Left ventricular ejection fraction digit bias and reclassification of heart failure with mildly reduced vs reduced ejection fraction based on the 2021 definition and classification of heart failure.

AIMS: Aims were to evaluate (1) reclassification of patients from heart failure with mildly reduced (HFmrEF) to reduced (HFrEF) ejection fraction when an EF = 40% was considered as HFrEF, (2) role of EF digit bias, ie, EF reporting favouring 5% increments; (3) outcomes in relation to missing and biased EF reports, in a large multinational HF registry. METHODS AND RESULTS: Of 25,154 patients in the European Society of Cardiology (ESC) HF Long-Term registry, 17% had missing EF and of those with available EF, 24% had HFpEF (EF≥50%), 21% HFmrEF (40%-49%) and 55% HFrEF (<40%) according to the 2016 ESC guidelines´ classification. EF was "exactly" 40% in 7%, leading to reclassifying 34% of the HFmrEF population defined as EF = 40% to 49% to HFrEF when applying the 2021 ESC Guidelines classification (14% had HFmrEF as EF = 41% to 49% and 62% had HFrEF as EF≤40%). EF was reported as a value ending with 0 or 5 in ∼37% of the population. Such potential digit bias was associated with more missing values for other characteristics and higher risk of all-cause death and HF hospitalization. Patients with missing EF had higher risk of all-cause and CV mortality, and HF hospitalization compared to those with recorded EF. CONCLUSIONS: Many patients had reported EF = 40%. This led to substantial reclassification of EF from old HFmrEF (40%-49%) to new HFrEF (≤40%). There was considerable digit bias in EF reporting and missing EF reporting, which appeared to occur not at random and may reflect less rigorous overall care and worse outcomes.

Prevention and Rehabilitation After Heart Transplantation: A Clinical Consensus Statement of the European Association of Preventive Cardiology, Heart Failure Association of the ESC, and the European Cardio Thoracic Transplant Association, a Section of ESOT.

Little is known either about either physical activity patterns, or other lifestyle-related prevention measures in heart transplantation (HTx) recipients. The history of HTx started more than 50 years ago but there are still no guidelines or position papers highlighting the features of prevention and rehabilitation after HTx. The aims of this scientific statement are (i) to explain the importance of prevention and rehabilitation after HTx, and (ii) to promote the factors (modifiable/non-modifiable) that should be addressed after HTx to improve patients' physical capacity, quality of life and survival. All HTx team members have their role to play in the care of these patients and multidisciplinary prevention and rehabilitation programmes designed for transplant recipients. HTx recipients are clearly not healthy disease-free subjects yet they also significantly differ from heart failure patients or those who are supported with mechanical circulatory support. Therefore, prevention and rehabilitation after HTx both need to be specifically tailored to this patient population and be multidisciplinary in nature. Prevention and rehabilitation programmes should be initiated early after HTx and continued during the entire post-transplant journey. This clinical consensus statement focuses on the importance and the characteristics of prevention and rehabilitation designed for HTx recipients.

ß-Blockers and Erectile Dysfunction in Heart Failure. Between Myth and Reality.

Erectile dysfunction (ED) is a major concern in heart failure (HF) due its high prevalence as well as its negative impact on the quality of life, this condition being usually unrecognized and thus untreated. A number of possible causes might contribute to the above mentioned tight association, i.e., shared risk factors, comorbidities and several physiologic HF abnormalities such as impaired exercise tolerance, psychogenic factors and neurohumoral, metabolic and vascular changes. Medications have been blamed for playing also a pivotal role in the ED occurrence and, particularly, the ß -blockers. Remarkably, the underlying mechanisms have not been fully identified. All the available scientific literature dealing with this topic derives from studies not addressing this issue in HF, but in other settings, (e.g., arterial hypertension) and are also characterized by important methodological flaws. Thus, given the solid evidences arguing in favor of ß -blockers in HF in terms of morbidity, mortality and quality of life, ß -blockers at the maximal tolerated dosage in this patients' category should be recommended, regardless of ED. However, the ED-related issues should not be neglected, and adequate psychological counseling and management should be provided, pursuing the correction of risk factors, the choice of more suitable medications and, in selected cases, adopting specific drugs or devices. The purpose of this narrative review is to highlight the close relationship between ED and HF and, specifically, to focus on a possible ß -blockers' role in determining or, at least, worsening this condition.

