title: Characterization and prediction of natriuretic peptide "nonresponse" during heart failure management: results from the ProBNP Outpatient Tailored Chronic Heart Failure (PROTECT) and the NT-proBNP-Assisted Treatment to Lessen Serial Cardiac Readmissions and Death (BATTLESCARRED) study.
abstract: Many proven heart failure (HF) therapies decrease N-terminal pro B-type natriuretic peptide (NT-proBNP) values over time, yet some patients have an NT-proBNP >1000 pg/mL following treatment, which is associated with poor outcomes. A total of 151 patients with left ventricular systolic dysfunction were treated with aggressive HF therapy in the ProBNP Outpatient Tailored Chronic Heart Failure (PROTECT) study. Clinical characteristics and NT-proBNP were measured at each visit during 10 months. In this post hoc analysis, biomarker nonresponse was defined as an NT-proBNP >1000 pg/mL and its relationship with echocardiographic and clinical characteristics and outcomes were explored. A risk model predictive of nonresponse was derived and externally validated. A rising NT-proBNP over time was associated with increased cardiovascular event rates while a decreasing NT-proBNP was associated with better clinical outcomes (58.2% vs 27.6%, P=.001). A higher percentage of time in biomarker response was associated with lower event rates (P<.001). Importantly, responders showed improved left ventricular remodeling parameters (all P<.001), while nonresponders did not. A risk model for predicting nonresponse had a C statistic of 0.82 (P<.001) and predicted outcomes well. Using data from the NT-proBNP-Assisted Treatment to Lessen Serial Cardiac Readmissions and Death (BATTLESCARRED) cohort, the risk score was validated for its ability to predict nonresponse (C statistic 0.73, P<.001). Serial changes in NT-proBNP inform risk for adverse outcome and are associated with prognostically meaningful metrics. Prediction of future NT-proBNP nonresponse to HF therapy is possible.
authors.affiliation: Cardiology Division, Massachusetts General Hospital, Boston, MA 02114, USA.
authors.forename: Hanna K
authors.initials: HK
authors.lastname: Gaggin
authors.forename: Quynh A
authors.initials: QA
authors.lastname: Truong
authors.forename: Shafiq U
authors.initials: SU
authors.lastname: Rehman
authors.forename: Asim A
authors.initials: AA
authors.lastname: Mohammed
authors.forename: Anju
authors.initials: A
authors.lastname: Bhardwaj
authors.forename: Kimberly A
authors.initials: KA
authors.lastname: Parks
authors.forename: Dorothy A
authors.initials: DA
authors.lastname: Sullivan
authors.forename: Annabel
authors.initials: A
authors.lastname: Chen-Tournoux
authors.forename: Stephanie A
authors.initials: SA
authors.lastname: Moore
authors.forename: A Mark
authors.initials: AM
authors.lastname: Richards
authors.forename: Richard W
authors.initials: RW
authors.lastname: Troughton
authors.forename: John G
authors.initials: JG
authors.lastname: Lainchbury
authors.forename: Rory B
authors.initials: RB
authors.lastname: Weiner
authors.forename: Aaron L
authors.initials: AL
authors.lastname: Baggish
authors.forename: Marc J
authors.initials: MJ
authors.lastname: Semigran
authors.forename: James L
authors.initials: JL
authors.lastname: Januzzi
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D004452:Echocardiography; D005260:Female; D005500:Follow-Up Studies; D006333:Heart Failure / Q000097:blood / Q000401:mortality / Q000628:therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood*; D010045:Outpatients; D010359:Patient Readmission / Q000639:trends*; D010446:Peptide Fragments / Q000097:blood*; D011379:Prognosis; D011446:Prospective Studies; D011498:Protein Precursors; D015996:Survival Rate / Q000639:trends; D014481:United States / Q000453:epidemiology; D016277:Ventricular Function, Left
chemical_list: D015415:Biomarkers; D010446:Peptide Fragments; D011498:Protein Precursors; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain