How to diagnose heart failure with preserved ejection fraction: the HFA–PEFF diagnostic algorithm: a consensus recommendation from the Heart Failure Association (HFA) of the European Society of Cardiology (ESC)

Burkert Pieske^1,2,3,4*, Carsten Tschöpe^1,2,5, Rudolf A. de Boer⁶, Alan G. Fraser⁷, Stefan D. Anker^1,2,5,8, Erwan Donal⁹, Frank Edelmann^1,2, Michael Fu¹⁰, Marco Guazzi^11,12, Carolyn S.P. Lam^13,14, Patrizio Lancellotti¹⁵, Vojtech Melenovsky¹⁶, Daniel A. Morris¹, Eike Nagel ^17,18, Elisabeth Pieske-Kraigher¹, Piotr Ponikowski¹⁹, Scott D. Solomon²⁰, Ramachandran S. Vasan²¹, Frans H. Rutten ²², Adriaan A. Voors⁶, Frank Ruschitzka²³, Walter J. Paulus²⁴, Petar Seferovic²⁵, and Gerasimos Filippatos^26,27

¹Department of Internal Medicine and Cardiology, Charité - Universitätsmedizin Berlin, Campus Virchow Klinikum; ²German Center for Cardiovascular Research (DZHK), Berlin, Partner Site, Germany; ³Department of Internal Medicine and Cardiology, German Heart Institute, Berlin, Germany; ⁴Berlin Institute of Health (BIH), Germany; ⁵Berlin Institute of Health (BIH) Center for Regenerative Therapies (BCRT), Charite, Berlin, Germany; ⁶University Medical Centre Groningen, University of Groningen, Department of Cardiology, Groningen, the Netherlands; ⁷School of Medicine, Cardiff University, Cardiff, UK; ⁸Department of Cardiology and Pneumology, University Medicine Göttingen (UMG), Germany; ⁹Cardiology and CIC, IT1414, CHU de Rennes LTSI, Université Rennes-1, INSERM 1099, Rennes, France; ¹⁰Section of Cardiology, Department of Medicine, Sahlgrenska University Hosptal/Ostra, Göteborg, Sweden; ¹¹Department of Biomedical Sciences for Health, University of Milan, IRCCS, Milan, Italy; ¹²Department of Cardiology, IRCCS Policlinico, San Donato Milanese, Milan, Italy, ¹³National Heart Centre, Singapore & Duke-National University of Singapore; ¹⁴University Medical Centre Groningen, The Netherlands; ¹⁵Department of Cardiology, Heart Valve Clinic, University of Liège Hospital, GIGA Cardiovascular Sciences, CHU Sart Tilman, Liège, Belgium; ¹⁶Institute for Clinical and Experimental Medicine - IKEM, Prague, Czech Republic; ¹⁷Institute for Experimental and Translational Cardiovascular Imaging, University Hospital Frankfurt; ¹⁸German Centre for Cardiovascular Research (DZHK), Partner Site Frankfurt, Germany; ¹⁹Medical University, Clinical Military Hospital, Wroclaw, Poland; ²⁰Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA; ²¹Section of Preventive Medicine and Epidemiology and Cardiovascular Medicine, Department of Medicine, Boston University School of Medicine, Boston, MA, USA; ²²Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands; ²³University Heart Centre, University Hospital Zurich, Switzerland; ²⁴Department of Physiology and Amsterdam Cardiovascular Sciences, Amsterdam University Medical Center, The Netherlands; ²⁵University of Belgrade School of Medicine, Belgrade University Medical Center, Serbia; ²⁶Department of Cardiology, National and Kapodistrian University of Athens Medical School; University Hospital “Attikon”, Athens, Greece; and ²⁷University of Cyprus, School of Medicine, Nicosia, Cyprus

* Corresponding author. Tel: +49 30 450 553702, Fax: +49 30 450 7 553702, Email: [email protected]

Making a firm diagnosis of chronic heart failure with preserved ejection fraction (HFpEF) remains a challenge. We recommend a new stepwise diagnostic process, the ‘HFA–PEFF diagnostic algorithm’. Step 1 (P=Pre-test assessment) is typically performed in the ambulatory setting and includes assessment for HF symptoms and signs, typical clinical demographics (obesity, hypertension, diabetes mellitus, elderly, atrial fibrillation), and diagnostic laboratory tests, electrocardiogram, and echocardiography. In the absence of overt non-cardiac causes of breathlessness, HFpEF can be suspected if there is a normal left ventricular ejection fraction, no significant heart valve disease or cardiac ischaemia, and at least one typical risk factor. Elevated natriuretic peptides support, but normal levels do not exclude a diagnosis of HFpEF. The second step (E: Echocardiography and Natriuretic Peptide Score) requires comprehensive echocardiography and is typically performed by a cardiologist. Measures include mitral annular early diastolic velocity (e′), left ventricular (LV) filling pressure estimated using E/e′, left atrial volume index, LV mass index, LV relative wall thickness, tricuspid regurgitation velocity, LV global longitudinal systolic strain, and serum natriuretic peptide levels. Major (2 points) and Minor (1 point) criteria were defined from these measures. A score ≥5 points implies definite HFpEF; ≤1 point makes HFpEF unlikely. An intermediate score (2–4 points) implies diagnostic uncertainty, in which case Step 3 (F₁: Functional testing) is recommended with echocardiographic or invasive haemodynamic exercise stress tests. Step 4 (F₂: Final aetiology) is recommended to establish a possible specific cause of HFpEF or alternative explanations. Further research is needed for a better classification of HFpEF.

Keywords Heart failure • HFpEF • diagnosis • echocardiography • biomarkers • natriuretic peptides • exercise echocardiography

Figure 3 Step 2 (E): Echocardiographic and natriuretic peptide heart failure with preserved ejection fraction workup and scoring system (diagnostic workup).