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Introduction: Diabetic cardiomyopathy in young patients with type 1 diabetes (T1D) usually presents as asymptomatic diastolic heart dysfunction with left ventricle (LV) remodeling. Its prevalence seems to be underestimated. One of the factors seemingly influencing LV remodeling is a metabolic-associated steatotic liver disease (MASLD), which was extensively investigated in patients with type 2 diabetes but not with T1D. This study aimed to describe the correlation between MASLD risk and relative wall thickness (RWT) in young patients with T1D without heart failure symptoms or treatment., Materials and Methods: Study participants were recruited at the inpatient diabetology department, in admission order. Patients underwent a set of laboratory tests and echocardiographic examinations. The risk of MASLD was estimated using fatty liver index (FLI). Acquired data was then statistically analyzed., Results: The study group consisted of 55 patients. 25 participants had RWT > 0.42, suggesting LV remodeling. Study participants did not differ in HbA1c, NT-proBNP, HDL, LDL, non-HDL, and uric acid concentrations. However, patients with RWT > 0.42 had higher FLI (40.97 vs. 13.82, p < 0.01) and BMI (27.3 vs. 22.5, p < 0.01) and differed in transaminase concentrations. Moreover, patients with RWT > 0.42 had significantly higher LV mass index (85.6 vs. 68.2 g/m2) and altered mitral ring velocities. In univariable logistic regression, FLI correlated with LV remodeling risk (OR 1.028, p = 0.05). The optimal cutoff point for FLI predicting the RWT > 0.42 was 26.38 (OR 10.6, p = 0.04, sensitivity 0.857, specificity 0.657)., Conclusions: FLI correlates with RWT in patients with T1D independently of diabetes metabolic control and hypothetically may support recognizing T1D patients with a higher risk of LV remodeling., (© 2024. The Author(s).)

Aims: Compared to heart failure (HF) with reduced ejection fraction, HF with preserved ejection fraction (HFpEF), and HF with mildly reduced ejection fraction (HFmrEF) are increasing in prevalence, yet little is known about the geographic variation in patient characteristics, treatments and outcomes among these two HF phenotypes. The aim of this study was to investigate geographic differences in HFpEF and HFmrEF., Methods and Results: We conducted an individual patient analysis of five clinical trials enrolling patients with HFpEF or HFmrEF from North America (NA), Latin America (LA), Western Europe (WE), Central/Eastern Europe and Russia (CEER), and Asia-Pacific (AP). We compared regions using descriptive statistics and multivariable regression models. Among the 19 959 patients included, 4066 (23.1%) had HFmrEF and 15 353 (76.9%) HFpEF. Regardless of HF phenotype, patients from WE were oldest, and those in CEER youngest. LA had the largest portion of females and NA most black patients. Obesity and diabetes were most prevalent in NA and hypertension and coronary heart disease most common in CEER. Self-reported health status varied strikingly and was the worst in NA and best in AP. Among patients with HFmrEF, rates of the primary composite endpoint (cardiovascular death or HF hospitalization) were: NA 12.56 per 100 patient-years (/100py), AP 11.67/100py, CEER 10.12/100py, LA 8.90/100py, and WE 8.43/100py, driven by differences in the rate of HF hospitalization. The corresponding values in HFpEF were 11.47/100py, 7.80/100py, 5.47/100py, 5.92/100py, and 7.80/100py, respectively., Conclusions: There is substantial geographic variation in patient characteristics, treatment and outcomes among patients with HFpEF and HFmrEF. These findings have implications for interpretation and generalizability of trial results, design and conduct of future trials, and optimization of care for these patients., (© 2024 The Author(s). European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Introduction: Type 1 diabetes (T1D) is a metabolic disease characterized by insulin deficiency and subsequent hyperglycemia. Cardiovascular diseases are the prime cause of mortality and morbidity among patients with T1D. Accumulating metabolic disturbances and accelerated cardiac fibrosis fuel the development of heart dysfunction. As insulin resistance (IR) is a risk factor for the development and worsened course of heart failure, this study aimed to assess its impact on heart function in patients with T1D., Methods: Adult participants were recruited prospectively. The inclusion criteria included a diagnosis of T1D. The exclusion criteria were other types of diabetes, symptoms/treatment of heart failure, AST and/or ALT exceeding the upper reference limit by ≥2x, hepatitis, alcoholism, metformin treatment, and pregnancy. The participants underwent a medical interview, physical examination, biochemical test, and echocardiography., Results: The mean age in the study group was 38 ± 9.6 years, and the mean diabetes duration was 21.8 ± 11.3 years. The median BMI in the study cohort was 23.39 kg/m 2 . Patients with IR had significantly lower mitral E/A ratio and left ventricular and left atrial volume ratio (LVLAVR), higher LV mass index, and presented with altered mitral annular velocities., Conclusions: IR seems to accelerate the pattern of typical changes in heart function among patients with T1D, especially in the overweight subgroup., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Czarnik, Sablik, Borkowska, Drożdż and Cypryk.)

