Point-of-care B-type natriuretic peptide and portable echocardiography for assessment of patients with suspected heart failure in primary care: rationale and design of the three-part Handheld-BNP program and results of the training study
- 287 Downloads
Patients with suspected heart failure (HF) often present first to general practitioners (GPs). Timely and accurate HF diagnosis and reliable prognostic information have remained unmet goals in primary care, where patient evaluation often relies on clinical assessment only. The Handheld-BNP program investigates whether additional use of portable echocardiography (ECHO) and point-of-care determination of B-type natriuretic peptide (BNP) improves the accuracy of HF diagnosis and aids risk prediction in primary care.
Methods and results
A research network was established between 2 academic centers, 2 × 6 cardiologists, and 2 × 24 GPs inexperienced with ECHO and BNP. The Training Study investigates the feasibility of implementing GP use and interpretation of ECHO and BNP. After training, competence is assessed using multiple-choice testing (pass mark: > 80% correct diagnoses). In the cluster-randomized four-arm Screening Study, each GP passes in random order through four study arms: clinical assessment (CA), CA + BNP, CA + ECHO, and CA + ECHO + BNP. Cardiologists’ diagnoses serve as reference. Primary endpoint is the rate of correct GP diagnoses per study arm. In the Prognostic Follow-Up Study, patients are followed up centrally for 72 months. Forty-four GPs were successfully trained. With 225 ± 34 (75 ± 3) and 233 ± 28 (81 ± 7) min, respectively, total ECHO (BNP) training times were similar between centers I and II. Furthermore, training results did not differ between centers.
Standardized training of limited duration enabled GPs to use ECHO and BNP for HF diagnosis. The Handheld-BNP program will provide robust evaluation of the diagnostic effectiveness and prognostic value of these tools in primary care.
KeywordsPortable echocardiography B-type natriuretic peptide Heart failure Diagnosis Prognosis Primary care
The authors thank all general practitioners and cardiologists contributing to the Handheld-BNP program. General practitioners receive honoraria for patient enrolment and follow-up (€200 per randomized patient for enrolment visit, completion of case report form and delivery of biomaterials, and €20 per completed of follow-up case report form). Cardiologists receive honoraria for expert patient assessment (€200 per patient for baseline heart failure diagnosis and completion of case report form). The authors also thank patients willing to participate in the Handheld-BNP program. Patients are not compensated for study participation. The authors wish to especially thank Prof. Dr. Goetz Gelbrich (Institute for Clinical Epidemiology and Biometry, University of Würzburg) for statistical advice, Monika Hanke for supervision and quality control of data collection, and Robert Wenzl for expert graphical design of the figures. The authors also thank the clinical research teams at both study centers, and the study and data managers at the Clinical Trial Center Leipzig and at the Comprehensive Heart Failure Center, Würzburg. English language editing support was provided by Nicola Ryan, BSc, independent medical writer, supported by the University of Würzburg. The Handheld-BNP program is funded in the frame of the Competence Network Heart Failure by the Federal Ministry of Education and Research (BMBF), Germany (BMBF, Grants 01GI0205 and 01GI1202A). Equipment and test kits for BNP point-of-care testing are provided by Biosite Diagnostics GmbH, Gießerallee 31, 47877 Willich (now Alere Technologies GmbH, Löbstedter Str. 103–105 07749 Jena). Ultrasound equipment is provided by Philips Medizinsysteme Ultraschall, Röntgenstr. 24, 22335 Hamburg.
