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............................................................................................................................................................................. Treatment with an ARNI may be considered in patients with HFmrEF.

7.3.6 Other drugs In the DIG trial,10 for those with HFmrEF in SR, there was a trend to fewer hospitalizations for HF in those assigned to digoxin, but no reduction in mortality and a trend to an excess of CV deaths. Therefore, there are insufficient data to recommend its use. There are also insufficient data on ivabradine in HFmrEF to draw any conclusions.

7.3.7 Devices While post hoc analyses of landmark CRT trials suggest that CRT may benefit patients with LVEF >35%, trials of CRT for HFmrEF were abandoned due to poor recruitment.250 There are no substantial trials of ICDs for primary prevention of ventricular arrhythmias for HFmrEF; trials conducted more than 20 years ago suggested no benefit from ICD implantation for secondary prevention of ventricular arrhythmias for HFmrEF. Therefore, there is insufficient evidence to advise CRT or ICD therapy in patients with HFmrEF. In HF patients with an LVEF >_40%, the implantation of an interatrial shunt device was found to be safe, and this device is subject to investigation in a larger study before any recommendation on their use in HFpEF or HFmrEF can be given.251

8 Heart failure with preserved

ejection fraction

8.1 The background to heart failure with

preserved ejection fraction This guideline acknowledges the historical changes in nomenclature and the lack of consensus on the optimal LVEF cut-off to define the group of patients with HF without overtly reduced EF. The term ‘preserved’ was originally proposed in the Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity (CHARM) Programme to refer to patients with an EF (>40%) that was not clearly ‘reduced’ or completely ‘normal’.252 While the current guidelines have designated patients with an LVEF 4149% as HFmrEF, we recognize that there will be debate about what constitutes ‘mildly reduced’ EF, what these EF cut-offs should be, and whether they should be different for men and women.14,253 The EACVI defines systolic dysfunction as being <52% for males and <54% for females.16 Whether patients with higher EFs and HF should be named HF with ‘normal’ EF has also been considered.14,254 However, given the known variability of echocardiographic measurements of LVEF, the difficulties in interpreting LVEF measured using different imaging modalities, and remaining controversies regarding the precise LVEF cut-off to define ‘normal’ , which may vary not only with sex but also with other factors such as age and ethnicity,255 this guideline has kept the nomenclature of HFpEF using an EF cut-off of 50%. Importantly, clinicians should be aware that LVEF is a continuous variable with a normal distribution in the general population, and the EF cut-offs used in definitions are therefore arbitrary. Moreover, while the LVEF cut-off to define ‘normal’ will likely be higher than 50%, the presence of a very high EF (e.g. above 6570%) should also prompt a search for pathology, such as cardiac amyloidosis (CA) or hypertrophic cardiomyopathy (HCM), where a ‘supra-normal’ EF may result from shrinkage of the LV end-diastolic volume (denominator of EF).256,257

8.2 Clinical characteristics of patients

with heart failure with preserved ejection fraction HFpEF differs from HFrEF and HFmrEF in that HFpEF patients are older and more often female. AF, CKD, and non-CV comorbidities are more common in patients with HFpEF than in those with HFrEF.258 There are numerous potential causes of HFpEF (Table 5). The pathophysiology of various HFpEF syndromes differs, and thus they require distinct therapies. Red flags for the potential presence of CA include low normal BP in patients with a history of hypertension, intolerance to beta-blockers or ACE-I, history of bilateral carpal tunnel syndrome, low voltage on ECG and echocardiographic features such as thickening of the septum, posterior wall, or RV wall, enlarged atria, a small pericardial effusion, or valve thickening [for more details see the section on CMP (section 14.2)]. Furthermore, it is important to exclude other conditions that might mimic the HFpEF syndrome (e.g. lung disease, anaemia, obesity, and deconditioning). For a more comprehensive overview on HFpEF, see the ESC/HFA position statement.259

8.3 The diagnosis of heart failure with

preserved ejection fraction The diagnosis of HFpEF remains challenging. Several diagnostic criteria have been proposed by societies and in clinical trials.260 These criteria vary widely in their sensitivities and specificities for diagnosing HFpEF. More recently, two score-based algorithms (H2FPEF and HFA-PEFF) have been proposed to aid the diagnosis.259,261 While the generalizability of the scores has been tested in various trial and observational cohorts, their diagnostic performance has varied.262269 Both scores assign a substantial proportion of suspected HFpEF patients as intermediate likelihood, wherein additional diagnostics are proposed. Thus, depending on which score is used, different patients will be referred for additional testing or allocated as having HFpEF. Furthermore, physicians may not have access to all the specialized tests recommended by the specific diagnostic algorithms. This limits the broad clinical applicability of the scores and demonstrates the ongoing diagnostic uncertainty in HFpEF.267 To facilitate broad clinical application, this guideline recommends a simplified pragmatic approach that distils the common major elements in prior diagnostic criteria and emphasizes the most frequently used variables widely available to clinicians. Some of these variables, in particular, LA size (LA volume index >32 mL/m2), mitral E velocity <90 cm/s, septal e0 velocity <9 cm/ s, E/e0 ratio >9 have been shown to be pivot points beyond which the risk of CV mortality is increased, underscoring their value.270 This recommendation is therefore consistent with the consensus document of the HFA, and does not represent a new algorithm or diagnostic score but rather a simplified approach. Physicians with access to expertise may refer to the full diagnostic approach recommended by the HFA.259 Downloaded from academic.oup.com/eurheartj/article/42/36/3599/6358045 by guest on 07 October 2026