Aim: COVID-19 may affect clinical risk in patients with heart failure. DELIVER began before and was conducted during the COVID-19 pandemic. This study aimed to evaluate the association between COVID-19 and clinical outcomes among DELIVER participants., Methods and Results: Participants with chronic heart failure with mildly reduced or preserved ejection fraction (HFmrEF/HFpEF) were randomized to dapagliflozin or placebo across 350 sites in 20 countries. COVID-19 was investigator-reported and the contribution of COVID-19 to death was centrally adjudicated. We assessed (i) the incidence of COVID-19, (ii) event rates before/during the pandemic, and (iii) risks of death after COVID-19 diagnosis compared to risks of death in participants without COVID-19. Further, we performed a sensitivity analysis assessing treatment effects of dapagliflozin vs. placebo censored at pandemic onset. Of 6263 participants, 589 (9.4%) developed COVID-19, of whom 307 (52%) required/prolonged hospitalization. A total of 155 deaths (15% of all deaths) were adjudicated as definitely/possibly COVID-19-related. COVID-19 cases and deaths did not differ by randomized assignment. Death rate in the 12 months following diagnosis was 56.1 (95% confidence interval [CI] 48.0-65.6) versus 6.4 (95% CI 6.0-6.8)/100 participant-years among trial participants with versus without COVID-19 (adjusted hazard ratio [aHR] 8.60, 95% CI 7.18-10.30). Risk was highest 0-3 months following diagnosis (153.5, 95% CI 130.3-180.8) and remained elevated at 3-6 months (12.6, 95% CI 6.6-24.3/100 participant-years). After excluding investigator-reported fatal COVID-19 events, all-cause death rates in the 12 months following diagnosis among COVID-19 survivors (n = 458) remained higher (aHR 2.46, 95% CI 1.83-3.33) than rates for all trial participants from randomization, with censoring of participants who developed COVID-19 at the time of diagnosis. Dapagliflozin reduced cardiovascular death/worsening HF events when censoring participants at COVID-19 diagnosis (HR 0.81, 95% CI 0.72-0.91) and pandemic onset (HR 0.72, 95% CI 0.58-0.89). There were no diabetic ketoacidosis or major hypoglycaemic events within 30 days of COVID-19., Conclusion: DELIVER is one of the most extensive experiences with COVID-19 of any cardiovascular trial, with >75% of follow-up time occurring during the pandemic. COVID-19 was common, with >50% of cases leading to hospitalization or death. Treatment benefits of dapagliflozin persisted when censoring at COVID-19 diagnosis and pandemic onset. Patients surviving COVID-19 had a high early residual risk., Clinical Trial Registration: ClinicalTrials.gov Identifier NCT03619213., (© 2023 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Articular cartilage lesions negatively affect patients' well-being, causing severe pain and significantly limiting functioning. The purpose of this study was to evaluate the effectiveness of a one-stage reconstruction, performed arthroscopically using a hyaluronate-based scaffold. Pain reduction and functional improvement were assessed. The study also evaluated if postoperative vitamin D supplementation and rehabilitation protocol impact obtained outcomes. A group of 29 patients was included in a retrospective study. All the participants underwent arthroscopic reconstruction of osteochondral lesions using hyaluronate-based scaffolds. The study group used standard questionnaires to self-assess their condition before surgery and at the time of completion. Despite the aforementioned, all the participants fulfilled two original questionnaires on postoperative rehabilitation and vitamin D supplementation. Significant pain reduction (mean NRS 1.83 vs. 7.21, p < 0.0001) and functional improvement (mean Lysholm score 82.38 vs. 40.38, p < 0.0001; mean OKS 40.2 vs. 23.1, p < 0.0001) were found. No differences in pain reduction and functional improvement were seen between genders. The impact of post-operative rehabilitation and vitamin D supplementation on clinical outcomes was found to be statistically nonsignificant. The results obtained in this study clearly confirm the effectiveness of osteochondral reconstruction using hyaluronate-based scaffolds. The outcomes were equally favorable, regardless of postoperative rehabilitation and vitamin D supplementation.

Cardiovascular diseases (CVDs) are the leading causes of death worldwide. CVDs have become the dominant cause of death and have been a significant health challenge since the second half of the 20th century in the Polish population. The aim of our HDMI (hospital diet medical investigation) study was to examine the quality of the hospital diets given to cardiac patients and assess how much they adhere to the European Society of Cardiology (ESC) 2021 guidelines. By comparing the diets received by patients with the recommended dietary patterns outlined in the ESC 2021 guidelines, we sought to identify discrepancies. The study was conducted in two steps: creating a 7-day model menu and comparing it with the received diets and then making comparisons with ESC 2021 guidelines. Additionally, we designed a survey to obtain the characteristics of the hospitals. The results show that the nutrition in hospitals remains substandard. None of the diets had an appropriate salt supply or predominance of plant-based food patterns. Only 1/7 diets avoided sweetened beverages, and 2/7 diets had an appropriate amount of fiber. This underscores a gap in the healthcare system to improve patients' health by implementing dietary interventions that foster the development of healthy eating habits.