Compliance with ethical standards
Conflict of interest
Dr. Störk reported receiving grants from the Federal Ministry for Education and Research, Boehringer, and Santhera; grants and personal fees from Servier, Pfizer, Novartis, Roche Diagnostics, and Thermo Fisher/Brahms; and personal fees from AstraZeneca, Genzyme, Medtronic, and Bayer. Dr. Ertl reported receiving grants from the German Ministry of Education and Research; and grants and personal fees Novartis and Boehringer Ingelheim. Dr. Angermann reported receiving funding for the Handheld-BNP program in the frame of the Competence Network Heart Failure by the Federal Ministry of Education and Research (Grants 01GI0205 and 01GI1202A) and nonfinancial support of the Handheld-BNP program from Biosite Diagnostics (now Alere Technologies), Germany, and Philips Medizinsysteme Ultraschall, Germany. Outside the current project, Dr. Angermann reported grants, personal fees, nonfinancial support, and other from ResMed; grants, personal fees, and other from Novartis; grants and nonfinancial support from Thermo Fisher; grants and personal fees from Boehringer and Vifor; nonfinancial support from the University Hospital Würzburg and the Comprehensive Heart Failure Center Würzburg; and grant support from the German Ministry for Education and Research. All other authors state that they have no conflicts of interest to declare.
- 4.Benjamin EJ, Blaha MJ, Chiuve SE, Cushman M, Das SR, Deo R, de Ferranti SD, Floyd J, Fornage M, Gillespie C, Isasi CR, Jimenez MC, Jordan LC, Judd SE, Lackland D, Lichtman JH, Lisabeth L, Liu S, Longenecker CT, Mackey RH, Matsushita K, Mozaffarian D, Mussolino ME, Nasir K, Neumar RW, Palaniappan L, Pandey DK, Thiagarajan RR, Reeves MJ, Ritchey M, Rodriguez CJ, Roth GA, Rosamond WD, Sasson C, Towfighi A, Tsao CW, Turner MB, Virani SS, Voeks JH, Willey JZ, Wilkins JT, Wu JH, Alger HM, Wong SS, Muntner P, American Heart Association Statistics C, Stroke Statistics S (2017) Heart disease and stroke statistics-2017 update: a report from the American Heart Association. Circulation 135:e146–e603CrossRefGoogle Scholar
- 5.Hobbs FD, Kenkre JE, Roalfe AK, Davis RC, Hare R, Davies MK (2002) Impact of heart failure and left ventricular systolic dysfunction on quality of life: a cross-sectional study comparing common chronic cardiac and medical disorders and a representative adult population. Eur Heart J 23:1867–1876CrossRefPubMedGoogle Scholar
- 12.Wright SP, Doughty RN, Pearl A, Gamble GD, Whalley GA, Walsh HJ, Gordon G, Bagg W, Oxenham H, Yandle T, Richards M, Sharpe N (2003) Plasma amino-terminal pro-brain natriuretic peptide and accuracy of heart-failure diagnosis in primary care: a randomized, controlled trial. J Am Coll Cardiol 42:1793–1800CrossRefPubMedGoogle Scholar
- 16.Ponikowski P, Voors AA, Anker SD, Bueno H, Cleland JG, Coats AJ, Falk V, Gonzalez-Juanatey JR, Harjola VP, Jankowska EA, Jessup M, Linde C, Nihoyannopoulos P, Parissis JT, Pieske B, Riley JP, Rosano GM, Ruilope LM, Ruschitzka F, Rutten FH, van der Meer P, Authors/Task Force M (2016) 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC)Developed with the special contribution of the Heart Failure Association (HFA) of the ESC. Eur Heart J 37:2129–2200CrossRefPubMedGoogle Scholar
- 17.Wierzchowiecki M, Poprawski K, Nowicka A, Kandziora M, Piatkowska A (2005) Knowledge of primary care physicians, cardiologists from cardiology clinics, internal and cardiology department physicians about chronic heart failure diagnosis and treatment. Pol Merkur Lekarski 18:210–215PubMedGoogle Scholar
