<div><h4>Guideline directed medical therapy in severe heart failure with reduced ejection fraction: an analysis from the HELP-HF Registry.</h4><i>Tomasoni D, Pagnesi M, Colombo G, Chiarito M, ... Savarese G, Metra M</i><br /><b>Background</b><br />Persistent symptoms despite guideline directed medical therapy (GDMT) and poor tolerance of GDMT are hallmarks of patients with advanced heart failure (HF) with reduced ejection fraction (HFrEF). However, real-world data on GDMT use, dose, and prognostic implications are lacking.<br /><b>Methods and results</b><br />We included 699 consecutive patients with HFrEF and at least one \"I NEED HELP\" marker for advanced HF enrolled in a multicentre registry. Beta-blockers (BB) were administered to 574 (82%) patients, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers or angiotensin receptor neprilysin inhibitors (ACEi/ARB/ARNI) were administered to 381 (55%) patients and 416 (60%) received mineralocorticoid receptor antagonist (MRA). Overall, ≥50% of target doses were reached in 41%, 22% and 56% of the patients on BB, ACEi/ARB/ARNI and MRA, respectively. Hypotension, bradycardia, kidney dysfunction and hyperkalaemia were the main causes of underprescription and/or underdosing, but up to a half of the patients did not receive target doses for unknown causes (51%, 41% and 55% for BB, ACEi/ARB/ARNI and MRA, respectively).The proportions of patients receiving BB and ACEi/ARB/ARNI were lower among those fulfilling the 2018 HFA-ESC criteria for advanced HF. Treatment with BB and ACEi/ARB/ARNI were associated with a lower risk of death or HF hospitalizations (adjusted hazard ratio [HR], 0.63, 95% confidence interval [CI], 0.48-0.84, and HR 0.74, 95%CI 0.58-0.95, respectively).<br /><b>Conclusions</b><br />In a large, real-world, contemporary cohort of patients with severe HFrEF, with at least one marker for advanced HF, prescription and uptitration of GDMT remained limited. A significant proportion of patients were under-treated due to unknown reasons suggesting a potential role of clinical inertia either by the prescribing healthcare professional or by the patient. Treatment with BB and ACEi/ARB/ARNI was associated with lower mortality/morbidity. This article is protected by copyright. All rights reserved.<br /><br />This article is protected by copyright. All rights reserved.<br /><br /><small>Eur J Heart Fail: 07 Nov 2023; epub ahead of print</small></div>

<div><h4>Sacubitril/valsartan compared to ramipril in high-risk post myocardial infarction patients stratified according use of mineralocorticoid receptor antagonists: Insight from PARADISE MI trial.</h4><i>Schou M, Claggett B, Miao ZM, Fernandez A, ... Pfeffer MA, Køber L</i><br /><b>Background</b><br />It is unknown whether safety and clinical endpoints by use of sacubitril/valsartan (ARNI) is affected by Mineralocorticoid receptor antagonists (MRA) in high-risk myocardial infarction (MI) patients.<br /><b>Purpose</b><br />To examine whether MRA modifies safety and clinical endpoints by use of sacubitril/valsartan in patients with a MI and left ventricular systolic dysfunction (LVSD) and/or pulmonary congestion.<br /><b>Methods</b><br />Patients (N=5661) included in the PARADISE MI Trial (Prospective ARNI vs. ACE inhibitor trial to DetermIne Superiority in reducing heart failure (HF) Events after MI) were stratified according to MRA. Primary outcomes in this substudy were worsening HF or cardiovascular death. Safety was defined as symptomatic hypotension, hyperkalemia > 5.5 mmol/L or permanent drug discontinuation.<br /><b>Results</b><br />2338 patients (41%) were treated with MRA. Safety of ARNI compared to ramipril was not altered significantly by +/-MRA, and both groups had similar increase in symptomatic hypotension with ARNI. In patients taking MRA, the risk of hyperkalemia or permanent drug discontinuation was not significantly altered by ARNI (P> 0.05 for all comparisons). The effect of ARNI compared with ramipril was similar in those who were and were not taking MRA: hazard ratio<sub>MRA</sub> : (95% confidence interval [CI]): 0.96 (0.77, 1.19) versus (HR<sub>MRA-</sub> 0.87 (95% CI: 0.71, 1.05), respectively, for the primary endpoint (p value for interaction = 0.51) (CEC adjudicated); similar findings were observed if investigator reported endpoints were evaluated (P = 0.61 for interaction).<br /><b>Conclusions</b><br />Use of a MRA did not modify safety or clinical endpoints related to initiation of ARNI compared to ramipril in the post MI setting in patients with LVSD and/or congestion. This article is protected by copyright. All rights reserved.<br /><br />This article is protected by copyright. All rights reserved.<br /><br /><small>Eur J Heart Fail: 06 Nov 2023; epub ahead of print</small></div>

<div><h4>The short-term effects of sacubitril/valsartan therapy on myocardial oxygen consumption and energetic efficiency of cardiac work in heart failure with reduced ejection fraction. A randomized controlled study.</h4><i>Nesterov SV, Räty J, Nammas W, Maaniitty T, ... Saraste A, Knuuti J</i><br /><b>Aims</b><br />We sought to evaluate the mechanism of angiotensin-converting enzyme inhibitor (ARNI) sacubitril/valsartan therapy and compare it with a valsartan-only control group in HFrEF patients.<br /><b>Methods and results</b><br />The study was a phase IV, prospective, randomized, double-blind, parallel-group study in patients with NYHA class II-III heart failure (HF) and left ventricular (LV) ejection fraction (EF) ≤35%. During a 6-week run-in period, all patients received valsartan therapy, which was up-titrated to the highest tolerated dose level (80 mg BID or 160 mg BID) and then randomized to either valsartan or sacubitril/valsartan. Myocardial oxygen consumption, energetic efficiency of cardiac work, cardiac and systemic hemodynamics were quantified using echocardiography and <sup>11</sup> C-acetate PET before and after 6 weeks of therapy (on stable dose) in 55 patients (ARNI group-27 patients, age 63±10 years, EF 29.2±10.4%, and valsartan only control group-28 patients, age 64±8 years, EF 29.0±7.3%, all ns.) The energetic efficiency of cardiac work remained unchanged in both treatment arms. However, both the diastolic (-4.5 mm Hg; p=0.026) and systolic blood pressure (-9.8 mm Hg; p=0.0007), myocardial perfusion (-0.054 mL/g/min; p=0.045), and LV mechanical work (-296; p=0.038) decreased significantly in the ARNI group compared with the control group. Although myocardial oxygen consumption decreased in the ARNI group (-5.4%) compared with the run-in period and remained unchanged in the control group (+0.5%), the between treatment group difference was not significant (p=0.088).<br /><b>Conclusions</b><br />We found no differences in the energetic efficiency of cardiac work between ARNI and valsartan-only groups in HFrEF patients. However, ARNI appears to have hemodynamic and cardiac mechanical effects over valsartan in patients with HF. (EudraCT 2017-002113-64) This article is protected by copyright. All rights reserved.<br /><br />This article is protected by copyright. All rights reserved.<br /><br /><small>Eur J Heart Fail: 31 Oct 2023; epub ahead of print</small></div>

<div><h4>Long-term outcome after upgrade to cardiac resynchronization therapy: A propensity score-matched analysis.</h4><i>Trenson S, Voros G, Martens P, Ingelaere S, ... Winnik S, Vandenberk B</i><br /><b>Background</b><br />Cardiac resynchronization therapy (CRT) is a cornerstone in the management of chronic heart failure in patients with a broad or paced QRS. However, data on long-term outcome after upgrade to CRT are scarce.<br /><b>Methods</b><br />International, multicenter retrospective registry including 2275 patients who underwent a de novo or upgrade CRT implantation and mean follow-up of 3.6±2.7 years. The primary composite endpoint included all-cause mortality, heart transplantation or ventricular assist device implantation. The secondary endpoint was first heart failure admission. Multivariable Cox regression and propensity score matched (PSM) analyses were performed.<br /><b>Results</b><br />Patients who underwent CRT upgrade (n=605, 26.6%) were less likely female (19.7% vs 28.8%, p<0.001), more often had ischemic cardiomyopathy (49.8% vs 40.2%, p<0.001), and had worse renal function (median eGFR 50.3 mL/m<sup>2</sup> (35.8-69.5) vs 59.9 mL/m<sup>2</sup> (43.0-76.5), p<0.001). The incidence rate of the composite endpoint was 10.8%/year after CRT upgrade vs. 7.1%/year for de novo implantations (p<0.001). PSM for the primary endpoint resulted in 488 pairs. After PSM, upgrade to CRT was associated with a higher chance to reach the composite endpoint (multivariable HR 1.35, 95% CI 1.08-1.70), for both upgrade from pacemaker (multivariable HR 1.33, 95% CI 1.03-1.70) and ICD (multivariable HR 1.40, 95% CI 1.01-1.95). PSM for the secondary endpoint resulted in 277 pairs. After PSM, upgrade to CRT was associated with a higher chance for heart failure admission (HR 1.74, 95% CI 1.26-2.41).<br /><b>Conclusion</b><br />In this retrospective analysis, the outcome of patients who underwent upgrades to CRT differed significantly from patients who underwent de novo CRT implantation, particularly for upgrades from ICD. Importantly, this difference in outcome does not imply a causal relation between therapy and outcome but rather a difference between two different patient populations. This article is protected by copyright. All rights reserved.<br /><br />This article is protected by copyright. All rights reserved.<br /><br /><small>Eur J Heart Fail: 31 Oct 2023; epub ahead of print</small></div>