Aims: To comprehensively assess hyponatraemia in acute heart failure (AHF) regarding prevalence, associations, hospital course, and post-discharge outcomes., Methods and Results: Of 8298 patients in the European Society of Cardiology Heart Failure Long-Term Registry hospitalized for AHF with any ejection fraction, 20% presented with hyponatraemia (serum sodium <135 mmol/L). Independent predictors included lower systolic blood pressure, estimated glomerular filtration rate (eGFR) and haemoglobin, along with diabetes, hepatic disease, use of thiazide diuretics, mineralocorticoid receptor antagonists, digoxin, higher doses of loop diuretics, and non-use of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers and beta-blockers. In-hospital death occurred in 3.3%. The prevalence of hyponatraemia and in-hospital mortality with different combinations were: 9% hyponatraemia both at admission and discharge (hyponatraemia Yes/Yes, in-hospital mortality 6.9%), 11% Yes/No (in-hospital mortality 4.9%), 8% No/Yes (in-hospital mortality 4.7%), and 72% No/No (in-hospital mortality 2.4%). Correction of hyponatraemia was associated with improvement in eGFR. In-hospital development of hyponatraemia was associated with greater diuretic use and worsening eGFR but also more effective decongestion. Among hospital survivors, 12-month mortality was 19% and adjusted hazard ratios (95% confidence intervals) were for hyponatraemia Yes/Yes 1.60 (1.35-1.89), Yes/No 1.35 (1.14-1.59), and No/Yes 1.18 (0.96-1.45). For death or heart failure hospitalization they were 1.38 (1.21-1.58), 1.17 (1.02-1.33), and 1.09 (0.93-1.27), respectively., Conclusion: Among patients with AHF, 20% had hyponatraemia at admission, which was associated with more advanced heart failure and normalized in half of patients during hospitalization. Admission hyponatraemia (possibly dilutional), especially if it did not resolve, was associated with worse in-hospital and post-discharge outcomes. Hyponatraemia developing during hospitalization (possibly depletional) was associated with lower risk., (© 2023 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background: Insulin-like growth factor-binding protein-7 (IGFBP-7) has been proposed as a potential prognostic biomarker in heart failure (HF), but the association between elevation in IGFBP-7 and HF outcomes in ambulant patients with heart failure with reduced ejection fraction (HFrEF) is unknown., Objectives: The authors addressed this question in a post hoc analysis of the DAPA-HF (Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure) trial., Methods: The primary outcome was a composite of cardiovascular death or a worsening HF event. The risk of adverse outcome was compared across tertiles of IGFBP-7 concentration by means of Cox proportional hazard models adjusted for N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity troponin T (hsTnT). The efficacy of randomized treatment across IGFBP-7 tertiles was assessed. Change in IGFBP-7 at 12 months was compared with the use of geometric means., Results: A total of 3,158 patients had IGFBP-7 measured at baseline, and 2,493 had a repeated measure at 12 months. Patients in the highest tertile of IGFBP-7 had evidence of more advanced HFrEF. The adjusted HR for the primary endpoint in tertile 3, compared with tertile 1, was 1.48 (95% CI: 1.17-1.88). There was no modification of the benefit of dapagliflozin by baseline IGFBP-7 (P interaction = 0.34). Dapagliflozin did not change IGFBP-7 levels over 1 year (P = 0.34)., Conclusions: Higher IGFBP-7 in patients with HFrEF was associated with worse clinical profile and an increased risk of adverse clinical outcomes. IGFBP-7 provided prognostic information incremental to clinical variables, NT-proBNP, and hsTnT. The benefit of dapagliflozin was not modulated by IGFBP-7 level. (Study to Evaluate the Effect of Dapagliflozin on the Incidence of Worsening Heart Failure or Cardiovascular Death in Patients With Chronic Heart Failure [DAPA-HF]; NCT03036124)., Competing Interests: Funding Support and Author Disclosures The DAPA-HF trial was funded by AstraZeneca. Drs Adamson and McMurray are supported by British Heart Foundation Centre of Research Excellence grant RE/18/6/34217. Dr Welsh has received grant income from RocheDiagnostics, AstraZeneca, Boehringer Ingelheim, and Novartis outside the submitted work. Dr Docherty’s employer, the University of Glasgow, has been remunerated by AstraZeneca for working on the DAPA-HF trial, and he has received personal fees from AstraZeneca and Eli Lilly outside of the submitted work. Dr de Boer has received research grants and/or fees to his institution from AstraZeneca, Abbott, Boehringer Ingelheim, Cardior Pharmaceuticals, Ionis Pharmaceuticals, Novo Nordisk, and Roche outside of the submitted work; and has received speaker fees from Abbott, AstraZeneca, Bayer, Novartis, and Roche outside of the submitted work. Dr Diez has received personal fees from AstraZeneca during the conduct of the study. Dr Inzucchi has membership on scientific/research advisory boards for Boehringer Ingelheim, AstraZeneca, Intarcia, Lexicon, Janssen, Sanofi, Merck & Co, and Novo Nordisk; has received research supplies to Yale University from Takeda; and has participated in medical educational projects for which unrestricted funding from Boehringer Ingelheim, Eli Lilly, and Merck & Co was received by Yale University. Dr Køber has received speaker honoraria from Novartis, AstraZeneca, Novo, and Boehringer Ingelheim. Dr Kosiborod has received grant and research support from AstraZeneca; grant and honoraria from Boehringer Ingelheim; and honoraria from Sanofi, Amgen, Novo Nordisk, Merck (Diabetes), Janssen, Bayer, Novartis, Eli Lilly, and Vifor Pharma. Dr Ljungman has received personal fees and financial reimbursement through her institution from AstraZeneca during the conduct of the study and personal fees from Novartis and Pfizer outside of the submitted work. Dr Martinez has received personal fees from AstraZeneca during the conduct of the study. Dr Ponikowski has received personal fees for consultancy and Speakers Bureau from AstraZeneca, Boehringer Ingelheim, Vifor Pharma, Servier, Bayer, Bristol Myers Squibb, Respocardia, Berlin-Chemie, Cibiem, Novartis, and RenalGuard; other support for participation in clinical trials from Boehringer Ingelheim, Amgen, Vifor Pharma, Bayer, Bristol Myers Squibb, Cibiem, Novartis, and RenalGuard; and research grants to his institution from Vifor Pharma. Dr Sabatine has received research grant support through Brigham and Women’s Hospital from Amgen, Anthos Therapeutics, AstraZeneca, Bayer, Daiichi Sankyo, Eisai, Intarcia, Medicines Company, MedImmune, Merck, Novartis, Pfizer, Quark Pharmaceuticals, and Takeda; and has done consulting for Althera, Amgen, Anthos Therapeutics, AstraZeneca, Bristol-Myers Squibb, CVS Caremark, DalCor, Dr Reddy’s Laboratories, Dyrnamix, Esperion, IFM Therapeutics, Intarcia, Janssen Research and Development, The Medicines Company, MedImmune, Merck, and Novartis. Dr Morrow has received grants to the TIMI Study Group from Abbott Laboratories, Amgen, Anthos Therapeutics, AstraZeneca, BRAHMS, Eisai, GlaxoSmithKline, The Medicines Company, Merck, Novartis, Pfizer, Roche Diagnostics, Quark, Siemens, and Takeda; and has received consultant fees from InCardia, Merck & Co, Novartis, and Roche Diagnostics. Drs Sabatine and Morrow are members of the TIMI Study Group, which has received institutional research grant support through Brigham and Women’s Hospital from Abbott, Amgen, Anthos Therapeutics, ARCA Bio-pharma, AstraZeneca, Bayer, Daiichi-Sankyo, Eisai, Intarcia, Ionis Pharmaceuticals, MedImmune, Merck, Novartis, Pfizer, Quark Pharmaceuticals, Regeneron Pharmaceuticals, Roche, Siemens Healthcare Diagnostics, The Medicines Company, and Zora Biosciences. Drs Lindholm, Hammarstedt, Boulton, Greasley, and Langkilde are employees and/or shareholders of AstraZeneca. Dr Boutlon is a stockholder of Bristol-Myers Squibb Company. Dr Solomon has received payment to his institution for participation in DAPA-HF; has received grants through his institution from Actelion, Alnylam, Amgen, AstraZeneca, Bellerophon, Bayer, Bristol Myers Squibb, Celladon, Cytokinetics, Eidos, Gilead, GlaxoSmithKline, IONIS, Lilly, Mesoblast, MyoKardia, National Institutes of Health National Heart, Lung, and Blood Institute, Neurotronik, Novartis, Novo Nordisk, Respicardia, Sanofi Pasteur, Theracos, and US2.AI; has received fees for consultancy from Abbott, Action, Akros, Alny-lam, Amgen, Arena, AstraZeneca, Bayer, Boehringer-Ingelheim, Bristol Myers Squibb, Cardior, Cardurion, Corvia, Cytokinetics, Daiichi-Sankyo, GlaxoSmithKline, Lilly, Merck, Myokardia, Novartis, Roche, Theracos, Quantum Genomics, Cardurion, Janssen, Cardiac Dimensions, Tenaya, Sanofi Pasteur, Dinaqor, Tremeau, CellProThera, Moderna, American Regent, and Sarepta; and has received honoraria for lectures from Novartis and AstraZeneca. Dr Sattar has consulted for Amgen, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Merck Sharp and Dohme, Novo Nordisk, Novartis, Sanofi, and Pfizer; and has received grant support from Boehringer Ingelheim. Dr McMurray’s employer, the University of Glasgow, has received payment for his work on clinical trials, consulting, and other activities from Alnylam, Amgen, AstraZeneca, Bayer, Bristol Myers Squibb, Cardurion, Cytokinetics, GlaxoSmithKline, Novartis, Pfizer, Theracos; and he has received personal lecture fees from the Corpus, Abbott, Hickma, Sun Pharmaceuticals, and Medscape. Dr Jhund’s employer, the University of Glasgow, has been remunerated by AstraZeneca for working on the DAPA-HF trial and the DELIVER trial; and he has received speaker and advisory board fees from AstraZeneca, speaker and advisory board fees from Novartis, and advisory board fees and grants from Boehringer Ingelheim. All other authors have reported no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Aims: We tested the hypothesis that initiation versus non-initiation of sacubitril/valsartan is associated with a more favorable subsequent change in left ventricular ejection fraction (LVEF) in a real-world setting., Methods: A prospective, non-randomized, double-arm, open-label, cohort study had been conducted across 687 centers in 17 European countries enrolling HFrEF patients aged ≥18 years with symptoms of HF (New York Heart Association [NYHA] II-IV) and "reduced LVEF". For the current analysis, 2602 patients with LVEF measured at baseline and follow-up were chosen, of which 860 (33%, mean age 67 years, 26% women) were started on sacubitril/valsartan at baseline and 1742 (67%, 68 years, 23% women) were not. Patients started on sacubitril/valsartan had higher NYHA class and lower LVEF., Results: LVEF increased from mean 32.7% to 38.1% in the sacubitril/valsartan group versus from 35.9% to 38.7% in the non-sacubitril/valsartan group (mean difference in increase 2.6%, p < 0.001). LVEF increased from baseline in 64% versus 53% of patients and increased by ≥5% (absolute %) in 50% versus 35% of patients in the sacubitril/valsartan versus non-sacubitril/valsartan groups, respectively. In the overall cohort, initiation of sacubitril/valsartan was independently associated with any increase in LVEF (adjusted odds ratio [OR] 1.49 [1.26-1.75]) and with increase by ≥5% (OR 1.65 [1.39-1.95])., Conclusion: Initiating versus not initiating sacubitril/valsartan was independently associated with a greater subsequent increase in LVEF in this real-world setting. Reverse cardiac remodeling may be one mechanism of benefit of sacubitril/valsartan., Competing Interests: Declaration of Competing Interest LHL reports research grants from AstraZeneca, Novartis, Boehringer Ingelheim, Vifor-Fresenius, and Boston Scientific; consulting or speaker's honoraria from AstraZeneca, Novartis, Boehringer Ingelheim, Vifor-Fresenius, Bayer, Pharmacosmos, Abbott, Sanofi, Merck, Myokardia, Orion Pharma, MedScape, Radcliffe Cardiology, Lexicon, and Respicardia; and stock ownership in AnaCardio; outside the submitted work. UZ has received research funding as well as speaker and consulting honoraria from Novartis. ALC has received funding for travel to meetings from Novartis as well as unrestricted grants for the support of his department. VB has received funding for travel to meetings from Novartis as well as fees for lectures and unrestricted grants for clinical research. JD has received honoraria for participation in committees of studies sponsored by Novartis. CF has received speaker fees and honoraria for consulting from Novartis, Servier, Bayer, OMPharma, and Daiichi Sankyo. SK is an employee of GKM (clinical research organization) contracted for data analysis by Novartis. PCF and CK are employees of Novartis. APM has received personal fees for participation in study committees of trials funded by Novartis, Bayer, Cardiorentis, and Fresenius., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Several mechanisms have been suggested to explain positive cardiovascular effects observed in studies with sodium-glucose co-transporter 2 (SGLT2) inhibitors. The reduction in glucose reabsorption in proximal tubuli induced by SGLT2 inhibitors increases urinary glucose and sodium excretion resulting in increased osmotic diuresis and consequently in decreased plasma volume, followed by reduced preload. In addition, the hemodynamic effects of SGLT2 inhibition were observed in both hyper and euglycemic patients. Due to the complex and multidirectional effects induced by SGLT2 inhibitors, this originally antidiabetic group of drugs has been successfully used to treat patients with heart failure as well as for subjects with chronic kidney disease. Moreover, their therapeutic potential seems to be even broader than the indications studied to date.