- 20.Pfeffer MA, Braunwald E, Moye LA, Basta L, Brown EJ Jr, Cuddy TE, Davis BR, Geltman EM, Goldman S, Flaker GC et al (1992) Effect of captopril on mortality and morbidity in patients with left ventricular dysfunction after myocardial infarction. Results of the survival and ventricular enlargement trial. The SAVE Investigators. N Engl J Med 327:669–677CrossRefPubMedGoogle Scholar
- 21.McMurray JJ, Adamopoulos S, Anker SD, Auricchio A, Bohm M, Dickstein K, Falk V, Filippatos G, Fonseca C, Gomez-Sanchez MA, Jaarsma T, Kober L, Lip GY, Maggioni AP, Parkhomenko A, Pieske BM, Popescu BA, Ronnevik PK, Rutten FH, Schwitter J, Seferovic P, Stepinska J, Trindade PT, Voors AA, Zannad F, Zeiher A, Guidelines ESCCfP (2012) ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2012: the task force for the diagnosis and treatment of acute and chronic heart failure 2012 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association (HFA) of the ESC. Eur Heart J 33:1787–1847CrossRefPubMedGoogle Scholar
- 22.Dickstein K, Cohen-Solal A, Filippatos G, McMurray JJ, Ponikowski P, Poole-Wilson PA, Stromberg A, van Veldhuisen DJ, Atar D, Hoes AW, Keren A, Mebazaa A, Nieminen M, Priori SG, Swedberg K, Guidelines ESCCfP (2008) ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2008: the task force for the diagnosis and treatment of acute and chronic heart failure 2008 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association of the ESC (HFA) and endorsed by the European Society of Intensive Care Medicine (ESICM). Eur Heart J 29:2388–2442CrossRefPubMedGoogle Scholar
- 23.Maisel AS, Krishnaswamy P, Nowak RM, McCord J, Hollander JE, Duc P, Omland T, Storrow AB, Abraham WT, Wu AH, Clopton P, Steg PG, Westheim A, Knudsen CW, Perez A, Kazanegra R, Herrmann HC, McCullough PA, Breathing Not Properly Multinational Study I (2002) Rapid measurement of B-type natriuretic peptide in the emergency diagnosis of heart failure. N Engl J Med 347:161–167CrossRefPubMedGoogle Scholar
- 25.McCullough PA, Nowak RM, McCord J, Hollander JE, Herrmann HC, Steg PG, Duc P, Westheim A, Omland T, Knudsen CW, Storrow AB, Abraham WT, Lamba S, Wu AH, Perez A, Clopton P, Krishnaswamy P, Kazanegra R, Maisel AS (2002) B-type natriuretic peptide and clinical judgment in emergency diagnosis of heart failure: analysis from breathing not properly (BNP) Multinational Study. Circulation 106:416–422CrossRefPubMedGoogle Scholar
- 26.Burri E, Hochholzer K, Arenja N, Martin-Braschler H, Kaestner L, Gekeler H, Hatziisaak T, Buttiker M, Fraulin A, Potocki M, Breidthardt T, Reichlin T, Socrates T, Twerenbold R, Mueller C (2012) B-type natriuretic peptide in the evaluation and management of dyspnoea in primary care. J Intern Med 272:504–513CrossRefPubMedGoogle Scholar
- 27.Zaphiriou A, Robb S, Murray-Thomas T, Mendez G, Fox K, McDonagh T, Hardman SM, Dargie HJ, Cowie MR (2005) The diagnostic accuracy of plasma BNP and NTproBNP in patients referred from primary care with suspected heart failure: results of the UK natriuretic peptide study. Eur J Heart Fail 7:537–541CrossRefPubMedGoogle Scholar
- 29.Fuat A, Murphy JJ, Hungin AP, Curry J, Mehrzad AA, Hetherington A, Johnston JI, Smellie WS, Duffy V, Cawley P (2006) The diagnostic accuracy and utility of a B-type natriuretic peptide test in a community population of patients with suspected heart failure. Br J Gen Pract 56:327–333PubMedPubMedCentralGoogle Scholar