<div><h4>Early changes in renal function during rapid uptitration of guideline directed medical therapy following an admission for acute heart failure.</h4><i>Ter Maaten JM, Mebazaa A, Davison B, Edwards C, ... Cotter G, Voors AA</i><br /><b>Introduction</b><br />In this subgroup analysis of STRONG-HF we explored the association between changes in renal function and efficacy of rapid up-titration of guideline directed medical therapy (GDMT) according to a high intensity care (HIC) strategy.<br /><b>Methods</b><br />In patients randomized to the HIC arm (n = 542), renal function was assessed at baseline and during follow-up visits. We studied the association with clinical characteristics and outcomes of a decrease in estimated glomerular filtration rate (eGFR) at week 1, defined as ≥15% decrease from baseline. Patients in the usual care group (n = 536) were seen at day 90.<br /><b>Results</b><br />The treatment effect of HIC versus usual care was independent of baseline eGFR (P-interaction: 0.4809). A decrease in eGFR within 1 week occurred in 77 (15.5%) patients and was associated with more rales on examination (P = 0.004), and a higher NYHA class at the corresponding visit. Following the decrease in eGFR at 1 week, lower average optimal doses of GDMT were prescribed during follow-up (P = 0.0210) and smaller reductions in NT-proBNP occurred (geometrical mean 0.81 in no eGFR decrease vs 1.12 in GFR decrease, P = 0.0003). The rate of HF readmission or death at 180 days was 12.3% in no eGFR decrease vs. 18.5% in eGFR decrease (P = 0.2274) and HF readmissions were 7.8% vs 16.6% respectively, P = 0.0496.<br /><b>Conclusions</b><br />In the STRONG-HF study, HIC reduced 180-day HF readmission or death regardless of baseline eGFR. An early decrease in eGFR during rapid uptitration of GDMT was associated with more evidence of congestion yet lower doses of GDMT during follow-up. This article is protected by copyright. All rights reserved.<br /><br />This article is protected by copyright. All rights reserved.<br /><br /><small>Eur J Heart Fail: 31 Oct 2023; epub ahead of print</small></div>

<div><h4>Incidence, risk assessment and prevention of sudden cardiac death in cardiomyopathies.</h4><i>Polovina M, Tschöpe C, Rosano G, Metra M, ... Coats AJ, Seferović PM</i><br /><AbstractText>Cardiomyopathies are a significant contributor to cardiovascular morbidity and mortality, mainly due to the development of heart failure and increased risk of sudden cardiac death (SCD). Despite improvement in survival with contemporary treatment, SCD remains an important cause of mortality in cardiomyopathies. It occurs at a rate ranging between 0.15%-0.7% per year (depending on the cardiomyopathy), which significantly surpasses SCD incidence in the age- and sex-matched general population. The risk of SCD is affected by multiple factors including the aetiology, genetic basis, age, sex, physical exertion, the extent of myocardial disease severity, conduction system abnormalities, and electrical instability, as measured by various metrics. Over the past decades, the knowledge on the mechanisms and risk factors for SCD has substantially improved, allowing for a better-informed risk stratification. However, unresolved issues still challenge the guidance of SCD prevention in patients with cardiomyopathies. In this review, we aim to provide an in-depth discussion of the contemporary concepts pertinent to understanding the burden, risk assessment and prevention of SCD in cardiomyopathies (dilated, non-dilated left ventricular, hypertrophic, arrhythmogenic right ventricular, and restrictive). The review first focuses on SCD incidence in cardiomyopathies and then summarises established and emerging risk factors for life-threatening arrhythmias/SCD. Finally, it discusses validated approaches to the risk assessment and evidence-based measures for SCD prevention in cardiomyopathies, pointing to the gaps in evidence and areas of uncertainties that merit future clarification. This article is protected by copyright. All rights reserved.</AbstractText><br /><br />This article is protected by copyright. All rights reserved.<br /><br /><small>Eur J Heart Fail: 31 Oct 2023; epub ahead of print</small></div>

<div><h4>Interaction of Heart Failure and Stroke: A clinical consensus statement of the ESC Council on Stroke, the Heart Failure Association (HFA) and the ESC Working Group on Thrombosis.</h4><i>Doehner W, Böhm M, Boriani G, Christersson C, ... Vilahur G, Rosano G</i><br /><AbstractText>Heart failure (HF) is a major disease in our society that often presents with multiple comorbidities with mutual interaction and aggravation. The comorbidity of HF and stroke is a high risk condition that requires particular attention to ensure early detection of complications, efficient diagnostic workup, close monitoring, and consequent treatment of the patient. The bi-directional interaction between the heart and the brain is inherent in the pathophysiology of HF where HF may be causal for acute cerebral injury, and - in turn - acute cerebral injury via imbalanced neural and neurovegetative control of cardiovascular regulation may induce or aggravate HF. The present document represents the consensus view of the ESC Council on Stroke, the Heart Failure Association and the ESC Working Group on Thrombosis to summarize current insights on pathophysiologic interactions of the heart and the brain in the comorbidity of HF and stroke. Principal aspects of diagnostic workup, pathophysiologic mechanisms, complications clinical management in acute conditions and in long-term care of patients with the comorbidity are presented and state of the art clinical management and current evidence from clinical trials is discussed. Beside the physicians perspective, also the patients values and preferences are taken into account. Interdisciplinary cooperation of cardiologists, stroke specialists, other specialists and primary care physicians is pivotal to ensure optimal treatment in acute events and in continued long-term treatment of these patients. Key consensus statements are presented in a concise overview on mechanistic insights, diagnostic workup, prevention and treatment to inform clinical acute and continued care of patients with the comorbidity of heart failure and stroke.</AbstractText><br /><br />This article is protected by copyright. All rights reserved.<br /><br /><small>Eur J Heart Fail: 31 Oct 2023; epub ahead of print</small></div>

<div><h4>Characteristics and outcomes of patients with atrial versus ventricular secondary tricuspid regurgitation undergoing tricuspid transcatheter edge-to-edge repair - Results from TriValve Registry.</h4><i>Russo G, Badano LP, Adamo M, Alessandrini H, ... Metra M, Taramasso M</i><br /><b>Background</b><br />Secondary or functional tricuspid regurgitation (STR) is the most common phenotype of tricuspid regurgitation (TR) with atrial STR (ASTR) and ventricular STR (VSTR) being recently identified as two distinct entities. Data on tricuspid transcatheter edge-to-edge repair (T-TEER) in patients with STR according to phenotype (i.e. ASTR vs VSTR) are lacking.<br /><b>Objectives</b><br />The aim of this study was to assess characteristics and outcomes of patients with ASTR vs VSTR undergoing T-TEER.<br /><b>Methods</b><br />Patients with STR undergoing T-TEER were selected from the TriValve (Transcatheter Tricuspid Valve Therapies) registry. ASTR was defined by 1) left ventricular ejection fraction ≥50%; 2) atrial fibrillation and 3) systolic pulmonary arterial pressure < 50 mmHg. Patients not matching these criteria were classified as VSTR. Patients with primary TR and cardiac implantable electronic device were excluded. Key end-points included procedural success and survival at follow-up.<br /><b>Results</b><br />Two-hundred-ninety-eight patients were enrolled in the study: 65 (22%) with ASTR and 233 (78%) with VSTR. Procedural success was similar in the two groups (80% vs 83% for ASTR and VSTR, respectively, p = 0.56) and TEER was effective in reducing TR in both groups (from 97% of patients with baseline TR ≥3+ to 23% in ASTR and to 15% in VSTR, all p = 0.001). At 12 months follow-up, survival was significantly higher in ASTR vs VSTR cohort (91% vs 72%, log rank p = 0.02), with VSTR being an independent predictor of mortality at multivariable analysis (hazard ratio 4.75).<br /><b>Conclusions</b><br />In a real-world, multicenter registry, T-TEER was effective in reducing TR grade in both ASTR and VSTR. At 12-months follow-up, ASTR showed better survival than VSTR. This article is protected by copyright. All rights reserved.<br /><br />© 2023 European Society of Cardiology.<br /><br /><small>Eur J Heart Fail: 31 Oct 2023; epub ahead of print</small></div>

