A Point-of-Care Measurement of NT-proBNP for Heart Failure Patients

Heart Failure (HF) diagnosis, subsequent admissions, and possible readmissions present challenges for health systems worldwide. An increasing number of patients within an ageing population are surviving cardiac conditions which can leave them with residual heart function impairment. Follow-up visits of either confirmed HF sufferers or HF high-risk patients could be reduced through the implementation of Point-of-Care (PoC) measurement of N-terminal pro-B-type natriuretic peptide (NT-proBNP), an inactive signal portion of the active hormone BNP that is released in response to cardiac wall stretch. Serial measurements of NT-proBNP concentration may serve to indicate progress/deterioration of HF sufferers which in turn indicates the quality of the interventions designed to treat HF. We present an integrated PoC solution that involves the user-friendly, low volume sampling of blood directly into a single-use sampling key with an integral NT-proBNP biomarker detection strip operating on a lateral flow immunoassay principle. When inserted into a corresponding portable electronic reader it forms an integrated detection and measurement platform that wirelessly communicates measurements (Wi-Fi) for cloud-based reporting, trending and data analysis. The system provides a practical, inexpensive support tool for HF management by informing those involved in clinical decision-making with necessary biomarker data. The PoC NT-proBNP measurement compares well against alternative technologies based on image analysis.

[1]  D. Altman,et al.  STATISTICAL METHODS FOR ASSESSING AGREEMENT BETWEEN TWO METHODS OF CLINICAL MEASUREMENT , 1986, The Lancet.

[2]  Andreas Pahle,et al.  Diagnosing heart failure with NT-proBNP point-of-care testing: lower costs and better outcomes. A decision analytic study , 2018, BJGP open.

[3]  Suhas S. Joshi,et al.  Passive blood plasma separation at the microscale: a review of design principles and microdevices , 2015 .

[4]  Vangelis Sakkalis,et al.  Congestive Heart Failure Risk Assessment Monitoring through Internet of things and mobile Personal Health Systems , 2018, 2018 40th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC).

[5]  Amin M. Abbosh,et al.  Microwave System for the Early Stage Detection of Congestive Heart Failure , 2014, IEEE Access.

[6]  Michael Daniele,et al.  Quantum dot enabled lateral flow immunoassay for detection of cardiac biomarker NT-proBNP , 2018, Sensing and Bio-Sensing Research.

[7]  Francesco Portaluppi,et al.  Elevated NT-proBNP levels should be interpreted in elderly patients presenting with dyspnea. , 2011, European journal of internal medicine.

[8]  M.H. Baljon,et al.  Evaluating connectivity for a heart failure database , 2002, Computers in Cardiology.

[9]  J. Abramowitz,et al.  Fear of needles and vasovagal reactions among phlebotomy patients. , 2006, Journal of anxiety disorders.

[10]  I. Sarangadharan,et al.  Rapid detection of NT-proBNP from whole blood using FET based biosensors for homecare , 2019, Sensors and Actuators B: Chemical.

[11]  Alan S Maisel,et al.  Effect of nesiritide in combination with standard therapy on serum concentrations of natriuretic peptides in patients admitted for decompensated congestive heart failure. , 2005, American heart journal.

[12]  Ian Richards,et al.  Managing Heart Failure at Home With Point-of-Care Diagnostics , 2017, IEEE Journal of Translational Engineering in Health and Medicine.

[13]  Biykem Bozkurt,et al.  2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on practice guidelines. , 2013, Circulation.

[14]  F. Brochard-Wyart,et al.  Droplets: Capillarity and Wetting , 1999 .

[15]  Jongwon Park,et al.  An Optimized Colorimetric Readout Method for Lateral Flow Immunoassays , 2018, Sensors.

[16]  Ana I. Barbosa,et al.  Towards One-Step Quantitation of Prostate-Specific Antigen (PSA) in Microfluidic Devices: Feasibility of Optical Detection with Nanoparticle Labels , 2017, BioNanoScience.

[17]  A. G. Semenov,et al.  Analytical Issues with Natriuretic Peptides – has this been Overly Simplified? , 2016, EJIFCC.

[18]  Shalini Prasad,et al.  Nanosensor electrical immunoassay for quantitative detection of NT-pro brain natriuretic peptide. , 2013, Future cardiology.

[19]  K. Nakao,et al.  Rapid transcriptional activation and early mRNA turnover of brain natriuretic peptide in cardiocyte hypertrophy. Evidence for brain natriuretic peptide as an "emergency" cardiac hormone against ventricular overload. , 1995, The Journal of clinical investigation.

[20]  Fred S Apple,et al.  Immunodetection of glycosylated NT-proBNP circulating in human blood. , 2008, Clinical chemistry.

[21]  Juerg Schwitter,et al.  ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2012 , 2010, European journal of heart failure.

[22]  Mario Plebani,et al.  Recommendations for the use of natriuretic peptides in acute cardiac care: a position statement from the Study Group on Biomarkers in Cardiology of the ESC Working Group on Acute Cardiac Care. , 2012, European heart journal.

[23]  Barry Greenberg,et al.  Primary results of the HABIT Trial (heart failure assessment with BNP in the home). , 2013, Journal of the American College of Cardiology.

[24]  W Frank Peacock,et al.  State of the art: Using natriuretic peptide levels in clinical practice , 2008, European journal of heart failure.

[25]  Yifan Li,et al.  Multi-Frequency Components Entropy as Novel Heart Rate Variability Indices in Congestive Heart Failure Assessment , 2019, IEEE Access.

[26]  Juan Cinca,et al.  Usefulness of clinical and NT-proBNP monitoring for prognostic guidance in destabilized heart failure outpatients. , 2008, European heart journal.

[27]  J. Januzzi,et al.  Natriuretic peptide testing in heart failure. , 2011, Circulation.

[28]  Xiaopeng Wei,et al.  Predicting the Risk of Heart Failure With EHR Sequential Data Modeling , 2018, IEEE Access.

[29]  A StJohn,et al.  Existing and Emerging Technologies for Point-of-Care Testing. , 2014 .

[30]  Li Nan,et al.  Brain natriuretic peptide and optimal management of heart failure , 2005 .

[31]  E. Hrncír,et al.  Surface tension of blood. , 1997, Physiological research.

[32]  C. Schneider,et al.  ESC guidelines for the diagnosis and treatment of acute and chronic heart failure 2008: application of natriuretic peptides. , 2008, European heart journal.

[33]  Martin Gjoreski,et al.  Machine Learning and End-to-End Deep Learning for the Detection of Chronic Heart Failure From Heart Sounds , 2020, IEEE Access.

[34]  Shihui Fu,et al.  Brain Natriuretic Peptide and Its Biochemical, Analytical, and Clinical Issues in Heart Failure: A Narrative Review , 2018, Front. Physiol..

[35]  W. Jian-an,et al.  Brain natriuretic peptide and optimal management of heart failure , 2005, Journal of Zhejiang University Science B.

[36]  Gianluigi Savarese,et al.  Global Public Health Burden of Heart Failure. , 2016, Cardiac failure review.

[37]  Heather R Peck,et al.  A survey of apparent blood volumes and sample geometries among filter paper bloodspot samples submitted for lead screening. , 2009, Clinica chimica acta; international journal of clinical chemistry.

[38]  E. Bahadır,et al.  Lateral flow assays: Principles, designs and labels , 2016 .

[39]  Eric S. Nordman,et al.  A Low-Cost, High-Performance System for Fluorescence Lateral Flow Assays , 2013, Biosensors.

[40]  Michael J. Pencina,et al.  Serial Measurements of N-Terminal Pro-Brain Natriuretic Peptide in Patients with Coronary Heart Disease , 2015, PloS one.

[41]  Hengyi Xu,et al.  Development of an immunochromatographic assay for rapid and quantitative detection of clenbuterol in swine urine , 2013 .

[42]  Kevin W Eliceiri,et al.  NIH Image to ImageJ: 25 years of image analysis , 2012, Nature Methods.

[43]  Andrew St John,et al.  Existing and Emerging Technologies for Point-of-Care Testing. , 2014, The Clinical biochemist. Reviews.

[44]  Gianni Tognoni,et al.  Prognostic value of changes in N-terminal pro-brain natriuretic peptide in Val-HeFT (Valsartan Heart Failure Trial). , 2008, Journal of the American College of Cardiology.

[45]  Ruo Yuan,et al.  An ultrasensitive electrochemiluminescence immunosensor for NT-proBNP based on self-catalyzed luminescence emitter coupled with PdCu@carbon nanohorn hybrid. , 2017, Biosensors & bioelectronics.

[46]  Claudio Passino,et al.  Comparison of the diagnostic accuracy of brain natriuretic peptide (BNP) and the N-terminal part of the propeptide of BNP immunoassays in chronic and acute heart failure: a systematic review. , 2007, Clinical chemistry.

[47]  Anders Larsson,et al.  Specificity of B-type natriuretic peptide assays: Knockin’ on the assay door , 2017 .

[48]  C. V. Van Peteghem,et al.  Preliminary evaluation of a lateral flow immunoassay device for screening urine samples for the presence of sulphamethazine. , 2003, Journal of immunological methods.

[49]  Xuena Zhu,et al.  Paper-based Immunosensor for Oxidative DNA Damage Biomarker Detection , 2013, 2013 29th Southern Biomedical Engineering Conference.

[50]  Taisun Kim,et al.  Ultra-Sensitive NT-proBNP Quantification for Early Detection of Risk Factors Leading to Heart Failure , 2017, Sensors.

[51]  K. M. Koczula,et al.  Lateral flow assays , 2016, Essays in biochemistry.

[52]  A. G. Semenov,et al.  Standardization of BNP and NT-proBNP Immunoassays in Light of the Diverse and Complex Nature of Circulating BNP-Related Peptides. , 2018, Advances in clinical chemistry.

[53]  C. Hamm,et al.  B-type natriuretic peptide and N-terminal pro-B-type natriuretic peptide - Diagnostic role in stable coronary artery disease. , 2006, Experimental and clinical cardiology.

[54]  Torben Breindahl,et al.  NT-proBNP on Cobas h 232 in point-of-care testing: Performance in the primary health care versus in the hospital laboratory , 2015, Scandinavian journal of clinical and laboratory investigation.

[55]  Paul Yager,et al.  CO2 laser cutting and ablative etching for the fabrication of paper-based devices , 2013 .