"Interstitial fibrosis is associated with left atrial remodeling and adverse clinical outcomes in selected low-risk patients with hypertrophic cardiomyopathy".

BACKGROUND: Cardiovascular magnetic resonance (CMR) extracellular volume (ECV) allows non-invasive detection of myocardial interstitial fibrosis, which may be related to diastolic dysfunction and left atrial (LA) remodeling in hypertrophic cardiomyopathy (HCM). While the prognostic role of LGE is well-established, interstitial fibrosis and LA dysfunction are emerging novel markers in HCM. This study aimed to explore the interaction between interstitial fibrosis by ECV, LA morpho-functional parameters and adverse clinical outcomes in selected low-risk patients with HCM. METHODS: 115 HCM patients and 61 matched controls underwent CMR to identify: i) interstitial fibrosis by ECV in hypertrophied left ventricular LGE-negative remote myocardium (r-ECV); ii) LA indexed maximum (LAVi max) and minimum (LAVi min) volumes, ejection fraction (LA-EF) and strain (reservoir εs, conduit εe and booster εa), by CMR feature-tracking. 2D-echocardiographic assessment of diastolic function was also performed within 6 months from CMR. A composite endpoint including worsening NYHA class, heart failure hospitalization, atrial fibrillation and all-cause death was evaluated at 2.3 years follow-up. HCM patients were divided into two groups, according to r-ECV values of controls. RESULTS: Patients with r-ECV ≥29% (n = 45) showed larger LA volumes (LAVimax 63 vs. 54 ml/m2, p < 0.001; LAVimin 43 vs. 28 ml/m2, p ã€ˆ0001), worse LA function (εs 16 vs. 28%, εe 8 vs. 15%, εa 8 vs. 14%, LA-EF 33 vs. 49%, all p < 0.001) and elevated Nt-proBNP (1115 vs. 382 pg/ml, p = 0.002). LA functional parameters inversely correlated with r-ECV (εs r = -0.54; LA-EF r = -0.46; all p < 0.001) and E/e' (εs r = -0.52, LA-EF r = -0.46; all p < 0.006). r-ECV ≥29% and LAVi min >30 ml/m2 have been identified as possible independent factors associated with the endpoint. CONCLUSIONS: In HCM diffuse interstitial fibrosis detected by increased r-ECV is associated with LA remodeling and emerged as a potential independent predictor of adverse clinical outcomes, on top of the well-known prognostic impact of LGE.

Wild-Type Transthyretin Cardiac Amyloidosis is Not Rare in Elderly Subjects: the CATCH Screening Study.

BACKGROUND: Wild-type transthyretin cardiac amyloidosis (ATTRwt-CA) affects older adults and is currently considered as a rare disorder. OBJECTIVE: We investigated for the first time the prevalence of ATTRwt-CA in elderly individuals from the general population. METHODS: General practitioners from Pisa, Italy, proposed a screening for ATTRwt-CA to all their patients aged 65-90 years, until 1,000 accepted. The following red flags were searched: interventricular septal thickness ≥12 mm, any echocardiographic, ECG or clinical hallmark of CA, or high sensitivity-troponin T ≥14 ng/L. Individuals with at least one red flag (n=346) were asked to undergo the search for a monoclonal protein and bone scintigraphy, and 216 accepted. RESULTS: Four patients received a non-invasive diagnosis of ATTRwt-CA. All complained of dyspnea on moderate effort. A woman and a man aged 79 and 85 years, respectively, showed an intense cardiac tracer uptake (grade 3), left ventricular (LV) wall thickening, grade 2 to 3 diastolic dysfunction, and N-terminal pro-B-type natriuretic peptide (NT-proBNP) >1,000 ng/L. Two other patients (a man aged 74 years and a woman aged 83 years) showed a grade 2 uptake, an increased LV septal thickness, but preserved diastolic function, and NT-proBNP <300 ng/L. The prevalence of ATTR-CA in subjects ≥65 years was calculated as 0.46% (i.e., 4 out of the 870 subjects completing the screening, namely 654 not meeting the criteria for Step 2 and 216 progressing to Step 2). CONCLUSIONS: ATTRwt-CA is uncommon in elderly subjects from the general population, but more frequent than expected for a rare disease.