Heart failure (HF) remains one of the most common causes of hospitalization and mortality among Polish patients. The position of the Section of Cardiovascular Pharmacotherapy presents the currently applicable options for pharmacological treatment of HF based on the latest European and American guidelines from 2021-2022 in relation to Polish healthcare conditions. Treatment of HF varies depending on its clinical presentation (acute/chronic) or left ventricular ejection fraction. Initial treatment of symptomatic patients with features of volume overload is based on diuretics, especially loop drugs. Treatment aimed at reducing mortality and hospitalization should include drugs blocking the renin-angiotensin-aldosterone system, preferably angiotensin receptor antagonist/neprilysin inhibitor, i.e. sacubitril/valsartan, selected beta-blockers (no class effect - options include bisoprolol, metoprolol succinate, or vasodilatory beta-blockers - carvedilol and nebivolol), mineralocorticoid receptor antagonist, and sodium-glucose cotransporter type 2 inhibitor (flozin), constituting the 4 pillars of pharmacotherapy. Their effectiveness has been confirmed in numerous prospective randomized trials. The current HF treatment strategy is based on the fastest possible implementation of all four mentioned classes of drugs due to their independent additive action. It is also important to individualize therapy according to comorbidities, blood pressure, resting heart rate, or the presence of arrhythmias. This article emphasizes the cardio- and nephroprotective role of flozins in HF therapy, regardless of ejection fraction value. We propose practical guidelines for the use of medicines, profile of adverse reactions, drug interactions, as well as pharmacoeconomic aspects. The principles of treatment with ivabradine, digoxin, vericiguat, iron supplementation, or antiplatelet and anticoagulant therapy are also discussed, along with recent novel drugs including omecamtiv mecarbil, tolvaptan, or coenzyme Q10 as well as progress in the prevention and treatment of hyperkalemia. Based on the latest recommendations, treatment regimens for different types of HF are discussed.

