LAUSR

The H2FPEF and HFA-PEFF scores have recently been proposed to solve the clinical dilemma of diagnosing heart failure with preserved ejection fraction (HFpEF).1,2 The H2FPEF score includes four clinical [age, body mass index (BMI), atrial fibrillation (AF) and hypertension] and two echocardiographic items (E/e′ and right ventricular pressure). The HFA-PEFF score contains minor and major criteria within three domains: functional (E/e′, e′, tricuspid regurgitation velocity, global longitudinal strain), morphological (left atrial volume index and parameters reflecting left ventricular hypertrophy) and natriuretic peptides. A H2FPEF score ≥6 or a HFA-PEFF ≥5 points is considered diagnostic of HFpEF. A H2FPEF score of 2–5 or a HFA-PEFF of 2–4 points classifies patients as having an intermediate likelihood of HFpEF wherein invasive haemodynamic evaluation — preferably with exercise — or exercise echocardiography is proposed by the authors.1,2 Two studies validated each score separately in Western populations.3,4 Recently in this Journal, the two scores showed rather comparable diagnostic performance in an Asian case-control cohort, although lower than in the cited Western populations.5 Both scores were predictive of adverse outcome in a Western population, although the risk prediction was very discordant between the two.6 We hypothesized that the two scores classify a significant proportion of suspected HFpEF patients differently in terms of likelihood categories. We calculated the absolute H2FPEF and HFA-PEFF scores1,2 and their likelihood categories (Figure 1) in 363 consecutive patients with suspected HFpEF. In summary, all patients from our outpatient HFpEF clinic (2015–2019) with a left ventricular ejection fraction (LVEF) of ≥50% were included prospectively and underwent a comprehensive one-day diagnostic work-up including echocardiography, blood, exercise, and pulmonary function testing, sleep apnoea screening and Holter.4 Exclusion criteria were: previously reduced LVEF <50%, familiar/genetic hypertrophic cardiomyopathy, significant valvular or congenital disease, constrictive pericarditis, or heart transplantation. The final HFpEF diagnosis was expert adjudicated (consented by ≥2 heart failure cardiologists: V.P.M.v.E., H.P.B.L.R., C.K., N.U.L.), considering all baseline investigations, previous heart failure hospitalization(s), congestion with positive response to diuretic therapy and previous natriuretic peptide levels (e.g. before diuretic therapy). In case of clinical uncertainty, invasive haemodynamic evaluation was performed (n = 79; 21.8%). The area under the receiver operating characteristic curve (AUC) was calculated for each score and compared using DeLong test. Sensitivity, specificity, negative and positive predictive value were calculated for each score (H2FPEF≥6 and HFA-PEFF ≥5). Differential patient classification by the two scores in terms of likelihood categories was visualized by a Sankey diagram and tested by Wilcoxon signed-rank test. Imputation of missing values in items of the scores was described previously4; sensitivity analysis excluded patients with any imputed value (n = 68; 19%). Patients diagnosed with HFpEF (n = 300, 83%) were older (76± 8 vs. 67± 11 years, P< 0.001) and more often suffered from AF (56% vs. 21%, P< 0.001), but did not differ in terms of sex (67% vs. 63% female, P = 0.66), arterial hypertension (86% vs. 76%, P = 0.08), or diabetes mellitus (33% vs. 24%, P = 0.18) vs. non-HFpEF patients (online supplementary Table S1). The final diagnosis in the non-HFpEF group was mostly pulmonary disease (n = 29; 46%), including obstructive sleep apnoea syndrome (n = 12) and obstructive, restrictive, interstitial and vascular pulmonary disease. Other diagnoses were obesity (n = 5), AF (n = 4), coronary artery disease (n = 3), deconditioning (n = 3), or a combination of factors (n = 6). Finally, five patients were asymptomatic hypertensive controls and five had a transient cause of dyspnoea (e.g. anaemia, infection). Diagnostic accuracy in terms of AUC was good for both scores, albeit sensitivity and negative predictive value were limited. This was offset by a good specificity and positive predictive value (Table 1). In 41% of our cohort (n = 145; 42% when excluding imputed data), patients were classified into different likelihood categories, depending on the score used (P< 0.001, Figure 1). Patients with an assigned H2FPEF category higher than their assigned HFA-PEFF category (H2FPEF>HFA-PEFF) most often suffered from AF (82.0% vs. 14.0% and 61%,