Wild-type transthyretin cardiac amyloidosis (ATTRwt-CA) is a heart condition mostly found in older adults. ATTRwt-CA is considered a rare disease, although no systematic screening have been performed yet. The study aimed to understand how common this disease is among the general population aged 65 to 90 years in Pisa, Italy. To do this, general practitioners offered screening for ATTRwt-CA to their patients within this age group. The initial step of the screening involved checking for certain warning signs (red flags), like abnormal thickness in a part of the heart called the interventricular septum, unusual heart function observed through various tests, or elevated levels of a specific heart protein. Out of 1,000 individuals who began the screening process, 346 showed at least one of these red flags and were further examined using bone scintigraphy (a type of imaging test) and tests for a specific protein related to this condition. Of these, 216 agreed to proceed with these additional tests. The results showed that four of these patients actually had ATTRwt-CA. Their conditions varied in severity, with some showing more intense signs of the disease on the heart scans, thicker heart walls, and higher levels of heart stress proteins. All four patients experienced mild difficulty in breathing during physical activity. Based on these findings, the study concluded that about 0.46% of elderly individuals in the general population might have ATTRwt-CA, indicating that the disease is somewhat more common in this age group than previously thought.

Eligibility for vericiguat in a real-world, contemporary heart failure population.

AIMS: Vericiguat is a soluble guanylate cyclase stimulator and improves survival in patients with heart failure (HF) with reduced ejection fraction (HFrEF) and an increased risk of decompensation. As real-world data on how many patients could be eligible for vericiguat therapy derive from outdated registries, we aimed to assess eligibility in a prospective cohort of patients with HF. METHODS AND RESULTS: Data from consecutive HF patients undergoing an elective ambulatory visit at five university hospitals from 3 July to 28 July 2023 were collected. Independent investigators assessed which patients (i) met the eligibility criteria of the VICTORIA trial, (ii) complied with HF guideline recommendations, (iii) met regulatory agency criteria, or (iv) met criteria for refundability according to the Italian regulatory agency. Patients (n = 346, 72% men, median age 69 years) had HFrEF in 57% of cases, left ventricular ejection fraction < 45% in 68%, and New York Heart Association class II-IV symptoms in 76%. Patients meeting the eligibility criteria of the VICTORIA trial or European and American HF Guideline recommendations were 9% and 13%, respectively. Patients meeting Food and Drug Administration (FDA) or European Medicines Agency (EMA) label criteria were 19% and 17%, respectively. Drug costs would be covered by the Italian National Health System in 10% of patients [if a sodium-glucose cotransporter-2 inhibitor (SGLT2i) is not mandatory] or in 8% (if an SGLT2i is requested). CONCLUSIONS: In a real-world study, 9% of patients met the eligibility criteria of the VICTORIA trial, but up to 13% complied with guideline recommendations and up to 19% met FDA or EMA criteria. In Italy, drug costs would be covered by up to 10% of patients.

European Society of Cardiology quality indicators update for the care and outcomes of adults with heart failure. The Heart Failure Association of the ESC.