<div><h4>Hypotension in heart failure is less harmful if associated with high or increasing doses of heart failure medication: Insights from the Swedish Heart Failure Registry.</h4><i>Girerd N, Coiro S, Benson L, Savarese G, ... Rossignol P, Lund LH</i><br /><b>Background</b><br />Heart failure (HF) medication may reduce blood pressure (BP). Low BP is associated with worse outcomes but how this association is modified by HF medication has not been studied. We evaluated the association between BP and outcomes according to HF medication dose in HF with reduced ejection fraction (HFrEF).<br /><b>Methods</b><br />We studied HFrEF patients from the Swedish HF registry (2000-2018). Associations between systolic BP (SBP) and cardiovascular death and/or HF hospitalization (CVD/HFH) were analyzed according to doses of renin-angiotensin system (RAS) inhibitors, beta-blockers and mineralocorticoid receptor antagonists (MRA).<br /><b>Results</b><br />Among 42 040 patients (median age 74.0), lower baseline SBP was associated with higher risk of CVD/HFH (adjusted HR per 10 mmHg higher SBP: 0.92 [0.92-0.93]), which was less high risk under optimized RAS inhibitors and beta-blockers doses (10% decrease in event rates per 10 mmHg SBP increase in untreated patients versus 7% decrease in patients at maximum dose, both adjusted p < 0.02). Among the 13 761 patients with repeated measurements, 9.9% reported a SBP decrease >10 mmHg when HF medications\' doses were increased, whereas 24.6% reported a SBP decrease >10 mmHg with stable/decreasing doses. Decreasing SBP was associated with higher risk of CVD/HFH in patients with stable (HR = 1.10 [1.04-1.17]) or decreasing (HR = 1.29 [1.18-1.42]) HF medication dose but not in patients with an increase in doses (HR = 0.94 [0.86-1.02]).<br /><b>Conclusions</b><br />The association of lower SBP with higher risk of CVD/HFH is attenuated in patients with optimized HF medication. These results suggest that low or declining SBP should not limit HF medication optimization. This article is protected by copyright. All rights reserved.<br /><br />This article is protected by copyright. All rights reserved.<br /><br /><small>Eur J Heart Fail: 26 Oct 2023; epub ahead of print</small></div>

<div><h4>Predictors of outcome in a contemporary cardiac sarcoidosis population: Role of brain natriuretic peptide, left ventricular function and myocardial inflammation.</h4><i>Kouranos V, Khattar RS, Okafor J, Ahmed R, ... Lüscher TF, Sharma R</i><br /><b>Aims</b><br />Cardiac sarcoidosis (CS) is a potentially fatal condition that varies in its clinical presentation. Here, we describe baseline characteristics at presentation along with prognosis and predictors of outcome in a sizable and deeply phenotyped contemporary cohort of CS patients.<br /><b>Methods and results</b><br />Consecutive CS patients seen at one institution were retrospectively enrolled after undergoing laboratory testing, ECG, echocardiography, cardiac magnetic resonance imaging (CMR) and <sup>18</sup> -Flourodeoxyglucose positron emission tomography (FDG- PET) at baseline. The composite endpoint consisted of all-cause mortality, aborted sudden cardiac death, major ventricular arrhythmic events, heart failure hospitalization and heart transplantation. A total of 319 CS patients were studied (67% male, 55.4±12 years of age). During median follow-up of 2.2 years (range:1 month-11 years), 8% of patients died, while 33% reached the composite endpoint. The annualized mortality rate was 2.7% and the 5-year and 10-year mortality rates were 6.2% and 7.5%, respectively. Multivariate analysis showed serum brain natriuretic peptide (BNP) levels (HR:2.41, 95%CI 1.34-4.31, p=0.003), CMR-LVEF (HR:0.96, 95%CI 0.94-0.98, p<0.0001) and maximum Standardized Uptake Value (SUVmax) of FDG-PET; HR:1.11; 95%CI 1.04-1.19, p=0.001) to be independent predictors of outcome. These findings remained robust for different patient subgroups.<br /><b>Conclusion</b><br />CS is associated with significant morbidity and mortality, particularly in those with cardiac involvement as the first manifestation. Higher BNP levels, lower LVEF and more active myocardial inflammation were independent predictors of outcomes. This article is protected by copyright. All rights reserved.<br /><br />This article is protected by copyright. All rights reserved.<br /><br /><small>Eur J Heart Fail: 25 Oct 2023; epub ahead of print</small></div>

<div><h4>Qiliqiangxin: a Multifaceted Holistic Treatment for Heart Failure or a Pharmacological Probe for the Identification of Cardioprotective Mechanisms?</h4><i>Packer M</i><br /><AbstractText>The active ingredients in many traditional Chinese medicines are isoprene oligomers with a diterpenoid or triterpenoid structure, which exert cardiovascular effects by signaling through nutrient surplus and nutrient deprivation pathways. Qiliqiangxin (QLQX) is a commercial formulation of 11 different plant ingredients, whose active compounds include astragaloside IV, tanshione IIA, ginsenosides (Rb1, Rg1 and Re) and periplocymarin. In the QUEST Trial, QLQX reduced the combined risk of cardiovascular death or heart failure hospitalization (hazard ratio 0.78 [95% CI 0.68-0.90]), based on 859 events in 3119 patients over a median of 18.2 months; the benefits were seen in patients taking foundational drugs except for SGLT2 inhibitors. Numerous experimental studies of QLQX in diverse cardiac injuries have yielded highly consistent findings. In marked abrupt cardiac injury, QLQX mitigated cardiac injury by upregulating nutrient surplus signaling through the PI3K/Akt/mTOR/HIF-1α/NRF2 pathway; the benefits of QLQX were abrogated by suppression of PI3K, Akt, mTOR, HIF-1α or NRF2. In contrast, in prolonged measured cardiac stress (as in chronic heart failure), QLQX ameliorated oxidative stress, maladaptive hypertrophy, cardiomyocyte apoptosis, and proinflammatory and profibrotic pathways, while enhancing mitochondrial health and promoting glucose and fatty acid oxidation and ATP production. These effects are achieved by an action of QLQX to upregulate nutrient deprivation signaling through SIRT1/AMPK/PGC-1α and enhanced autophagic flux. In particular, QLQX appears to enhance the interaction of PGC-1α with PPARα, possibly by direct binding to RXRα; silencing of SIRT1, PGC-1α and RXRα abrogated the favorable effects of QLQX in the heart. Since PGC-1α/RXRα is also a downstream effector of Akt/mTOR signaling, the actions of QLQX on PGC-1α/RXRα may explain its favorable effects in both acute and chronic stress. Intriguingly, the individual ingredients in QLQX - astragaloside IV, ginsenosides, and tanshione IIA - share QLQX\'s effects on PGC-1α/RXRα/PPARα signaling. QXQL also contains periplocymarin, a cardiac glycoside that inhibits Na+-K+-ATPase. Taken collectively, these observations support a conceptual framework for understanding the mechanism of action for QLQX in heart failure. The high likelihood of overlap in the mechanism of action of QLQX and SGLT2 inhibitors requires additional experimental studies and clinical trials. This article is protected by copyright. All rights reserved.</AbstractText><br /><br />This article is protected by copyright. All rights reserved.<br /><br /><small>Eur J Heart Fail: 25 Oct 2023; epub ahead of print</small></div>

<div><h4>Comprehensive Vasodilation in Women with Acute Heart Failure: Novel Insights from the GALACTIC randomized controlled trial.</h4><i>Wussler D, Belkin M, Maeder MT, Walter J, ... Mueller C, GALACTIC Investigators</i><br /><b>Background:</b><br/>and aims</b><br />Sex-specific differences in acute heart failure (AHF) are both relevant and underappreciated. Therefore, it is crucial to evaluate the risk/benefit ratio and the implementation of novel AHF therapies in women and men separately.<br /><b>Methods and results</b><br />We performed a predefined sex-specific analysis in AHF patients randomized to a strategy of early intensive and sustained vasodilation versus usual care in an international, multicenter, open-label, blinded-end-point trial. Inclusion criteria were AHF with increased plasma concentrations of natriuretic peptides, systolic blood pressure ≥ 100 mmHg, and plan for treatment in a general ward. Among 781 eligible patients, 288 (37%) were women. Women were older (median 83 versus 76 years), had a lower body weight (median 64.5 versus 77.6 kg) and lower estimated glomerular filtration rate (median 48 versus 54 mL/min per 1,73 m<sup>2</sup> ). The primary endpoint, a composite of all-cause mortality or rehospitalization for AHF at 180 days, showed a significant interaction of treatment strategy and sex (p for interaction = 0.03; hazard ratio adjusted for female sex 1.62 [95% CI, 1.05-2.50]; p = 0.03). The combined endpoint occurred in 53 women (38%) in the intervention group and in 35 (24%) in the usual care group. The implementation of rapid up-titration of renin-angiotensin-aldosterone system (RAAS) inhibitors was less successful in women versus men in the overall cohort and in patients with heart failure with reduced ejection fraction (median discharge % target dose in patients randomized to intervention: 50% in women vs. 75% in men, respectively).<br /><b>Conclusion</b><br />Rapid up-titration of RAAS inhibitors was less successfully implemented in women possibly explaining their higher rate of all-cause mortality and rehospitalization for AHF. This article is protected by copyright. All rights reserved.<br /><br />This article is protected by copyright. All rights reserved.<br /><br /><small>Eur J Heart Fail: 23 Oct 2023; epub ahead of print</small></div>

