. . . . . . . . . . . . . . . . . . Value of combined cardiopulmonary and echocardiography stress test to characterize the haemodynamic and metabolic responses of patients with heart failure and mid-range ejection fraction Nicola Riccardo Pugliese 1,2 *, Iacopo Fabiani 1,2 , Claudia Santini 2 , Ilaria Rovai 2 , Roberto Pedrinelli 2 , Andrea Natali 3 , and Frank L. Dini 2 1 Department of Surgical, Medical, Molecular Pathology and Critical Area, University of Pisa, Via Paradisa, 2, 56124 Pisa, Italy; 2 Cardiac, Thoracic and Vascular Department, University of Pisa, Via Paradisa, 2, 56124 Pisa, Italy; and 3 Department of Clinical and Experimental Medicine, University of Pisa, Via Paradisa, 2, 56124 Pisa, Italy Received 5 December 2018; editorial decision 18 January 2019; accepted 21 January 2019; online publish-ahead-of-print 11 February 2019 Aims To characterize heart failure (HF) with mid-range ejection fraction (HFmrEF), combining cardiopulmonary exercise test, and exercise stress echocardiography. ................................................................................................................................................................................................... Methods and results We studied 169 consecutive subjects (age 62.3 ± 11 years; 74% male): 30 healthy controls, 45 patients with HF and preserved EF (HFpEF), 40 HFmrEF, and 54 with HF and reduced EF (HFrEF). Left ventricular (LV) stroke volume (SV), EF, elastance, global longitudinal strain, E/E’, oxygen consumption (VO 2 ), and arterial-venous oxygen content difference (AVO 2 diff) were measured in all exercise stages. HFmrEF revealed baseline features intermediate be- tween HFrEF and HFpEF, except for B-type natriuretic peptide levels, which was similar to HFpEF and significantly lower than HFrEF. Peak VO 2 was not significantly different between HF groups. HFrEF exhibited a significantly lower peak SV as compared to either HFpEF or HFmrEF (74.3 ± 21.8 mL vs. 88.0 ± 17.4 mL and 96.5 ± 25.1 mL; P < 0.01), whereas peak heart rate was not significantly different between HF groups. A significantly reduced AVO 2 diff at peak exercise was apparent in HFpEF and HFmrEF (15.2 ± 3.3 mL/dL and 13.3 ± 4.2 mL/dL) vs. HFrEF (17.±6.6 mL/dL; P < 0.01), whereas no significant difference was reported between HFpEF and HFmrEF. Multivariate analysis in the overall population and all groups revealed peak parameters as independent predictors of peak VO 2 (R 2 = 0.90, P < 0.0001); AVO 2 diff showed the largest standardized regression coefficient. ................................................................................................................................................................................................... Conclusion In HFpEF and HFmrEF, effort intolerance is predominantly due to peripheral factors (AVO 2 diff), whereas in HFrEF peak VO 2 is restricted by low increases in SV. Individual therapy according to which component of VO 2 is more impaired is advisable.                                                                                                                                                                                                                     Keywords heart failure • ejection fraction • cardiopulmonary exercise test • exercise stress echocardiography Introduction Heart failure (HF) is a complex clinical syndrome, characterized by different aetiologies and a broad spectrum of left ventricular (LV) functional abnormalities. The 2016 European HF guidelines have re- cently suggested a more sophisticated ejection fraction (EF)-based HF classification: reduced EF (<40%; HFrEF), mid-range EF [40–49%; HF with mid-range EF (HFmrEF)], and preserved EF [>_50%; HF and reduced EF (HFpEF)]. 1,2 At present, there is no evident defining syn- drome recognized for HmrEF: it resembles both HFrEF, concerning the previous history of coronary artery disease, and HFpEF concern- ing many baseline characteristics, including older age, female sex, car- * Corresponding author. Tel: þ39 (05) 099 5315; Fax: þ39 (05) 099 5316. E-mail: n.r.pugliese88@gmail.com Published on behalf of the European Society of Cardiology. All rights reserved. VC The Author(s) 2019. For permissions, please email: journals.permissions@oup.com. European Heart Journal - Cardiovascular Imaging (2019) 20, 828–836 doi:10.1093/ehjci/jez014 Downloaded from https://academic.oup.com/ehjcimaging/article/20/7/828/5315639 by guest on 18 February 2023