- 34.Kelder JC, Cramer MJ, van Wijngaarden J, van Tooren R, Mosterd A, Moons KG, Lammers JW, Cowie MR, Grobbee DE, Hoes AW (2011) The diagnostic value of physical examination and additional testing in primary care patients with suspected heart failure. Circulation 124:2865–2873CrossRefPubMedGoogle Scholar
- 42.Tait L, Roalfe AK, Mant J, Cowie MR, Deeks JJ, Iles R, Barton PM, Taylor CJ, Derit M, Hobbs FD (2012) The REFER (REFer for EchocaRdiogram) protocol: a prospective validation of a clinical decision rule, NT-proBNP, or their combination, in the diagnosis of heart failure in primary care. Rationale and design. BMC Cardiovasc Disord 12:97CrossRefPubMedPubMedCentralGoogle Scholar
- 44.Maisel A, Mueller C, Adams K Jr, Anker SD, Aspromonte N, Cleland JG, Cohen-Solal A, Dahlstrom U, DeMaria A, Di Somma S, Filippatos GS, Fonarow GC, Jourdain P, Komajda M, Liu PP, McDonagh T, McDonald K, Mebazaa A, Nieminen MS, Peacock WF, Tubaro M, Valle R, Vanderhyden M, Yancy CW, Zannad F, Braunwald E (2008) State of the art: using natriuretic peptide levels in clinical practice. Eur J Heart Fail 10:824–839CrossRefPubMedGoogle Scholar
- 47.Excellence NIoHaC Chronic heart failure in adults: management. CG108. https://www.nice.org.uk/guidance/cg108/chapter/1-Guidance-diagnosing-heart-failure. Accessed 29 Sept 2017
- 55.Fedson S, Neithardt G, Thomas P, Lickerman A, Radzienda M, DeCara JM, Lang RM, Spencer KT (2003) Unsuspected clinically important findings detected with a small portable ultrasound device in patients admitted to a general medicine service. J Am Soc Echocardiogr 16:901–905CrossRefPubMedGoogle Scholar
- 57.Evangelista A, Galuppo V, Mendez J, Evangelista L, Arpal L, Rubio C, Vergara M, Liceran M, Lopez F, Sales C, Miralles V, Galinsoga A, Perez J, Arteaga M, Salvador B, Lopez C, Garcia-Dorado D (2016) Hand-held cardiac ultrasound screening performed by family doctors with remote expert support interpretation. Heart 102:376–382CrossRefPubMedGoogle Scholar
- 60.Seward JB, Douglas PS, Erbel R, Kerber RE, Kronzon I, Rakowski H, Sahn LD, Sisk EJ, Tajik AJ, Wann S (2002) Hand-carried cardiac ultrasound (HCU) device: recommendations regarding new technology. A report from the Echocardiography Task Force on New Technology of the Nomenclature and Standards Committee of the American Society of Echocardiography. J Am Soc Echocardiogr 15:369–373CrossRefPubMedGoogle Scholar
- 62.Mehrhof F, Loffler M, Gelbrich G, Ozcelik C, Posch M, Hense HW, Keil U, Scheffold T, Schunkert H, Angermann C, Ertl G, Jahns R, Pieske B, Wachter R, Edelmann F, Wollert KC, Maisch B, Pankuweit S, Erbel R, Neumann T, Herzog W, Katus H, Muller-Tasch T, Zugck C, Dungen HD, Regitz-Zagrosek V, Lehmkuhl E, Stork S, Siebert U, Wasem J, Neumann A, Gohler A, Anker SD, Kohler F, Mockel M, Osterziel KJ, Dietz R, Rauchhaus M, Competence Network Heart F (2010) A network against failing hearts—introducing the German “Competence Network Heart Failure”. Int J Cardiol 145:135–138CrossRefPubMedGoogle Scholar
- 68.Ware JE (1996) The SF-36 health survey. In: Spilker B (ed) Quality of life and pharmacoeconomics in clinical trials. Raven, Philadelphia, pp 337–346Google Scholar
- 73.Roberts E, Ludman AJ, Dworzynski K, Al-Mohammad A, Cowie MR, McMurray JJ, Mant J, Nice Guideline Development Group for Acute Heart Failure (2015) The diagnostic accuracy of the natriuretic peptides in heart failure: systematic review and diagnostic meta-analysis in the acute care setting. BMJ 350:h910CrossRefPubMedPubMedCentralGoogle Scholar