Respiratory diseases have been the fourth most common cause of death in Poland in recent years. Respiratory infection, especially pneumonia, can lead to exacerbation of chronic cardiovascular disease.Streptococcus pneumoniae is the most common bacterial pathogen causing community-acquired pneumonia. Pneumococci are also the most common pathogen complicating the course of infection with the influenza virus. Pneumonia, especially invasive pneumococcal disease, is associated with risk of death in the course of respiratory failure or sepsis and also with worsening of the prognosis for existing cardiovascular disease. Despite those facts, recommendations for pneumococcal vaccination are still not well established in cardiovascular guidelines. This expert opinion aims to summarize current knowledge on the importance of preventing invasive pneumococcal disease in cardiac patients.

Background: Since the beginning of the coronavirus disease 2019 (COVID-19) pandemic, numerous cardiology departments were reorganized to provide care for COVID-19 patients. We aimed to compare the impact of the COVID-19 pandemic on hospital admissions and in-hospital mortality in reorganized vs. unaltered cardiology departments., Methods: The present research is a subanalysis of a multicenter retrospective COV-HF-SIRIO 6 study that includes all patients (n = 101,433) hospitalized in 24 cardiology departments in Poland between January 1, 2019 and December 31, 2020, with a focus on patients with acute heart failure (AHF)., Results: Reduction of all-cause hospitalizations was 50.6% vs. 21.3% for reorganized vs. unaltered cardiology departments in 2020 vs. 2019, respectively (p < 0.0001). Considering AHF alone respective reductions by 46.5% and 15.2% were registered (p < 0.0001). A higher percentage of patients was brought in by ambulance to reorganized vs. unaltered cardiology departments (51.7% vs. 34.6%; p < 0.0001) alongside with a lower rate of self-referrals (45.7% vs. 58.4%; p < 0.0001). The rate of all-cause in-hospital mortality in AHF patients was higher in reorganized than unaltered cardiology departments (10.9% vs. 6.4%; p < 0.0001). After the exclusion of patients with concomitant COVID-19, the mortality rates did not differ significantly (6.9% vs. 6.4%; p = 0.55)., Conclusions: A greater reduction in hospital admissions in 2020 vs. 2019, higher rates of patients brought by ambulance together with lower rates of self-referrals and higher all-cause in-hospital mortality for AHF due to COVID-19 related deaths were observed in cardiology departments reorganized to provide care for COVID-19 patients vs. unaltered ones.

Background: Frailty is increasing in prevalence. Because patients with frailty are often perceived to have a less favorable risk/benefit profile, they may be less likely to receive new pharmacologic treatments. We investigated the efficacy and tolerability of dapagliflozin according to frailty status in patients with heart failure with mildly reduced or preserved ejection fraction randomized in DELIVER (Dapagliflozin Evaluation to Improve the Lives of Patients With Preserved Ejection Fraction Heart Failure)., Methods: Frailty was measured using the Rockwood cumulative deficit approach. The primary end point was time to a first worsening heart failure event or cardiovascular death., Results: Of the 6263 patients randomized, a frailty index (FI) was calculable in 6258. In total, 2354 (37.6%) patients had class 1 frailty (FI ≤0.210; ie, not frail), 2413 (38.6%) had class 2 frailty (FI 0.211-0.310; ie, more frail), and 1491 (23.8%) had class 3 frailty (FI ≥0.311; ie, most frail). Greater frailty was associated with a higher rate of the primary end point (per 100 person-years): FI class 1, 6.3 (95% CI 5.7-7.1); class 2, 8.3 (7.5-9.1); and class 3, 13.4 (12.1-14.7; P <0.001). The effect of dapagliflozin (as a hazard ratio) on the primary end point from FI class 1 to 3 was 0.85 (95% CI, 0.68-1.06), 0.89 (0.74-1.08), and 0.74 (0.61-0.91), respectively ( P interaction =0.40). Although patients with a greater degree of frailty had worse Kansas City Cardiomyopathy Questionnaire scores at baseline, their improvement with dapagliflozin was greater than it was in patients with less frailty: placebo-corrected improvement in Kansas City Cardiomyopathy Questionnaire Overall Summary Score at 4 months in FI class 1 was 0.3 (95% CI, -0.9 to 1.4); in class 2, 1.5 (0.3-2.7); and in class 3, 3.4 (1.7-5.1; P interaction =0.021). Adverse reactions and treatment discontinuation, although more frequent in patients with a greater degree of frailty, were not more common with dapagliflozin than with placebo irrespective of frailty class., Conclusions: In DELIVER, frailty was common and associated with worse outcomes. The benefit of dapagliflozin was consistent across the range of frailty studied. The improvement in health-related quality of life with dapagliflozin occurred early and was greater in patients with a higher level of frailty., Registration: URL: https://www., Clinicaltrials: gov; Unique identifier: NCT03619213.