<div><h4>Exercise-based cardiac rehabilitation for adults with heart failure - 2023 Cochrane systematic review and meta-analysis.</h4><i>Molloy CD, Long L, Mordi IR, Bridges C, ... Singh SJ, Taylor RS</i><br /><b>Background:</b><br/>and aims</b><br />Despite strong evidence, access to exercise-based cardiac rehabilitation (ExCR) remains low across global healthcare systems. We provide a contemporary update of the Cochrane review randomised trial evidence for ExCR for adults with heart failure (HF) and compare different delivery modes: centre-based, home-based (including digital support), and both (hybrid).<br /><b>Methods</b><br />Databases, bibliographies of previous systematic reviews and included trials, and trials registers were searched with no language restrictions. Randomised controlled trials, recruiting adults with HF, assigned to either ExCR or a no-exercise control group, with follow-up ≥6-months were included. Two review authors independently screened titles for inclusion, extracted trial and patient characteristics, outcome data, and assessed risk of bias. Outcomes of mortality, hospitalisation, and health-related quality of life (HRQoL) were pooled across trials using meta-analysis at short-term (≤12 months) and long-term follow up (> 12 months) and stratified by delivery mode.<br /><b>Results</b><br />60 trials (8,728 participants) were included. In the short-term, compared to control, ExCR did not impact all-cause mortality (relative risk (RR): 0.93; 95% confidence interval (95% CI): 0.71 to 1.21), reduced all-cause hospitalisation (RR: 0.69; 95% CI: 0.56 to 0.86, number needed to treat: 13, 95% CI: 9 to 22), and was associated with a clinically important improvement in HRQoL measured by the Minnesota Living with Heart Failure Questionnaire (MLWHF) overall score (mean difference: -7.39; 95% CI: -10.30 to -4.47). Improvements in outcomes with ExCR was seen across centre, home (including digitally supported), and hybrid settings. A similar pattern of results was seen in the long-term (mortality: RR 0.87, 95% CI: 0.72 to 1.04; all-cause hospitalisation: RR 0.84, 95% CI: 0.70 to 1.01, MLWHF: -9.59, 95% CI: -17.48 to -1.50).<br /><b>Conclusions</b><br />To improve global suboptimal levels of uptake for HF patients, global healthcare systems need to routinely recommend ExCR and offer a choice of mode of delivery, dependent on an individual patient\'s level of risk and complexity. This article is protected by copyright. All rights reserved.<br /><br />This article is protected by copyright. All rights reserved.<br /><br /><small>Eur J Heart Fail: 18 Oct 2023; epub ahead of print</small></div>

<div><h4>Outcomes at one year in women with peripartum cardiomyopathy: findings from the ESC EORP PPCM Registry.</h4><i>Jackson AM, Bauersachs J, Petrie MC, van der Meer P, ... Sliwa K, EurObservational Research Programme in conjunction with the Heart Failure Association of the European Society of Cardiology Study Group on Peripartum Cardiomyopathy</i><br /><b>Aims</b><br />There are few prospective reports of 1-year outcomes for women with peripartum cardiomyopathy (PPCM). We report findings from the European Society of Cardiology EURObservational Research Programme PPCM Registry.<br /><b>Methods and results</b><br />The registry enrolled women from 51 countries from 2012-2018. Eligibility included: 1) a peripartum state, 2) signs or symptoms of heart failure, 3) LV ejection fraction ≤45%, 4) exclusion of alternative causes of heart failure. We report mortality, thromboembolism, stroke, re-hospitalization, LV recovery and remodelling at 1 year. Differences between regions were compared. One-year mortality data were available in 535 (71%) women and follow-up differed across regions. At 1 year, death from any cause occurred in 8.4% of women, with regional variation (Europe 4.9%, Africa 6.5%, Asia-Pacific 9.2%, Middle East 18.9%, p < 0.001). The frequencies of thromboembolism and stroke were 6.3% and 2.5%, respectively, and were similar across regions. A total of 14.0% of women had at least one re-hospitalization and 3.5% had recurrent re-hospitalizations (i.e. two or more). Overall, 66.1% of women had recovery of LV function (22% between 6 months and 1 year), with a mean LVEF increase from baseline of 21.2% [±13.6]). Recovery occurred most frequently in Asia-Pacific (77.5%) and least frequently in the Middle East (32.7%). There were significant regional differences in the use of heart failure pharmacotherapies.<br /><b>Conclusions</b><br />Approximately 1 in 12 women with PPCM had died by 1 year and thromboembolism and stroke occurred in 6.3% and 2.5%, respectively. Around 1 in 7 women had been re-hospitalized and, in 1 in 3, LV recovery had not occurred. PPCM is associated with substantial mortality and morbidity globally.<br /><br />This article is protected by copyright. All rights reserved.<br /><br /><small>Eur J Heart Fail: 12 Oct 2023; epub ahead of print</small></div>

<div><h4>Clinical characteristics and prognosis of patients with isolated cardiac sarcoidosis: Insights from the ILLUMINATE-CS study.</h4><i>Maeda D, Matsue Y, Dotare T, Sunayama T, ... Baba Y, Minamino T</i><br /><b>Aim</b><br />Data on the clinical features and prognosis of patients with isolated cardiac sarcoidosis (iCS) are limited. This study evaluated the clinical characteristics and prognostic impact of iCS.<br /><b>Methods and results</b><br />This was a secondary analysis of the ILLUMINATE-CS study, a multicentre, retrospective registry investigating the clinical characteristics and prognosis of CS. iCS was diagnosed according to the 2016 Japanese Circulation Society (JCS) guidelines. Clinical characteristics and prognosis were compared between patients with iCS and systemic CS (sCS). The primary outcome was a combined endpoint of all-cause death, hospitalisation for heart failure, or fatal ventricular arrhythmia events. Among 475 patients with CS (mean age, 62.0 ± 10.9 years; female ratio, 59%) diagnosed by the JCS guidelines, 119 (25.1%) were diagnosed with iCS. Patients with iCS had a higher prevalence of a history of atrial fibrillation or hospitalisation for heart failure, or lower left ventricular ejection fraction than those with sCS. During a median follow-up of 42.3 (interquartile range, 22.8-72.5) months, 141 primary outcomes (29.7%) occurred. Cox proportional hazard analysis revealed that iCS was a significant risk factor for the primary outcome in the unadjusted model (hazard ratio [HR], 1.62; 95% confidence interval [CI], 1.12-2.34; P=0.011). However, this association was not retained after adjustment for other covariates (adjusted HR, 1.27; 95% CI, 0.86-1.88; P=0.226).<br /><b>Conclusions</b><br />Patients with iCS had more impaired cardiovascular function at the time of diagnosis than those with sCS. However, iCS was not independently associated with poor prognosis after adjustment for prognostic factors. This article is protected by copyright. All rights reserved.<br /><br />This article is protected by copyright. All rights reserved.<br /><br /><small>Eur J Heart Fail: 12 Oct 2023; epub ahead of print</small></div>

<div><h4>The Different Risk of New-onset, Chronic, Worsening, and Advanced Heart Failure A Systematic Review and Meta-Regression Analysis.</h4><i>Shakoor A, Abou Kamar S, Malgie J, Kardys I, ... van der Boon RMA, Brugts JJ</i><br /><b>Background:</b><br/>and aims</b><br />Heart failure (HF) is a chronic and progressive syndrome associated with a poor prognosis. While it may seem intuitive that the risk of adverse outcomes varies across the different stages of HF, an overview of these risks is lacking. This study aims to determine the risk of all-cause mortality and HF hospitalizations associated with new-onset HF, chronic HF (CHF), worsening HF (WHF), and advanced HF (adv. HF).<br /><b>Methods</b><br />We performed a systematic review of observational studies from 2012 to 2022 using five different databases. The primary outcomes were 30-day and one-year all-cause mortality, as well as one-year HF hospitalization. Studies were pooled using random effects meta-analysis, and mixed-effects meta-regression was used to compare the different HF groups.<br /><b>Results</b><br />Among the 15.759 studies screened, 66 were included representing 862.046 HF patients. Pooled 30-day mortality rates did not reveal a significant distinction between hospital-admitted patients, with rates of 10.13% for new-onset HF and 8.11% for WHF (p = 0.10). However, the one-year mortality risk differed and increased stepwise from CHF to adv. HF, with a rate of 8.47% (95% CI 7.24-9.89) for CHF, 21.15% (95% CI 17.78-24.95) for new-onset HF, 26.84% (95% CI 23.74-30.19) for WHF, and 29.74% (95% CI 24.15-36.10) for adv HF. Readmission rates for HF at one year followed a similar trend.<br /><b>Conclusions</b><br />Our meta-analysis of observational studies confirms the different risk for adverse outcomes across the distinct HF stages. Moreover, it emphasizes the negative prognostic value of WHF as the first progressive stage from CHF towards adv. HF. This article is protected by copyright. All rights reserved.<br /><br />This article is protected by copyright. All rights reserved.<br /><br /><small>Eur J Heart Fail: 12 Oct 2023; epub ahead of print</small></div>

<div><h4>Safety of Continuing Mineralocorticoid Receptor Antagonists Treatment in Patients with Heart Failure with Reduced Ejection Fraction and Severe Kidney Disease: Data from Swedish Heart Failure Registry.</h4><i>Guidetti F, Lund LH, Benson L, Hage C, ... Braun OÖ, Savarese G</i><br /><b>Aims</b><br />Mineralocorticoid receptor antagonists (MRAs) improve outcomes in heart failure with reduced ejection fraction (HFrEF) but remain underused and are often discontinued especially in patients with chronic kidney disease (CKD) due to concerns on renal safety. Therefore, in a real-world HFrEF population we investigated the safety of MRAs use, in terms of risk of renal events, any mortality and any hospitalization, across the estimated glomerular filtration rate (eGFR) spectrum including severe CKD.<br /><b>Methods and results</b><br />We analyzed patients with HFrEF (EF < 40%), not on dialysis, from the Swedish Heart Failure Registry. We performed multivariable logistic regression models to investigate patient characteristics independently associated with MRA use, and univariable and multivariable Cox regression models to assess the associations between MRA use and outcomes. Of 33 942 patients, 17 489 (51%) received MRA, 32%, 45%, 54%, 54% with eGFR<30, 30-44, 45-59 or ≥ 60 mL/min/1.73m<sup>2</sup> , respectively. An eGFR ≥60 mL/min/1.73m<sup>2</sup> and patient characteristics linked with more severe HF were independently associated with more likely MRA-use. In multivariable analyses, MRA-use was consistently not associated with a higher risk of renal events (i.e., composite of dialysis/renal death/hospitalization for renal failure or hyperkalemia) [hazard ratio (HR) 1.04, 95% confidence interval (CI) 0.98-1.10], all-cause death (HR 1.02, 95% CI 0.97-1.08) as well as of all-cause hospitalization (HR 0.99, 95% CI 0.95-1.02) across the eGFR spectrum including also severe CKD.<br /><b>Conclusions</b><br />The use of MRAs in patients with HFrEF decreased with worse renal function; however their safety profile was demonstrated to be consistent across the entire eGFR spectrum. This article is protected by copyright. All rights reserved.<br /><br />© 2023 European Society of Cardiology.<br /><br /><small>Eur J Heart Fail: 05 Oct 2023; epub ahead of print</small></div>