AIMS: To update the European Society of Cardiology (ESC) quality indicators (QIs) for the evaluation of the care and outcomes of adults with heart failure. METHODS AND RESULTS: The Working Group comprised experts in heart failure including members of the ESC Clinical Practice Guidelines Task Force for heart failure, members of the Heart Failure Association, and a patient representative. We followed the ESC methodology for QI development. The 2023 focused guideline update was reviewed to assess the suitability of the recommendations with strongest association with benefit and harm against the ESC criteria for QIs. All the new proposed QIs were individually graded by each panellist via online questionnaires for both validity and feasibility. The existing heart failure QIs also underwent voting to 'keep', 'remove' or 'modify'. Five domains of care for the management of heart failure were identified: (1) structural QIs, (2) patient assessment, (3) initial treatment, (4) therapy optimization, and (5) patient health-related quality of life. In total, 14 'main' and 3 'secondary' QIs were selected across the five domains. CONCLUSION: This document provides an update of the previously published ESC QIs for heart failure to ensure that these measures are aligned with contemporary evidence. The QIs may be used to quantify adherence to clinical practice as recommended in guidelines to improve the care and outcomes of patients with heart failure.

Diabetic myocardial disorder. A clinical consensus statement of the Heart Failure Association of the ESC and the ESC Working Group on Myocardial & Pericardial Diseases.

The association between type 2 diabetes mellitus (T2DM) and heart failure (HF) has been firmly established; however, the entity of diabetic myocardial disorder (previously called diabetic cardiomyopathy) remains a matter of debate. Diabetic myocardial disorder was originally described as the occurrence of myocardial structural/functional abnormalities associated with T2DM in the absence of coronary heart disease, hypertension and/or obesity. However, supporting evidence has been derived from experimental and small clinical studies. Only a minority of T2DM patients are recognized as having this condition in the absence of contributing factors, thereby limiting its clinical utility. Therefore, this concept is increasingly being viewed along the evolving HF trajectory, where patients with T2DM and asymptomatic structural/functional cardiac abnormalities could be considered as having pre-HF. The importance of recognizing this stage has gained interest due to the potential for current treatments to halt or delay the progression to overt HF in some patients. This document is an expert consensus statement of the Heart Failure Association of the ESC and the ESC Working Group on Myocardial & Pericardial Diseases. It summarizes contemporary understanding of the association between T2DM and HF and discuses current knowledge and uncertainties about diabetic myocardial disorder that deserve future research. It also proposes a new definition, whereby diabetic myocardial disorder is defined as systolic and/or diastolic myocardial dysfunction in the presence of diabetes. Diabetes is rarely exclusively responsible for myocardial dysfunction, but usually acts in association with obesity, arterial hypertension, chronic kidney disease and/or coronary artery disease, causing additive myocardial impairment.

2023 Focused Update of the 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: Developed by the task force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC) With the special contribution of the Heart Failure Association (HFA) of the ESC.

Document Reviewers: Rudolf A. de Boer (CPG Review Co-ordinator) (Netherlands), P. Christian Schulze (CPG Review Co-ordinator) (Germany), Elena Arbelo (Spain), Jozef Bartunek (Belgium), Johann Bauersachs (Germany), Michael A. Borger (Germany), Sergio Buccheri (Sweden), Elisabetta Cerbai (Italy), Erwan Donal (France), Frank Edelmann (Germany), Gloria Färber (Germany), Bettina Heidecker (Germany), Borja Ibanez (Spain), Stefan James (Sweden), Lars Køber (Denmark), Konstantinos C. Koskinas (Switzerland), Josep Masip (Spain), John William McEvoy (Ireland), Robert Mentz (United States of America), Borislava Mihaylova (United Kingdom), Jacob Eifer Møller (Denmark), Wilfried Mullens (Belgium), Lis Neubeck (United Kingdom), Jens Cosedis Nielsen (Denmark), Agnes A. Pasquet (Belgium), Piotr Ponikowski (Poland), Eva Prescott (Denmark), Amina Rakisheva (Kazakhstan), Bianca Rocca (Italy), Xavier Rossello (Spain), Leyla Elif Sade (United States of America/Türkiye), Hannah Schaubroeck (Belgium), Elena Tessitore (Switzerland), Mariya Tokmakova (Bulgaria), Peter van der Meer (Netherlands), Isabelle C. Van Gelder (Netherlands), Mattias Van Heetvelde (Belgium), Christiaan Vrints (Belgium), Matthias Wilhelm (Switzerland), Adam Witkowski (Poland), and Katja Zeppenfeld (Netherlands) All experts involved in the development of this Focused Update have submitted declarations of interest. These have been compiled in a report and simultaneously published in a supplementary document to the Focused Update. The report is also available on the ESC website www.escardio.org/guidelines See the European Heart Journal online for supplementary documents that include evidence tables.

