Cardiopulmonary exercise testing (CPET), particularly peak oxygen uptake (pVO2), may be a useful tool to predict cardiovascular death risk in patients with reduced heart failure with midrange ejection fraction (HFmrEF), according to a study published in the Journal of Cardiac Failure.

The prognostic assessment of HFmrEF remains unclear due the relatively recent introduction and the heterogeneity of profiles. In this study, researchers sought to characterize and compare a specific HFmrEF subset (ie, patients who recovered from HFmrEF [rec-HFmrEF]) to determine the prognostic value of CPET.

The researchers retrospectively analyzed data of outpatients from the Metabolic Exercise combined with Cardiac and Kidney Indexes (MECKI) database from 27 Italian HF centers (n=4535 with HF with reduced EF [HFrEF]; n=1176 rec-HFmrEF).Patients included had HF signs/and or symptoms, were on stable clinical conditions with unchanged medications for at least 3 months, had no major cardiovascular treatment or intervention scheduled, and capability to perform a maximal, symptom-limited CPET. The study’s endpoint was cardiovascular death at 5 years. The study’s median follow-up was 1343 days (25th–75th range, 627-2,403 days).

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Cardiovascular death occurred in 552 patients with HFrEF (12.2% event rate) vs 61 patients with rec-HFmrEF (5.2% event rate). In addition to the variables accounted for in the MECKI score, age was found to be independently associated with cardiovascular death (C-index for the entire model 0.744) in the HFrEF group, in a multivariate Cox analysis. In the rec-HFmrEF group, only 2 variables — age and pVO2, expressed as percentage of the maximum predicted — remained significantly associated to the outcome (C-index for the entire model 0.745). When focusing on the rec-HFmrEF group, the receiver operating characteristic curve analysis showed that the best pVO2 threshold was equal to 55% (sensitivity 65%; specificity 62%; area under the curve [AUC], 69%) whereas the best minute ventilation/carbon dioxide production slope cut-off value was 31 (sensitivity 56%; specificity 73%; AUC, 67%), representing the most accurate cutoff values in the outcome prediction.

Limitations of the study include the facts that the prognostic impact of several variables was examined at a single time point, that the lack of significance of some variables may be driven much more by the differences in sample size between groups than by an effective lack of clinical relationship in the rec-HFmrEF group, and due to the design of the MECKI score dataset, the lack of data with respect to the timeline between disease onset and LVEF recovery did not allow for the speculation of the possible impact of the medical treatment length on the HF category interchange.

“Further interventional and prospective studies are needed to confirm and, possibly, to translate our results into the daily HFmrEF clinical management,” concluded the study authors.


Magri D, Massimo P, Corra U, Gallo G, Maruotti A, Vignati C, et al. Cardiovascular death risk in recovered mid-range ejection fraction heart failure: Insights from cardiopulmonary exercise test. J Card Fail. 2020 May 16; S1071-9164(20)30031-2.