Aims: Reflecting both increased venous pressure and reduced cardiac output, abnormal liver tests are common in patients with severe heart failure and are associated with adverse clinical outcomes. We aimed to investigate the prognostic significance of abnormal liver tests in ambulatory patients with heart failure with reduced ejection fraction (HFrEF), explore any treatment interaction between bilirubin and sodium-glucose cotransporter 2 (SGLT2) inhibitors and examine change in liver tests with SGLT2 inhibitor treatment., Methods and Results: We explored these objectives in the Dapagliflozin And Prevention of Adverse outcomes in Heart Failure (DAPA-HF) trial, with focus on bilirubin. We calculated the incidence of cardiovascular death or worsening heart failure by bilirubin tertile. Secondary cardiovascular outcomes were examined, along with the change in liver tests at the end-of-study visit. Baseline bilirubin was available in 4720 patients (99.5%). Participants in the highest bilirubin tertile (T3) have more severe HFrEF (lower left ventricular ejection fraction, higher N-terminal pro-B-type natriuretic peptide [NT-proBNP] and worse New York Heart Association class), had a greater burden of atrial fibrillation but less diabetes. Higher bilirubin (T3 vs. T1) was associated with worse outcomes even after adjustment for other predictive variables, including NT-proBNP and troponin T (adjusted hazard ratio for the primary outcome 1.73 [95% confidence interval 1.37-2.17], p < 0.001; and 1.52 [1.12-2.07], p = 0.01 for cardiovascular death). Baseline bilirubin did not modify the benefits of dapagliflozin. During follow-up, dapagliflozin had no effect on liver tests., Conclusion: Bilirubin concentration was an independent predictor of worse outcomes but did not modify the benefits of dapagliflozin in HFrEF. Dapagliflozin was not associated with change in liver tests., Clinical Trial Registration: ClinicalTrials.gov NCT03036124., (© 2022 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background: Higher resting heart rate (HR) in patients with heart failure (HF) and sinus rhythm (SR) is associated with increased mortality. In patients hospitalized for HF, the aim herein, was to assess the use and dosage of guideline-recommended HR lowering medications, HR control at discharge and predictors of HR control., Methods: In the present study, were Polish participants of the European Society of Cardiology HF Long-Term (ESC-HF-LT) Registry. Those selected were hospitalized for HF, with reduced ejection fraction (HFrEF) and SR at discharge (n = 236). The patients were divided in two groups ( < 70 and ≥ 70 bpm). Logistic regression was used to identify the predictors of HR ≥ 70 bpm., Results: Of patients with HFrEF and SR, 59% had HR ≥ 70 bpm at hospital discharge. At discharge, 96% and only 0.5% of the patients with HFrEF and SR received beta-blocker and ivabradine, respectively. In the HF groups < 70 and ≥ 70 bpm, only 11% and 4% of patients received beta-blocker target doses, respectively. There was no difference in the use of other guideline-recommended medications. Age, New York Heart Association class, HR on admission and lack of HR lowering medications were predictors of discharge HR ≥ 70 bpm., Conclusions: Heart rate control after hospitalization for HFrEF is unsatisfactory, which may be attributed to suboptimal doses of beta-blockers, and negligence in use other HR lowering drugs (including ivabradine).

Aims: To compare baseline characteristics of patients with heart failure with reduced ejection fraction (HFrEF) initiated on sacubitril/valsartan compared with patients continued on conventional heart failure (HF)-treatment in a European out-patient setting., Methods and Results: Between July 2016 and July 2019, ARIADNE enrolled 8787 outpatients aged ≥18 years with HFrEF from 17 European countries. Choice of therapy was solely at the investigators' discretion. In total, 4173 patients were on conventional HF-treatment (non-S/V group), while 4614 patients were on sacubitril/valsartan either at enrolment or started sacubitril/valsartan within 1 month of enrolment (S/V group). Of these, 2108 patients started sacubitril/valsartan treatment ±1 month around enrolment [restricted S/V (rS/V) group]. The average age of the patients was 68 years. Patients on S/V were more likely to have New York Heart Association (NYHA) class III or IV symptoms (50.3%, 44.6%, 32.1% in rS/V, S/V, and non-S/V, respectively) and had lower left ventricular ejection fraction (LVEF; 32.3%, 32.7%, and 35.4% in rS/V, S/V, and non-S/V, respectively; P < 0.0001). The most frequently received HF treatments were angiotensin-converting enzyme inhibitor/angiotensin receptor blocker (ACEI/ARB; ∼84% in non-S/V), followed by β-blockers (∼80%) and mineralocorticoid receptor antagonists (MRAs; 53%). The use of triple HF therapy (ACEI/ARB/angiotensin receptor neprilysin inhibitor with β-blockers and MRA) was higher in the S/V groups than non-S/V group (48.2%, 48.2%, and 40.2% in rS/V, S/V, and non-S/V, respectively)., Conclusion: In this large multinational HFrEF registry, patients receiving sacubitril/valsartan tended to be younger with lower LVEF and higher NYHA class. Fewer than half of the patients received triple HF therapy., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.)

Cardiac resynchronization therapy (CRT) applied to selected patients with heart failure (HF) improves their prognosis. In recent years, eligibility criteria for CRT have regularly changed. This study aimed to investigate the changes in eligibility of real-life HF patients for CRT over the past fifteen years. We reviewed European and North American guidelines from this period and applied them to HF patients from the ESC-HF Pilot and ESC-Long-Term Registries. Taking into consideration the criteria assessed in this study (including all classes of recommendations i.e., class I, IIa and IIb, as well as patients with AF and SR), the 2013 (ESC) guidelines would have qualified the most patients for CRT (266, 18.3%), while the 2015 (ESC) guidelines would have qualified the least (115, 7.9%; p-value for differences between all analyzed papers <0.0001). There were only 26 patients (1.8%) who would be eligible for CRT using the class I recommendations across all of the guidelines. These results demonstrate the variability in recommendations for CRT over the years. Moreover, this data indicates underuse of this form of pacing in HF and highlights the need for more studies in order to improve the outcomes of HF patients and further personalize their management.