<div><h4>Impact of COVID-19 in Patients with Heart Failure with Mildly Reduced or Preserved Ejection Fraction Enrolled in the DELIVER Trial.</h4><i>Bhatt AS, Kosiborod MN, Claggett BL, Miao ZM, ... McMurray JJV, Solomon SD</i><br /><b>Introduction</b><br />COVID-19 may affect clinical risk in patients with heart failure. DELIVER began before and was conducted during the COVID-19 pandemic.<br /><b>Objective</b><br />We evaluated the association between COVID-19 and outcomes among DELIVER participants.<br /><b>Methods</b><br />Participants with chronic 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 (1) incidence of COVID-19, (2) event rates before/during the pandemic, and (3) risks of death after diagnosis compared to death in participants without COVID-19. Further, we performed a sensitivity analysis assessing treatment effects censored at pandemic onset.<br /><b>Results</b><br />Of 6263 participants, 589 (9.4%) developed COVID-19, of whom 307 (52%) required/prolonged hospitalization. 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% CI:48.0 to 65.6) vs. 6.4 (95% CI:6.0-6.8)/100-participant-years among trial participants with versus without COVID-19 (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 to 3.33) than all trial participants from randomization, with censoring of participants who developed COVID-19 at the time of diagnosis. Dapagliflozin reduced the CV 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 DKA or major hypoglycemic events within 30-days of COVID-19.<br /><b>Conclusion</b><br />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 event had a high early residual risk. This article is protected by copyright. All rights reserved.<br /><br />This article is protected by copyright. All rights reserved.<br /><br /><small>Eur J Heart Fail: 28 Sep 2023; epub ahead of print</small></div>

<div><h4>Calcium channel blocker and outcomes in patients with heart failure and mildly reduced and preserved ejection fraction.</h4><i>Matsumoto S, Kondo T, Yang M, Campbell RT, ... Jhund PS, McMurray JJV</i><br /><b>Aims</b><br />Patients with heart failure (HF) and mildly reduced ejection fraction (HFmrEF) and preserved ejection fraction (HFpEF) are often treated with calcium channel blockers (CCBs) although the safety of CCBs in these patients is uncertain. To investigate the association between CCB and clinical outcomes in patients with HFmrEF/HFpEF; CCBs were examined overall, as well as by subtype (dihydropyridine and non-dihydropyridine).<br /><b>Methods and results</b><br />We pooled individual patient data from four large HFpEF/HFmrEF trials. The association between CCB use and outcomes was assessed. Among the 16,954 patients included, the mean left ventricular ejection fraction (LVEF) was 56.8%, and 13,402 (79.0%) had HFpEF (LVEF ≥50%). Overall, 5,874 patients (34.6%) received a CCB (87.6% dihydropyridines). Overall, the risks of death and HF hospitalization were not higher in patients treated with a CCB, particularly dihydropyridines. The risk of pump failure death was significantly lower (HR: 0.76, 95% CI: 0.60-0.96), while the risk of stroke was higher (HR: 1.26, 95% CI: 1.06-1.50) in patients treated with a CCB compared to those not. These risks remained different in patients treated and not treated with a CCB after adjustment for other prognostic variables. Although the majority of patients were treated with dihydropyridine CCBs, the pattern of outcomes was broadly similar for both dihydropyridine and non-dihydropyridine CCBs.<br /><b>Conclusion</b><br />Although this is an observational analysis of non-randomized treatment, there was no suggestion that CCBs were associated with worse HF outcomes. Indeed, CCB use was associated with a lower incidence of pump failure death. This article is protected by copyright. All rights reserved.<br /><br />This article is protected by copyright. All rights reserved.<br /><br /><small>Eur J Heart Fail: 28 Sep 2023; epub ahead of print</small></div>

<div><h4>Phenotype, outcomes and natural history of early-stage non-ischaemic cardiomyopathy.</h4><i>Hammersley DJ, Jones RE, Owen R, Mach L, ... Halliday BP, Prasad SK</i><br /><b>Aims</b><br />To characterise the phenotype, clinical outcomes and rate of disease progression in patients with early-stage non-ischaemic cardiomyopathy (early-NICM).<br /><b>Methods and results</b><br />We conducted a prospective observational cohort study of patients with early-NICM assessed by late-gadolinium-enhancement cardiovascular magnetic resonance. Cases were classified into the following subgroups: isolated left ventricular dilation (early-NICM H-/D+), non-dilated left ventricular cardiomyopathy (early-NICM H+/D-) or early dilated cardiomyopathy (early-NICM H+/D+). Clinical follow-up for major adverse cardiovascular events (MACE) included non-fatal life-threatening arrhythmia, unplanned cardiovascular hospitalisation or cardiovascular death. A subset of patients (n=119) underwent a second CMR to assess changes in cardiac structure and function. Of 254 patients with early-NICM (median age 46 years [interquartile range 36-58], 94 [37%] women, median LVEF 55% [52-59]), myocardial fibrosis was present in 65 (26%). There was no difference in the prevalence of fibrosis between subgroups (p=0.90), however fibrosis mass was lowest in early-NICM H-/D+, higher in early-NICM H+/D- and highest in early-NICM H+/D+ (p=0.03). Over a median follow-up of 7.9 (5.5-10.0) years, 28 patients (11%) experienced MACE. Non-sustained ventricular tachycardia (hazard ratio [HR] 5.1, 95% confidence interval [CI] 2.36-11.00, p<0.001), myocardial fibrosis (HR 3.77, 95% CI 1.73-8.20, p<0.001) and diabetes mellitus (HR 5.12, 95% CI 1.73-15.18, p=0.003) were associated with MACE in a multivariable model. Only 8% of patients progressed from early-NICM to DCM with LVEF <50% over a median of 16 (11-34) months.<br /><b>Conclusion</b><br />Early-NICM is not benign. Fibrosis develops early in the phenotypic course. In-depth characterisation enhances risk stratification and might aid clinical management. This article is protected by copyright. All rights reserved.<br /><br />This article is protected by copyright. All rights reserved.<br /><br /><small>Eur J Heart Fail: 20 Sep 2023; epub ahead of print</small></div>

<div><h4>Noncardiac comorbidities and intensive up-titration of oral treatment in patients recently hospitalized for heart failure: insights from the STRONG-HF trial.</h4><i>Chioncel O, Davison B, Adamo M, Antohi LE, ... Cotter G, Mebazaa A</i><br /><b>Aims</b><br />To assess the potential interaction between noncardiac comorbidities (NCCs) and the efficacy and safety of high intensity care (HIC) versus usual care (UC) in STRONG-HF trial, including stable patients with improved but still elevated NPs METHODS AND <br /><b>Results:</b><br/>In the trial, 8 NCCs were reported: anemia, diabetes, renal dysfunction, severe liver disease, COPD/asthma, stroke/TIA, psychiatric/neurological disorders, and malignancies. Patients were classified by NCC number (0, 1, 2 and ≥3). The treatment effect of HIC versus UC on the primary endpoint, 180-day death or HF-rehospitalization, was compared by NCC number and by each individual comorbidity. Among the 1078 patients, the prevalence of 0, 1, 2 and ≥3 NCCs was 24.3%, 39.8%, 24.5% and 11.3%. Achievement of full doses of HF-therapies at 90- and 180-days in the HIC was similar irrespective of NCCs number. In the HIC, the primary endpoint occurred in 10.0%, 16,6%, 13,6% and 26,2%, in those with 0, 1, 2 and ≥3 NCCs, as compared to 19,1%, 25,4%, 23,3% and 26,2% in UC (interaction-p=0.80). The treatment benefit of HIC vs. UC on the primary endpoint didn\'t differ significantly by each individual comorbidity. There was no significant treatment interaction by NCC number in quality-of-life improvement (p=0.98) or the incidence of serious adverse events (p=0.11).<br /><b>Conclusions</b><br />In the STRONG-HF trial, non-cardiac comorbidities neither limited the rapid up-titration of HF-therapies, nor attenuated the benefit of HIC on primary endpoint. In the context of a clinical trial, the benefit-risk ratio favors the rapid up-titration of HF-therapies even in patients with multiple NCCs This article is protected by copyright. All rights reserved.<br /><br />This article is protected by copyright. All rights reserved.<br /><br /><small>Eur J Heart Fail: 20 Sep 2023; epub ahead of print</small></div>

<div><h4>Practical Algorithms for Early Diagnosis of Heart Failure and Heart Stress using NT-proBNP: A Clinical Consensus Statement from the Heart Failure Association of the ESC.</h4><i>Bayes-Genis A, Doherty KF, Petrie MC, Januzzi JL, ... Metra M, Rosano G</i><br /><AbstractText>Diagnosing heart failure is often difficult due to the nonspecific nature of the symptoms, which can be caused by a range of medical conditions. Natriuretic peptides (NPs) have been recognized as important biomarkers for diagnosing heart failure. This document from the Heart Failure Association examines the practical uses of NT-proBNP in various clinical scenarios. The concentrations of NT-proBNP vary according to the patient profile and the clinical scenario, therefore values should be interpreted with caution to ensure appropriate diagnosis. Validated cut-points are provided to rule-in or rule-out acute heart failure in the emergency department and to diagnose de novo heart failure in the out-patient setting. We also coin the concept of \"heart stress\" when NT-proBNP levels are elevated in a asymptomatic patients with risk factors for heart failure (i.e diabetes, hypertension, CAD); underlying the development of cardiac dysfunction and further increased risk. We propose a simple acronym for healthcare professionals and patients, FIND-HF, which serves as a prompt to consider heart failure: Fatigue, Increased water accumulation, Natriuretic peptide testing, and Dyspnoea. Use of this acronym would enable the early diagnosis of heart failure. Overall, understanding and utilizing NT-proBNP levels will lead to earlier and more accurate diagnoses of HF ultimately improving patient outcomes and reducing healthcare costs. This article is protected by copyright. All rights reserved.</AbstractText><br /><br />This article is protected by copyright. All rights reserved.<br /><br /><small>Eur J Heart Fail: 15 Sep 2023; epub ahead of print</small></div>

<div><h4>Assessing the association between genetic and phenotypic features of dilated cardiomyopathy and outcome in patients with coronary artery disease.</h4><i>Jones RE, Hammersley DJ, Zheng S, McGurk KA, ... Ware JS, Prasad SK</i><br /><b>Aims</b><br />To examine the relevance of genetic and cardiovascular magnetic resonance (CMR) features of dilated cardiomyopathy (DCM) in individuals with coronary artery disease (CAD).<br /><b>Methods and results</b><br />This study includes 2 cohorts. First, individuals with CAD recruited into the UK Biobank (UKB) were evaluated. Second, patients with CAD referred to a tertiary centre for evaluation with late gadolinium enhancement (LGE)-CMR were recruited (London cohort); patients underwent genetic sequencing as part of the research protocol and long-term follow-up. From 31,154 individuals with CAD recruited to UKB, rare pathogenic variants in DCM genes were associated with increased risk of death or major adverse cardiac events (HR 1.57, 95% confidence interval [CI] 1.22-2.01, p<0.001). Of 1,619 individuals with CAD included from the UKB CMR substudy, participants with a rare variant in a DCM-associated gene had lower left ventricular ejection fraction (LVEF) compared to genotype negative individuals (mean 47±10% vs 57±8%, p<0.001). Of 453 patients in the London cohort, 63 (14%) had non-infarct pattern LGE (NI-LGE) on CMR. Patients with NI-LGE had lower LVEF (mean 38±18% vs 48±16%, p<0.001) compared to patients without NI-LGE, with no significant difference in the burden of rare protein altering variants in DCM-associated genes between groups (9.7% vs 6.7%, odds ratio 1.5, 95% CI 0.5-4.4, p=0.41). NI-LGE was not independently associated with adverse clinical outcomes.<br /><b>Conclusion</b><br />Rare pathogenic variants in DCM-associated genes impact LV remodelling and outcomes in stable CAD. NI-LGE is associated with adverse remodelling but is not an independent predictor of outcome and had no rare genetic basis in our study. This article is protected by copyright. All rights reserved.<br /><br />This article is protected by copyright. All rights reserved.<br /><br /><small>Eur J Heart Fail: 13 Sep 2023; epub ahead of print</small></div>

<div><h4>Heart failure patients with improved ejection fraction: insights from the MECKI Score database.</h4><i>Agostoni P, Pluchinotta FR, Salvioni E, Mapelli M, ... Piepoli M, MECKI score research group</i><br /><b>Aims</b><br />Improvement of left ventricular ejection fraction is a major goal of heart failure (HF) treatment. However, data on clinical characteristics, exercise performance and prognosis in HF patients who improved ejection fraction (HFimpEF) are scarce. The study aimed to determine whether HFimpEF patients have a distinct clinical phenotype, biology and prognosis than HF patients with persistently reduced ejection fraction (pHFrEF).<br /><b>Methods and results</b><br />7948 patients enrolled in the Metabolic Exercise Cardiac Kidney Indexes (MECKI) score database were evaluated (median follow-up of 1490 days). We analyzed clinical, laboratory, ECG, echocardiographic, exercise, and survival data from HFimpEF (n = 1504) and pHFrEF (n = 6017) patients. The primary endpoint of the study was the composite of cardiovascular death, left ventricular assist device implantation, and urgent heart transplantation. HFimpEF patients had lower HF severity: LVEF 44.0[41.0-47.0] vs. 29.7[24.1-34.5]%, BNP 122[65-296] vs. 373[152-888] pg/mL, hemoglobin 13.5[12.2-14.6] vs. 13.7[12.5-14.7] g/dL, renal function by MDRD 72.0[56.7-89.3] vs. 70.4[54.5-85.3] mL/min, peakVO<sub>2</sub> 62.2[50.7-74.1] vs. 52.6[41.8-64.3]%pred, VE/VCO<sub>2</sub> slope 30.0[26.9-34.4] vs. 32.1[28.0-38.0] in HFimpEF and pHFrEF, respectively (p < 0.001 for all). Cardiovascular mortality rates were 26.6 and 46.9 per 1000 person-years for HFimpEF and pHFrEF, respectively (p < 0.001). Kaplan-Meier analysis showed that HFimpEF had better a long-term prognosis compared with pHFrEF patients. After adjustment for variables differentiating HFimpEF from pHFrEF, except echocardiographic parameters, the Kaplan-Meier curves showed the same prognosis.<br /><b>Conclusions</b><br />HFimpEF represents a peculiar group of HF patients whose clinical, laboratory, ECG, echocardiographic, and exercise characteristics parallel the recovery of systolic function. Nonetheless, these patients remain at risk for adverse outcome. This article is protected by copyright. All rights reserved.<br /><br />This article is protected by copyright. All rights reserved.<br /><br /><small>Eur J Heart Fail: 13 Sep 2023; epub ahead of print</small></div>

<div><h4>Supervised exercise training in patients with advanced heart failure and left ventricular assist device: a multicenter randomized controlled trial (Ex-VAD trial).</h4><i>Feuerstein A, Schoenrath F, Belyavskiy E, Knierim J, ... Pieske B, Edelmann F</i><br /><b>Aims</b><br />Small studies and observations suggested that exercise training may improve peak oxygen consumption (peakVO<sub>2</sub> ) in patients with advanced heart failure and left ventricular assist device (LVAD). We investigated whether in this patient group a supervised exercise training can improve exercise capacity.<br /><b>Methods and results</b><br />In this multicenter, prospective, randomized, controlled trial patients with stable heart failure and LVAD were randomly assigned (2:1) to 12 weeks of supervised exercise training or usual care, with 12 weeks of follow-up. The primary endpoint was the change in peakVO<sub>2</sub> after 12 weeks (51 patients provided a power of 90% with an expected group difference in peakVO<sub>2</sub> of 3 ml/kg/min). Secondary endpoints included changes in submaximal exercise capacity and quality of life. Among 64 patients enrolled (97% male, mean age 56 years) 54 were included in the analysis. Mean difference in the change of peakVO<sub>2</sub> after 12 weeks was 0.826 ml/min/kg (95% CI -0.37, 2.03; p=0.183). There was a positive effect of exercise training on 6-minute walk distance with a mean increase in the intervention group by 43.4 meters (95% CI 16.9, 69.9; p=0.0024), and on the Kansas City Cardiomyopathy Questionnaire physical domain score (mean 14.3, 95% CI 3.7, 24.9; p=0.0124), both after 12 weeks. The overall adherence was high (71%), and there were no differences in adverse events between groups.<br /><b>Conclusion</b><br />In patients with advanced heart failure and LVAD 12 weeks of exercise training did not improve peakVO<sub>2</sub> but demonstrated positive effects on submaximal exercise capacity and physical quality of life. This article is protected by copyright. All rights reserved.<br /><br />This article is protected by copyright. All rights reserved.<br /><br /><small>Eur J Heart Fail: 13 Sep 2023; epub ahead of print</small></div>