Right heart failure with left ventricular assist devices: Preoperative, perioperative and postoperative management strategies. A clinical consensus statement of the Heart Failure Association (HFA) of the ESC.

Right heart failure (RHF) following implantation of a left ventricular assist device (LVAD) is a common and potentially serious condition with a wide spectrum of clinical presentations with an unfavourable effect on patient outcomes. Clinical scores that predict the occurrence of right ventricular (RV) failure have included multiple clinical, biochemical, imaging and haemodynamic parameters. However, unless the right ventricle is overtly dysfunctional with end-organ involvement, prediction of RHF post-LVAD implantation is, in most cases, difficult and inaccurate. For these reasons optimization of RV function in every patient is a reasonable practice aiming at preparing the right ventricle for a new and challenging haemodynamic environment after LVAD implantation. To this end, the institution of diuretics, inotropes and even temporary mechanical circulatory support may improve RV function, thereby preparing it for a better adaptation post-LVAD implantation. Furthermore, meticulous management of patients during the perioperative and immediate postoperative period should facilitate identification of RV failure refractory to medication. When RHF occurs late during chronic LVAD support, this is associated with worse long-term outcomes. Careful monitoring of RV function and characterization of the origination deficit should therefore continue throughout the patient's entire follow-up. Despite the useful information provided by the echocardiogram with respect to RV function, right heart catheterization frequently offers additional support for the assessment and optimization of RV function in LVAD-supported patients. In any patient candidate for LVAD therapy, evaluation and treatment of RV function and failure should be assessed in a multidimensional and multidisciplinary manner.

A matter of sex-persistent predictive value of MECKI score prognostic power in men and women with heart failure and reduced ejection fraction: a multicenter study.

Background: A sex-based evaluation of prognosis in heart failure (HF) is lacking. Methods and results: We analyzed the Metabolic Exercise test data combined with Cardiac and Kidney Indexes (MECKI) score registry, which includes HF with reduced ejection fraction (HFrEF) patients. A cross-validation procedure was performed to estimate weights separately for men and women of all MECKI score parameters: left ventricular ejection fraction (LVEF), hemoglobin, kidney function assessed by Modification of Diet in Renal Disease, blood sodium level, ventilation vs. carbon dioxide production slope, and peak oxygen consumption (peakVO2). The primary outcomes were the composite of all-cause mortality, urgent heart transplant, and implant of a left ventricle assist device. The difference in predictive ability between the native and sex recalibrated MECKI (S-MECKI) was calculated using a receiver operating characteristic (ROC) curve at 2 years and a calibration plot. We retrospectively analyzed 7,900 HFrEF patients included in the MECKI score registry (mean age 61 ± 13 years, 6,456 men/1,444 women, mean LVEF 33% ± 10%, mean peakVO2 56.2% ± 17.6% of predicted) with a median follow-up of 4.05 years (range 1.72-7.47). Our results revealed an unadjusted risk of events that was doubled in men compared to women (9.7 vs. 4.1) and a significant difference in weight between the sexes of most of the parameters included in the MECKI score. S-MECKI showed improved risk classification and accuracy (area under the ROC curve: 0.7893 vs. 0.7799, p = 0.02) due to prognostication improvement in the high-risk settings in both sexes (MECKI score >10 in men and >5 in women). Conclusions: S-MECKI, i.e., the recalibrated MECKI according to sex-specific differences, constitutes a further step in the prognostic assessment of patients with severe HFrEF.