Background: Frailty may modify the risk-benefit profile of certain treatments, and frail patients may have reduced tolerance to treatments., Objective: To investigate the efficacy of dapagliflozin according to frailty status, using the Rockwood cumulative deficit approach, in DAPA-HF (Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure)., Design: Post hoc analysis of a phase 3 randomized clinical trial. (ClinicalTrials.gov: NCT03036124)., Setting: 410 sites in 20 countries., Patients: Patients with symptomatic heart failure (HF) with a left ventricular ejection fraction of 40% or less and elevated natriuretic peptide., Intervention: Addition of once-daily 10 mg of dapagliflozin or placebo to guideline-recommended therapy., Measurements: The primary outcome was worsening HF or cardiovascular death., Results: Of the 4744 patients randomly assigned in DAPA-HF, a frailty index (FI) was calculable in 4742. In total, 2392 patients (50.4%) were in FI class 1 (FI ≤0.210; not frail), 1606 (33.9%) in FI class 2 (FI 0.211 to 0.310; more frail), and 744 (15.7%) in FI class 3 (FI ≥0.311; most frail). The median follow-up time was 18.2 months. Dapagliflozin reduced the risk for worsening HF or cardiovascular death, regardless of FI class. The differences in event rate per 100 person-years for dapagliflozin versus placebo from lowest to highest FI class were -3.5 (95% CI, -5.7 to -1.2), -3.6 (CI, -6.6 to -0.5), and -7.9 (CI, -13.9 to -1.9). Consistent benefits were observed for other clinical events and health status, but the absolute reductions were generally larger in the most frail patients. Study drug discontinuation and serious adverse events were not more frequent with dapagliflozin than placebo, regardless of FI class., Limitation: Enrollment criteria precluded the inclusion of very high-risk patients., Conclusion: Dapagliflozin improved all outcomes examined, regardless of frailty status. However, the absolute reductions were larger in more frail patients., Primary Funding Source: AstraZeneca.

Personalized management involving heart failure (HF) etiology is crucial for better prognoses for HF patients. This study aimed to compare patients with ischemic cardiomyopathy (ICM) and patients with non-ischemic dilated cardiomyopathy (NIDCM) in terms of baseline characteristics and prognosis. We assessed 895 patients with HF with reduced left ventricular ejection fraction participating in the Polish part of the European Society of Cardiology (ESC)-HF registries. ICM was present in 583 patients (65%), NIDCM in 312 patients (35%). The ICM patients were older ( p < 0.001) and had more comorbidities. The NIDCM patients more frequently had atrial fibrillation ( p = 0.04) and lower LVEF ( p = 0.01); therefore, they were treated more often with anticoagulants ( p = 0.01) and digitalis ( p < 0.001). The NIDCM patients were prescribed aldosterone antagonists more often ( p = 0.01). There were no other differences as regards the use of HF guideline-recommended medications, implantable cardioverter defibrillators or cardiac resynchronization therapy. The ICM patients were more likely to be treated with statins ( p < 0.001) and antiplatelet agents ( p < 0.001). All-cause death, as well as all-cause death and readmissions for HF at 12 months, occurred more often in the ICM group compared with the NIDCM group (15.9% vs. 10%, p = 0.016; and 40.9% vs. 28.6%, p = 0.00089, respectively). ICM etiology was an independent predictor of the composite endpoint in the total cohort ( p = 0.003). The ICM patients were older and had more comorbidities, whereas the NIDCM patients had lower LVEF. One-year prognosis was worse in the ICM patients than in the NIDCM patients. ICM etiology was independently associated with a worse one-year outcome.

Aims: The coronavirus disease-2019 (COVID-19) pandemic has changed the landscape of medical care delivery worldwide. We aimed to assess the influence of COVID-19 pandemic on hospital admissions and in-hospital mortality rate in patients with acute heart failure (AHF) in a retrospective, multicentre study., Methods and Results: From 1 January 2019 to 31 December 2020, a total of 101 433 patients were hospitalized in 24 Cardiology Departments in Poland. The number of patients admitted due to AHF decreased by 23.4% from 9853 in 2019 to 7546 in 2020 (P < 0.001). We noted a significant reduction of self-referrals in the times of COVID-19 pandemic accounting 27.8% (P < 0.001), with increased number of AHF patients brought by an ambulance by 15.9% (P < 0.001). The length of hospital stay was overall similar (7.7 ± 2.8 vs. 8.2 ± 3.7 days; P = not significant). The in-hospital all-cause mortality in AHF patients was 444 (5.2%) in 2019 vs. 406 (6.5%) in 2020 (P < 0.001). A total number of AHF patients with concomitant COVID-19 was 239 (3.2% of AHF patients hospitalized in 2020). The rate of in-hospital deaths in AHF patients with COVID-19 was extremely high accounting 31.4%, reaching up to 44.1% in the peak of the pandemic in November 2020., Conclusions: Our study indicates that the COVID-19 pandemic led to (i) reduced hospital admissions for AHF; (ii) decreased number of self-referred AHF patients and increased number of AHF patients brought by an ambulance; and (iii) increased in-hospital mortality for AHF with very high mortality rate for concomitant AHF and COVID-19., (© 2021 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Aims: To perform a comprehensive characterization of acute heart failure (AHF) with preserved (HFpEF), versus mildly reduced (HFmrEF) versus reduced ejection fraction (HFrEF)., Methods and Results: Of 5951 participants in the ESC HF Long-Term Registry hospitalized for AHF (acute coronary syndromes excluded), 29% had HFpEF, 18% HFmrEF, and 53% HFrEF. Hospitalization reasons were most commonly atrial fibrillation (more in HFmrEF and HFpEF), followed by ischaemia (HFmrEF), infection (HFmrEF and HFpEF), worsening renal function (HFrEF), and uncontrolled hypertension (HFmrEF and HFpEF). Hospitalization characteristics included lower blood pressure, more oedema and higher natriuretic peptides with lower ejection fraction, similar pulmonary congestion, more mitral regurgitation in HFrEF and HFmrEF and more tricuspid regurgitation in HFrEF. In-hospital mortality was 3.4% in HFrEF, 2.1% in HFmrEF and 2.2% in HFpEF. Intravenous diuretic (∼80%) and nitrate (∼15%) use was similar but inotrope use greater in HFrEF (16%, vs. HFmrEF 7.4% vs. HFpEF 5.3%). Weight loss and estimated glomerular filtration rate improvement were greater in HFrEF, whereas reduction in natriuretic peptides was similar. Over 1 year post-discharge, events per 100 patient-years (95% confidence interval) in HFrEF versus HFmrEF versus HFpEF were: all-cause death 22 (20-24) versus 17 (14-20) versus 17 (15-20); cardiovascular (CV) death 12 (10-13) versus 8.6 (6.6-11) versus 8.4 (6.9-10); non-CV death 2.4 (1.8-3.1) versus 3.3 (2.1-4.8) versus 4.5 (3.5-5.9); all-cause hospitalization 48 (45-51) versus 35 (31-40) versus 42 (39-46); HF hospitalization 29 (27-32) versus 19 (16-22) versus 17 (15-20); and non-CV hospitalization 7.7 (6.6-8.9) versus 9.6 (7.5-12) versus 15 (13-17)., Conclusion: In AHF, HFrEF is more severe and has greater in-hospital mortality. Post-discharge, HFrEF has greater CV risk, HFpEF greater non-CV risk, and HFmrEF lower overall risk., (© 2021 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background: Aortic stenosis (AS) is the most common acquired valvular disease. There are two methods of interventional treatment: surgical aortic valve replacement (SAVR) and transcatheter aortic valve implantation (TAVI). The choice between SAVR and TAVI depends on the assessment of individual perioperative risk and long-term treatment outcomes. It is essential to identify factors that may influence the outcomes of the treatment to minimize their negative effects., Aims: The study aimed to identify the most important risk factor which affects treatment outcomes in patients with AS undergoing SAVR/TAVI., Methods: This study reviewed retrospectively patients with AS who underwent SAVR or TAVI. The primary outcomes included incidences of major adverse cardiovascular events (MACE) defined as cardiovascular death, stroke, and hospitalization for cardiovascular issues assessed over a one-year follow-up period. An occurrence of postprocedural AKI (acute kidney injury) was identified as an independent predictor of MACE., Results: The study included 78 patients, with the same number of subjects in each group (SAVR/TAVI [n = 39]). Twenty-nine patients developed AKI. It was similar in both groups (SAVR [n = 15]; TAVR [n = 14]). In the SAVR group, 13 (33%) patients developed at least one MACE compared to 5 (13%) patients in the TAVI group. AKI and the type of procedure (SAVR) were shown to be significantly and independently associated with the development of MACE (P = 0.01 and P = 0.03, respectively) as shown in the Cox multivariable regression model., Conclusions: Our study demonstrated that AKI is the strongest predictor of major adverse cardiovascular events after using both methods of aortic valve replacement (SAVR/TAVI).