<div><h4>Personalized lifetime prediction of survival and treatment benefit in patients with heart failure with reduced ejection fraction: the LIFE-HF model.</h4><i>Burger PM, Savarese G, Tromp J, Adamson C, ... Mosterd A, European Society of Cardiology\'s Cardiovascular Risk Collaboration (ESC CRC)</i><br /><b>Aims</b><br />Although trials have proven the group-level effectiveness of various therapies for heart failure with reduced ejection fraction (HFrEF), important differences in absolute effectiveness exist between individuals. We developed and validated the LIFEtime-perspective for Heart Failure (LIFE-HF) model for the prediction of individual (lifetime) risk and treatment benefit in patients with HFrEF.<br /><b>Methods and results</b><br />Cox proportional hazards functions with age as the time scale were developed in the PARADIGM-HF and ATMOSPHERE trials (n = 15,415). Outcomes were cardiovascular death, HF hospitalization or cardiovascular death, and non-cardiovascular mortality. Predictors were age, sex, New York Heart Association class, prior HF hospitalization, diabetes mellitus, extracardiac vascular disease, systolic blood pressure, left ventricular ejection fraction, N-terminal pro-B-type natriuretic peptide, and glomerular filtration rate. The functions were combined in life-tables to predict individual overall and HF hospitalization-free survival. External validation was performed in the SwedeHF registry, ASIAN-HF registry, and DAPA-HF trial (n = 51,286). Calibration of 2- to 10-year risk was adequate, and c-statistics were 0.65-0.74. An interactive tool was developed combining the model with hazard ratios from trials to allow estimation of an individual\'s (lifetime) risk and treatment benefit in clinical practice. Applying the tool to the development cohort, combined treatment with a mineralocorticoid receptor antagonist (MRA), sodium/glucose cotransporter 2 (SGLT2) inhibitor, and angiotensin receptor-neprilysin inhibitor (ARNI) was estimated to afford a median of 2.5 (interquartile range [IQR] 1.7-3.7) and 3.7 (IQR 2.4-5.5) additional years of overall and HF hospitalization-free survival respectively.<br /><b>Conclusion</b><br />The LIFE-HF model enables estimation of lifelong overall and HF hospitalization-free survival, and (lifetime) treatment benefit for individual patients with HFrEF. It could serve as a tool to improve the management of HFrEF by facilitating personalized medicine and shared decision-making.<br /><br />This article is protected by copyright. All rights reserved.<br /><br /><small>Eur J Heart Fail: 10 Sep 2023; epub ahead of print</small></div>

<div><h4>Impella and venoarterial extracorporeal membrane oxygenation in cardiogenic shock complicating acute myocardial infarction.</h4><i>Bogerd M, Ten Berg S, Peters EJ, Vlaar APJ, ... Schrage B, Henriques JPS</i><br /><b>Aims</b><br />This research aimed to give contemporary insight into the use of Impella and venoarterial extracorporeal membrane oxygenation (VA-ECMO) in myocardial infarction-related cardiogenic shock (AMICS) and into associated outcomes, adverse events, and resource demands.<br /><b>Methods and results</b><br />This nationwide observational cohort study describes all AMICS patients treated with Impella(ABIOMED, Danvers, USA) and/or VA-ECMO in 2020-2021. Impella and/or VA-ECMO were used in 20% of all AMICS cases(n = 4088). Impella patients were older (34% vs 13% >75 years, p < 0.001) and less frequently presented after an out-of-hospital cardiac arrest (18% vs. 40%, p < 0.001). In-hospital mortality was lower in the Impella versus VA-ECMO cohort (61% vs. 67%, p = 0.001). Adverse events occurred less frequently in Impella-supported patients: Acute haemorrhagic anaemia (36% vs. 68%, p < 0.001), cerebrovascular accidents (4% vs. 11%, p < 0.001), thromboembolisms of the extremities (5% vs. 8%, p < 0.001), systemic inflammatory response syndrome (21% vs. 25%, p = 0.004), acute kidney injury (44% vs. 53%, p < 0.001), and acute liver failure (7% vs. 12%, p < 0.001). Impella patients were discharged home directly more often (20% vs. 11%, p < 0.001) whereas VA-ECMO patients were more often discharged to another care facility (22% vs. 19%, p = 0.031). Impella patients had shorter hospital stays and lower hospital costs.<br /><b>Conclusion</b><br />This is the largest, most recent European cohort study describing outcomes, adverse events, and resource demands based on claims data in patients with Impella and/or VA-ECMO. Overall, adverse event rates and resource consumption were high. Given the current lack of beneficial evidence, our study reinforces the need for prospectively established, high-quality evidence to guide clinical decision making. This article is protected by copyright. All rights reserved.<br /><br />This article is protected by copyright. All rights reserved.<br /><br /><small>Eur J Heart Fail: 06 Sep 2023; epub ahead of print</small></div>

<div><h4>Comorbidities and Clinical Response to Cardiac Resynchronization Therapy: Patient-Level Meta-analysis From Eight Clinical Trials.</h4><i>Fudim M, Dalgaard F, Friedman DJ, Abraham WT, ... Al-Khatib SM, Sanders GD</i><br /><b>Background</b><br />Patients with heart failure usually have several other medical conditions that might alter the effects of interventions. We investigated whether the burden of comorbidity modified the clinical response to cardiac resynchronization therapy (CRT).<br /><b>Methods and results</b><br />Original patient-level data from eight randomized trials exploring the effects of CRT versus no CRT were pooled (BLOCK HF, MIRACLE, MIRACLE-ICD, MIRACLE-ICD-II, RAFT, COMPANION, MADIT-CRT and REVERSE). A prior history of the following comorbidities was considered: episodic or persistent atrial fibrillation (AF; n = 920), coronary artery disease (CAD; n = 3732), diabetes (n = 2171), and hypertension (n = 3353). Patients were classified into three groups based on the number of comorbidities: 0, 1-2, or ≥3. The outcomes of interest were time to all-cause mortality and time to the composite outcome of heart failure hospitalization (HFH) or all-cause mortality. Outcomes were evaluated within each co-morbidity group using a Bayesian Hierarchical Weibull survival regression model. Of 6324 patients, 970 (15%) had no comorbidities, 4052 (64%) had 1-2 and 1302 (21%) had ≥3 comorbidities. The adjusted hazard ratio (aHR) for CRT versus no CRT for all-cause mortality in the overall cohort was 0.79 (95% credible interval [CI] 0.68-0.93) (p = 0.01); for no comorbidities the aHR was 0.54 (95% CI 0.34-0.86), for 1-2 comorbidities was 0.81 (95% CI 0.67-0.97) and for ≥3 comorbidities was 0.83 (95% CI 0.64-1.07) (no significant interaction between CRT and comorbidity burden: p = 0.13). For the endpoint of HFH or all-cause mortality, the aHR for the overall cohort was 0.74, (95% CI 0.65-0.84) (p = 0.001), for no comorbidities was 0.69, (95% CI 0.50-0.94), for 1-2 comorbidities was 0.77, (95% CI 0.66-0.90) and for ≥3 comorbidities was 0.68, (95% CI 0.55-0.82) (no significant interaction between CRT and comorbidity burden: p = 0.081).<br /><b>Conclusion</b><br />In a meta-analysis of patient-level data from eight major trials, the totality of evidence suggests that CRT reduces HFH and/or all-cause mortality even when several comorbid diseases are present. This article is protected by copyright. All rights reserved.<br /><br />This article is protected by copyright. All rights reserved.<br /><br /><small>Eur J Heart Fail: 06 Sep 2023; epub ahead of print</small></div>

<div><h4>Associations between baseline heart rate and blood pressure and time to events in HFrEF patients: data from the QUALIFY international registry.</h4><i>Abdin A, Anker SD, Cowie MR, Filippatos GS, ... Komajda M, Böhm M</i><br /><b>Aims</b><br />A high resting heart rate (RHR) and low systolic blood pressure (SBP) are a risk factor and a risk indicator, respectively, for poor heart failure (HF) outcomes. This analysis evaluates the associations between baseline RHR and SBP with outcomes and treatment patterns in HF patients with reduced ejection fraction (HFrEF) in the QUALIFY international registry.<br /><b>Methods and results</b><br />Between September 2013 and December 2014, 7317 HFrEF patients with a previous HF hospitalization within 1-15 months were enrolled in the QUALIFY registry (Quality of Adherence to Guideline Recommendations for Life-Saving Treatment in Heart Failure Survey). Complete follow-up data were available for 5138 patients. The relationships between RHR and SBP and outcomes were assessed using a Cox proportional hazards model and were analyzed according to baseline values as high RHR (H-RHR) ≥ 75 vs. low RHR (L-RHR) < 75 bpm) and high SBP (H-SBP): ≥ 110 vs. low SBP (L-SBP): <110 mmHg and analyzed according to each of the following 4 phenotypes: (H-RHR/L-SBP, L-RHR/L-SBP, H-RHR/H-SBP and L-RHR/H-SBP (reference group). Compared to the reference group, H-RHR/L-SBP was associated with the worst outcomes for the combined primary endpoint of CV death and HF hospitalization (HR 1.83, CI 1.51-2.21, p<0.001), CV death (HR 2.7, CI 1.69-4.33, p <0.001), and HF hospitalization (HR 1.62, CI 1.30-2.01, p<0.001). Low-risk patients with L-RHR/H-SBP achieved more frequently >=50% of target doses of ACEIs and BBs than the other groups. However, 48% and 46% of low-risk patients were not well treated with ACEIs and BBs, respectively (<=50% of target dose or no treatment).<br /><b>Conclusion</b><br />In patients with HFrEF and recent hospitalisation, elevated RHR and lower SBP identify patients at increased risk for CV endpoints. While SBP and RHR are often recognized as barriers that deter physicians from treating with high doses of recommended drugs, they are not the only reason leaving many patients suboptimally treated. This article is protected by copyright. All rights reserved.<br /><br />This article is protected by copyright. All rights reserved.<br /><br /><small>Eur J Heart Fail: 04 Sep 2023; epub ahead of print</small></div>

<div><h4>Haemodynamic and metabolic phenotyping of patients with aortic stenosis and preserved ejection fraction: a specific phenotype of HFpEF?</h4><i>De Biase N, Mazzola M, Del Punta L, Di Fiore V, ... Masi S, Pugliese NR</i><br /><b>Background</b><br />Degenerative aortic valve stenosis with preserved left ventricular ejection fraction (ASpEF) and heart failure with preserved left ventricular ejection fraction (HFpEF) display intriguing similarities. We designed this study to provide a non-invasive, comparative analysis of ASpEF versus HFpEF at rest and during exercise.<br /><b>Methods and results</b><br />We prospectively enrolled 148 patients with HFpEF and 150 patients with degenerative moderate-to-severe ASpEF, together with 66 age- and sex-matched healthy controls. All subjects received a comprehensive evaluation at rest and 351/364 (96%) performed a combined cardiopulmonary-exercise stress echocardiography test. Patients with ASpEF eligible for transcatheter aortic valve replacement (n=125) also performed cardiac computed tomography (CT). HFpEF and ASpEF patients showed similar demographic distribution and biohumoral profiles. Most patients with ASpEF (134/150, 89%) had severe high-gradient aortic stenosis; 6/150 (4%) had normal-flow, low-gradient ASpEF, while 10/150 (7%) had low-flow, low-gradient ASpEF. Both patient groups displayed significantly lower peak oxygen consumption (VO<sub>2</sub> ), peak cardiac output, and peak arteriovenous oxygen difference compared to controls (all p<0.01). ASpEF patients showed several extravalvular abnormalities at rest and during exercise, similar to HFpEF (all p<0.01 vs controls). Epicardial adipose tissue (EAT) thickness was significantly greater in ASpEF than HFpEF and was inversely correlated with peak VO<sub>2</sub> in all groups. In ASpEF, EAT was directly related to echocardiography-derived disease severity and CT-derived aortic valve calcium burden.<br /><b>Conclusions</b><br />Functional capacity is similarly impaired in ASpEF and HFpEF due to both peripheral and central components. Further investigation is warranted to determine whether extravalvular alterations may affect disease progression and prognosis in ASpEF even after valve intervention, which could support the concept of ASpEF as a specific subphenotype of HFpEF. This article is protected by copyright. All rights reserved.<br /><br />This article is protected by copyright. All rights reserved.<br /><br /><small>Eur J Heart Fail: 01 Sep 2023; epub ahead of print</small></div>

<div><h4>Relationship Between Baseline Electrocardiographic Measurements and Outcomes in Patients with High-Risk Heart Failure: Insights from the VerICiguaT Global Study in Subjects With Heart Failure With Reduced Ejection Fraction (VICTORIA) Trial.</h4><i>Yogasundaram H, Zheng Y, Ly E, Ezekowitz J, ... Sandhu RK, VICTORIA Study Group.</i><br /><b>Aims</b><br />Whether electrocardiographic (ECG) measurements predict mortality in chronic heart failure with reduced ejection fraction (HFrEF) is unknown.<br /><b>Methods</b><br />We studied 4880 patients from the Vericiguat Global Study in Subjects with Heart Failure with Reduced Ejection Fraction (VICTORIA) trial with a baseline 12-lead ECG. Associations between ECG measurements and mortality were estimated as hazard ratios (HR) and adjusted for the Meta-Analysis Global Group in Chronic Heart Failure (MAGGIC) risk score, N-terminal pro-B-type natriuretic peptide, and index event. Select interactions between ECG measurements, patient characteristics and mortality were examined.<br /><b>Results</b><br />Over a median of 10.8 months, there were 824 cardiovascular (CV) deaths (214 sudden) and 1005 all-cause deaths. Median age was 68 years [interquartile range (IQR) 60-76], 24% were women, median ejection fraction was 30% (IQR 25-55), 41% had New York Heart Association class III/IV, and median MAGGIC score was 24 (IQR 19-28). After multivariable adjustment, significant associations existed between heart rate (per 5 beats/min: HR 1.02), QRS duration (per 10 ms: HR 1.02), absence of left ventricular hypertrophy (HR 0.64) and CV death, and similarly so with all-cause death (HR 1.02; HR 1.02; HR 0.61, respectively). Contiguous pathologic Q waves were significantly associated with sudden death (HR 1.46), and right ventricular hypertrophy with all-cause death (HR 1.44). The only sex-based interaction observed was for pathologic Q waves on CV (men: HR 1.05; women: HR 1.64, p<sub>interaction</sub> =0.024) and all-cause death (men: HR 0.99; women: HR 1.57; p<sub>interaction</sub> =0.010). Whereas sudden death doubled in females, it did not differ among males (male: HR 1.25, 95% CI 0.87-1.79; female: HR 2.50, 95% CI 1.23-5.06; p<sub>interaction</sub> =0.141).<br /><b>Conclusion</b><br />Routine ECG measurements provide additional prognostication of mortality in high-risk HFrEF patients, particularly in women with contiguous pathologic Q waves. This article is protected by copyright. All rights reserved.<br /><br />This article is protected by copyright. All rights reserved.<br /><br /><small>Eur J Heart Fail: 01 Sep 2023; epub ahead of print</small></div>

<div><h4>Early Left Atrial Venting versus Conventional Treatment for Left Ventricular Decompression during Venoarterial Extracorporeal Membrane Oxygenation Support: The EVOLVE-ECMO Randomised Clinical Trial.</h4><i>Park H, Yang JH, Ahn JM, Kang DY, ... Park SJ, Kim MS</i><br /><b>Aims</b><br />Few studies have reported data on the optimal timing of left ventricular (LV) unloading during venoarterial extracorporeal membrane oxygenation (VA-ECMO) for cardiac arrest or shock. This study evaluated the feasibility of an early LV unloading strategy compared with a conventional strategy in VA-ECMO.<br /><b>Methods and results</b><br />Between December 2018 and August 2022, 60 patients at two institutions were randomised in a 1:1 ratio to receive early (n = 30) or conventional (n = 30) LV unloading strategies. The early LV unloading strategy was defined as LV unloading performed at the time of VA-ECMO insertion. LV unloading was performed using a percutaneous transseptal left atrial cannulation via the femoral vein incorporated into the ECMO venous circuit. The early and conventional LV unloading groups included 29 (96.7%) and 23 (76.7%) patients, respectively (median time from VA-ECMO insertion to LV unloading: 48.4 h, interquartile range 47.8-96.5 h). The groups showed no significant differences in the rate of VA-ECMO weaning as the primary endpoint (70.0% vs. 76.7%; relative risk, 0.91; 95% confidence interval, 0.67-1.24; P = 0.386) and survival to discharge (53.3% vs. 50.0%, P = 0.796). However, the pulmonary congestion score index at 48 h after LV unloading was significantly improved only in the early LV unloading group (2.0 ± 0.7 vs. 1.7 ± 0.6 at baseline vs. at 48 h; P = 0.008).<br /><b>Conclusion</b><br />Compared with the conventional approach, early LV unloading did not improve the VA-ECMO weaning rate, despite the rapid improvement in pulmonary congestion. Therefore, the results of this study do not support the application of this strategy after VA-ECMO insertion.<br /><br />This article is protected by copyright. All rights reserved.<br /><br /><small>Eur J Heart Fail: 29 Aug 2023; epub ahead of print</small></div>

<div><h4>Association between epicardial adipose tissue and cardiac dysfunction in subjects with severe obesity.</h4><i>Chin JF, Aga YS, Kamar SA, Kroon D, ... de Boer RA, van Dalen BM</i><br /><b>Background</b><br />Epicardial adipose tissue (EAT) plays a role in obesity-related heart failure with preserved ejection fraction. However, the association of EAT thickness with the development of cardiac dysfunction in subjects with severe obesity without known cardiovascular disease is unclear.<br /><b>Aims</b><br />Determine the association between EAT thickness and cardiac dysfunction and describe the potential value of EAT as an early marker of cardiac dysfunction.<br /><b>Methods and results</b><br />Subjects with BMI ≥35 kg/m<sup>2</sup> aged 35 to 65 years, who were referred for bariatric surgery, without suspicion of or known cardiac disease, were enrolled. Conventional transthoracic echocardiography and strain analyses were performed. A total of 186 subjects were divided into tertiles based on EAT thickness, of whom 62 were in EAT-1 (EAT <3.8 mm), 63 in EAT-2 (EAT 3.8-5.4 mm), and 61 in EAT-3 (EAT >5.4 mm). Parameters of systolic and diastolic function were comparable between tertiles. Patients in EAT-3 had the lowest global longitudinal strain (GLS) and left atrial contractile strain (LASct). Linear regression showed that a one-unit increase in EAT thickness (mm) was independently associated with a decrease in GLS (%) (β-coefficient - 0.404, p = 0.002), and a decrease in LASct (%) (β-coefficient - 0.544, p = 0.027). Furthermore, EAT-3 independently predicted cardiac dysfunction as defined by a GLS < 18% (OR 2.8, p = 0.013) and LASct<14% (OR 2.5, p = 0.045).<br /><b>Conclusions</b><br />Increased EAT thickness in subjects with obesity without known cardiac disease was independently associated with subclinical cardiac dysfunction. Our findings suggest that EAT might play a role in the early stages of cardiac dysfunction in obesity before this may progress to overt clinical disease. This article is protected by copyright. All rights reserved.<br /><br />This article is protected by copyright. All rights reserved.<br /><br /><small>Eur J Heart Fail: 29 Aug 2023; epub ahead of print</small></div>