Prevention and rehabilitation after heart transplantation: A clinical consensus statement of the European Association of Preventive Cardiology, Heart Failure Association of the ESC, and the European Cardio Thoracic Transplant Association, a section of ESOT.

Little is known either about either physical activity patterns, or other lifestyle-related prevention measures in heart transplantation (HTx) recipients. The history of HTx started more than 50 years ago but there are still no guidelines or position papers highlighting the features of prevention and rehabilitation after HTx. The aims of this scientific statement are (i) to explain the importance of prevention and rehabilitation after HTx, and (ii) to promote the factors (modifiable/non-modifiable) that should be addressed after HTx to improve patients' physical capacity, quality of life and survival. All HTx team members have their role to play in the care of these patients and multidisciplinary prevention and rehabilitation programmes designed for transplant recipients. HTx recipients are clearly not healthy disease-free subjects yet they also significantly differ from heart failure patients or those who are supported with mechanical circulatory support. Therefore, prevention and rehabilitation after HTx both need to be specifically tailored to this patient population and be multidisciplinary in nature. Prevention and rehabilitation programmes should be initiated early after HTx and continued during the entire post-transplant journey. This clinical consensus.

Prevention and rehabilitation after heart transplantation: A clinical consensus statement of the European Association of Preventive Cardiology, Heart Failure Association of the ESC, and the European Cardio Thoracic Transplant Association, a section of ESOT.

Little is known either about either physical activity patterns, or other lifestyle-related prevention measures in heart transplantation (HTx) recipients. The history of HTx started more than 50 years ago but there are still no guidelines or position papers highlighting the features of prevention and rehabilitation after HTx. The aims of this scientific statement are (i) to explain the importance of prevention and rehabilitation after HTx, and (ii) to promote the factors (modifiable/non-modifiable) that should be addressed after HTx to improve patients' physical capacity, quality of life and survival. All HTx team members have their role to play in the care of these patients and multidisciplinary prevention and rehabilitation programmes designed for transplant recipients. HTx recipients are clearly not healthy disease-free subjects yet they also significantly differ from heart failure patients or those who are supported with mechanical circulatory support. Therefore, prevention and rehabilitation after HTx both need to be specifically tailored to this patient population and be multidisciplinary in nature. Prevention and rehabilitation programmes should be initiated early after HTx and continued during the entire post-transplant journey. This clinical consensus statement focuses on the importance and the characteristics of prevention and rehabilitation designed for HTx recipients.

OPTImal PHARMacological therapy for patients with heart failure: Rationale and design of the OPTIPHARM-HF registry.

AIMS: Patients with heart failure (HF) remain often undertreated for multiple reasons, including treatment inertia, contraindications, and intolerance. The OPTIimal PHARMacological therapy for patients with Heart Failure (OPTIPHARM-HF) registry is designed to evaluate the prevalence of evidence-based medical treatment prescription and titration, as well as the causes of its underuse, in a broad real-world population of consecutive patients with HF across the whole ejection fraction spectrum and among different clinical phenotypes. METHODS: The OPTIPHARM-HF registry (NCT06192524) is a prospective, multicenter, observational, national study of adult patients with symptomatic HF, as defined by current international guidelines, regardless of ejection fraction. Both outpatients and inpatients with chronic and acute decompensated HF will be recruited. The study will enroll up to 2500 patients with chronic HF at approximately 35 Italian HF centres. Patients will be followed for a maximum duration of 24 months. The primary objective of the OPTIPHARM-HF registry is to assess prescription and adherence to evidence-based guideline-directed medical therapy (GDMT) in patients with HF. The primary outcome is to describe the prevalence of GDMT use according to target guideline recommendation. Secondary objectives include implementation of comorbidity treatment, evaluation of sequence of treatment introduction and up-titration, description of GDMT implementation in the specific HF population, main causes of GDMT underuse, and assessment of cumulative rate of cardiovascular events. CONCLUSION: The OPTIPHARM-HF registry will provide important implications for improving patient care and adoption of recommended medical therapy into clinical practice among HF patients.

Integration of implantable device therapy in patients with heart failure. A clinical consensus statement from the Heart Failure Association (HFA) and European Heart Rhythm Association (EHRA) of the European Society of Cardiology (ESC).

Implantable devices form an integral part of the management of patients with heart failure (HF) and provide adjunctive therapies in addition to cornerstone drug treatment. Although the number of these devices is growing, only few are supported by robust evidence. Current devices aim to improve haemodynamics, improve reverse remodelling, or provide electrical therapy. A number of these devices have guideline recommendations and some have been shown to improve outcomes such as cardiac resynchronization therapy, implantable cardioverter-defibrillators and long-term mechanical support. For others, more evidence is still needed before large-scale implementation can be strongly advised. Of note, devices and drugs can work synergistically in HF as improved disease control with devices can allow for further optimization of drug therapy. Therefore, some devices might already be considered early in the disease trajectory of HF patients, while others might only be reserved for advanced HF. As such, device therapy should be integrated into HF care programmes. Unfortunately, implementation of devices, including those with the greatest evidence, in clinical care pathways is still suboptimal. This clinical consensus document of the Heart Failure Association (HFA) and European Heart Rhythm Association (EHRA) of the European Society of Cardiology (ESC) describes the physiological rationale behind device-provided therapy and also device-guided management, offers an overview of current implantable device options recommended by the guidelines and proposes a new integrated model of device therapy as a part of HF care.

Exploring the Prognostic Performance of MECKI Score in Heart Failure Patients with Non-Valvular Atrial Fibrillation Treated with Edoxaban.

INTRODUCTION: Risk stratification in heart failure (HF) is essential for clinical and therapeutic management. The Metabolic Exercise test data combined with Cardiac and Kidney Indexes (MECKI) score is a validated prognostic model for assessing cardiovascular risk in HF patients with reduced ejection fraction (HFrEF). From the validation of the score, the prevalence of HF patients treated with direct oral anticoagulants (DOACs), such as edoxaban, for non-valvular atrial fibrillation (NVAF) has been increasing in recent years. This study aims to evaluate the reliability of the MECKI score in HFrEF patients treated with edoxaban for NVAF. MATERIALS AND METHODS: This study included consecutive outpatients with HF and NVAF treated with edoxaban (n = 83) who underwent a cardiopulmonary exercise test (CPET). They were matched by propensity score with a retrospective group of HFrEF patients with NVAF treated with vitamin K antagonists (VKAs) from the MECKI score registry (n = 844). The study endpoint was the risk of cardiovascular mortality, urgent heart transplantation, or Left Ventricle Assist Device (LVAD) implantation. RESULTS: Edoxaban patients were treated with a more optimized HF therapy and had different clinical characteristics, with a similar MECKI score. After propensity score, 77 patients treated with edoxaban were successfully matched with the MECKI-VKA control cohort. In both groups, MECKI accurately predicted the composite endpoint with similar area under the curves (AUC = 0.757 vs. 0.829 in the MECKI-VKA vs. edoxaban-treated group, respectively, p = 0.452). The two populations' survival appeared non-significantly different at the 2-year follow-up. CONCLUSIONS: this study confirms the prognostic accuracy of the MECKI score in HFrEF patients with NVAF treated with edoxaban, showing improved predictive power compared to VKA-treated patients.