cheng

Levy

Vasbinder

et al. 2020

JACC: CardioOncology

View full text Add to dashboard Cite

BACKGROUND With increasing diagnoses and available treatment options for transthyretin amyloidosis cardiomyopathy (ATTR-CM), risk stratification of ATTR-CM patients is imperative. OBJECTIVES We hypothesized that diuretic dose and New York Heart Association (NYHA) functional class are independent predictors of mortality in ATTR-CM and would be incrementally additive to existent risk scores. METHODS Consecutive ATTR-CM patients referred to a single center were identified. Adjusted Cox proportional hazards models determined the association between diuretic dose (furosemide equivalent in mg/kg) at time of diagnosis and the primary outcome of all-cause mortality. The incremental value of adding diuretic dose and NYHA functional class to existing ATTR-CM risk scores was assessed for discrimination and calibration. RESULTS 309 patients were identified, with mean age 73.2 ± 9.8 years, 84.1% male, and 66% wild type. Daily mean diuretic dose was 0.6 ± 1.0 mg/kg and significantly associated with all-cause mortality (unadjusted hazard ratio: 2.12 per 1-mg/kg increase, [95% confidence interval: 1.71 to 2.61] and fully adjusted hazard ratio: 1.43 [95% confidence interval: 1.06 to 1.93]). Testing previously published ATTR risk scores, adding diuretic dose as categories (0 mg/kg, >0 to 0.5 mg/kg, >0.5 to 1 mg/kg, and >1 to 2 mg/kg) improved the area under the curve of the Mayo risk score from 0.693 to 0.767 and the UK risk score from 0.711 to 0.787 while preserving calibration. Adding NYHA functional class further improved the area under the curve to 0.798 and 0.816, respectively. CONCLUSIONS Diuretic dose and NYHA functional class are independent predictors of mortality in ATTR-CM patients and provide incremental value to existing ATTR-CM risk scores.

show abstract

Biomarkers and Prediction of Prognosis in Transthyretin-Related Cardiac Amyloidosis: Direct Comparison of Two Staging Systems

Cited by 27 publications

References 31 publications

Use of biomarkers to diagnose and manage cardiac amyloidosis

Use of biomarkers to diagnose and manage cardiac amyloidosis

Disease progression in cardiac transthyretin amyloidosis is indicated by serial calculation of National Amyloidosis Centre transthyretin amyloidosis stage

Diuretic Dose and NYHA Functional Class Are Independent Predictors of Mortality in Patients With Transthyretin Cardiac Amyloidosis

Contact Info

Product

Resources

About