Jurnal Internasional Pementasan jantung AL amiloidosis diperbarui menggunakan BNP

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Jurnal Internasional Pementasan jantung AL amiloidosis diperbarui menggunakan BNP

The inability to carry out gold standard testing for cardiac involvement in amyloidosis in the light chain immunoglobulin (AL amyloidosis) remains a barrier in many centers because they try to identify and predict high-risk patients quickly. In this edition of Blood Lilleness and colleagues sought to renew the Mayo 2004 heart staging system by examining utilities for replacing established pro-brain N-terminal peptide peptides (NT-proBNP)) with more brain natriuretic peptides (BNP) available. 1 Importantly, the Boston University (BU) staging system defined in their article was built on a more contemporary cohort that was treated in an era where proteasome inhibitors were now the mainstay of first-line therapy, and more patient selection strictly optimized the use of high-dose chemotherapy and autologous stem cell transplantation.

Severity of cardiac involvement remains the most important prognostic factor in AL amyloidosis. Despite advances in therapy, many patients have never lived long enough to benefit from this improvement due to early heart death. Determination of faster cardiac involvement helps identify those at high risk, thus providing an opportunity to initiate a more aggressive supportive care strategy and even modify the chemotherapy approach given. Initial work by the group at Mayo formed the first tool that can be widely applied to the risk of patient stratification. However, its dependence on NT-proBNP does limit its usefulness because many sites cannot run tests. Even though the BNP is more available, it cannot act directly as a substitute, hence the importance of the work presented by Lilleness et al. 2

In the study of Lilleness et al, the first step was to use a derivation cohort. to identify BNP levels that are most correlated with NT-proBNP levels of 332 pg / mL specified in the original Mayo criteria. 3 Second, a cohort is used to determine the indication of a BNP cutoff indication of cardiac involvement. Importantly, the authors define the cutoff by incorporating modern diagnoses, including cardiac magnetic resonance imaging (MRI) and more detailed echocardiographic criteria that are now commonly used in practice but not captured in 2005 consensus criteria. 4 That reflects a broader and more clinically relevant spectrum of cardiac involvement known to occur in AL amyloidosis.

Recognizing the relative interchangeability of cardiac troponin I (TnI) and troponin T (TnT) established in original Mayo publications, the authors chose the threshold of TnI from 0.1 ng / mL as a partner for BNP vs. NT-proBNP analysis. By examining a cohort of 250 patients who were evaluated sequentially who had NT-proBNP and BNP levels taken at diagnosis, an 81 pg / mL BNP threshold was identified as a match for the NT-proBNP level of 332 pg / mL recorded in the original Mayo Criteria 2004. Using the same derivation cohort, the authors then determined BNP and NT-proBNP thresholds that correlated with cardiac involvement. Interestingly, the same BNP limit of 81 pg / mL is a predictive light chain heart deposition. In contrast, the NT-proBNP limit of 288 pg / mL was determined as an indication of cardiac involvement, which was slightly lower than the level used for stratification in the Mayo phasing system. This may be related to preliminary studies designed primarily around survival rather than cardiac involvement and carried out in an era without extensive cardiac MRI availability. 4 Thus, these two values ​​may be useful as an initial screening at diagnosis to predict whether the heart might be involved and request more detailed examination if needed.

The authors acknowledge the variables of kidney metabolism from these two biomarkers, with NT -proBNP which is more dependent on the kidneys for cleansing. 5 They hypothesize that BNP might actually be superior in setting stage III or greater chronic kidney disease (CKD) in predicting cardiac involvement and that NT-proBNP might be more beneficial in stage II or lower CKD. In their analysis, the authors concluded that the latter turned out to be true, with NT-proBNP becoming more sensitive in patients with minimal or no renal impairment. However, in those with impaired renal function, both biomarkers were equally valid even at different thresholds: 427 pg / mL for BNP and 2930 pg / mL for NT-proBNP. Although both tests appear to be reasonable screening strategies for cardiac involvement (based on patient kidney function), one must consider this important nuance when applying data in the clinic.

Derivation groups are made using patients diagnosed sequentially. for 6 months with a maximum possible follow-up of only 2 years. Thus, to establish the prognostic utility of the BU staging system, the authors examined the second complementary cohort with 10 years of follow-up. Using a larger data set of more than 1000 patients, the authors were able to show that the BU staging system well classifies patients based on overall survival. Furthermore, consistent with the latest publication identifying patients with very high risk based on a marked increase in NT-proBNP levels (> 8500 pg / mL), 6 an additional BNP threshold of 700 pg / mL was specified in the BU staging system to determine patients with advanced stage IIIb disease. It is remarkable that, even though the BU staging system well distinguishes groups in a manner similar to the Mayo staging system, the survival estimates for each risk group are much longer (see table ). Stage I patients are expected to live for more than 10 years. Even in patients with advanced stage III disease, around 20% of them can also reach 10 milestones this year. Because of the more contemporary complementary cohort, results reflect the progress we experience with modern treatment methods for patients with AL amyloidosis. Although therapy for these patients continues to develop, there is hope that if sufficient therapy is given and a sufficient clone response is achieved, long-lasting remission with organ response can be achieved, even in patients with advanced disease.

Median overall survival with the heart staging system

The authors acknowledge several important limitations of this study. The main limitation is the lack of data using BNP as a marker of heart response after treatment. The NT-proBNP criterion for cardiac response remains the staging system that is best described and validated. 7 Thus, the system will continue to have an important role in management and follow-up, especially in clinical trial settings. Therefore, the data presented in the Lilleness et al article guarantees future research to validate BU systems that are proposed prospectively and to examine the usefulness of the BNP in response assessment.

Overall, research by Lilleness et al is important because it addresses very practically faced by many laboratories when they did not have a gold standard test to identify high-risk patients with AL amyloidosis. This is a step towards validating the use of BNP in this stage of the disease. In addition, he rebuilt these 2 biomarker utilities in a more contemporary cohort that was treated in the era of new agents. Ultimately, this may be a pathway for more accessible testing modalities that help doctors with early diagnosis and better characterization of their patients.


  • Disclosure of conflicts of interest: The author has received an honorarium from Amgen, Celgene, Takeda, and Janssen.

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