Introduction: Optimal medical therapy (OMT) is the cornerstone of treatment for stable coronary disease with the ISCHEMIA trial showing similar outcomes using OMT with or without an initial invasive approach. Objectives: To describe OMT goal attainment in Polish ISCHEMIA participants compared with other countries. Patients and methods: Among 5179 trial participants, 333 were randomized in Poland. The median follow-up was 3.2 years. OMT targets were: not smoking, high-intensity statin therapy, low-density lipoprotein cholesterol (LDL-C) of less than 70 mg/dl, systolic blood pressure of less than 140 mm Hg, aspirin therapy, and ACEI / ARB, and β-blocker therapy if indicated. Results: Compared with 36 other countries, at randomization, patients in Poland were older (67 [62–75] y vs 65 [58–71] y); P <⁠0.001), more often female (30% vs 22%; P = 0.002), with a longer history of angina (3 [1–9] y vs 1 [0–3] y; P <⁠0.001), and there were more cases of prior myocardial infarction (32% vs 18%; P <⁠0.01) and revascularization (PCI, 40% vs 19%; CABG, 11% vs 3%; P <⁠0.001 for both). The number of OMT goals attained increased from baseline to follow-up visits (5 [4–5] vs 6 [5–6]; P <⁠0.001) in Poland and other countries alike (P = 0.89 vs P = 0.14). In Poland, significant improvements were achieved regarding high-intensity statin therapy (27% vs 50%), LDL-C <⁠70 mg/dl (29% vs 65%), and systolic blood pressure of less than 140 mm Hg (63% vs 81%) (P <⁠0.001 for all), whereas not-smoking (89% vs 89%), aspirin (90% vs 88%), ACEI / ARB (93% vs 95%), and β-blocker therapy (94% vs 90%) remained high. Conclusions: With regular surveillance and contemporary medical therapy, high OMT goal attainment was achievable among the participants of the ISCHEMIA trial in Poland relative to other countries. There is still room for improvement in LDL-C and blood pressure management.

Aims: In heart failure with reduced ejection fraction (HFrEF), there is an 'obesity paradox', where survival is better in patients with a higher body mass index (BMI) and weight loss is associated with worse outcomes. We examined the effect of a sodium-glucose co-transporter 2 inhibitor according to baseline BMI in the Dapagliflozin And Prevention of Adverse-outcomes in Heart Failure trial (DAPA-HF)., Methods and Results: Body mass index was examined using standard categories, i.e. underweight (<18.5 kg/m 2 ); normal weight (18.5-24.9 kg/m 2 ); overweight (25.0-29.9 kg/m 2 ); obesity class I (30.0-34.9 kg/m 2 ); obesity class II (35.0-39.9 kg/m 2 ); and obesity class III (≥40 kg/m 2 ). The primary outcome in DAPA-HF was the composite of worsening heart failure or cardiovascular death. Overall, 1348 patients (28.4%) were under/normal-weight, 1722 (36.3%) overweight, 1013 (21.4%) obesity class I and 659 (13.9%) obesity class II/III. The unadjusted hazard ratio (95% confidence interval) for the primary outcome with obesity class 1, the lowest risk group, as reference was: under/normal-weight 1.41 (1.16-1.71), overweight 1.18 (0.97-1.42), obesity class II/III 1.37 (1.10-1.72). Patients with class I obesity were also at lowest risk of death. The effect of dapagliflozin on the primary outcome and other outcomes did not vary by baseline BMI, e.g. hazard ratio for primary outcome: under/normal-weight 0.74 (0.58-0.94), overweight 0.81 (0.65-1.02), obesity class I 0.68 (0.50-0.92), obesity class II/III 0.71 (0.51-1.00) (P-value for interaction = 0.79). The mean decrease in weight at 8 months with dapagliflozin was 0.9 (0.7-1.1) kg (P < 0.001)., Conclusion: We confirmed an 'obesity survival paradox' in HFrEF. We showed that dapagliflozin was beneficial across the wide range of BMI studied., Clinical Trial Registration: ClinicalTrials.gov NCT03036124., (© 2021 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)