Search

Abstract Aims The objective of this study was to examine associations between elevated depressive symptoms and increased risk of adverse clinical events patients with heart failure and reduced ejection fraction (HFrEF), as well as the potential contribution of health behaviours. Methods and results One hundred forty‐two men and women with HFrEF were enrolled through heart failure (HF) clinics and followed over time. At baseline and 6 months, depressive symptoms were assessed by the Beck Depression Inventory‐II (BDI‐II) and HFrEF disease activity by B‐type natriuretic peptide (BNP). The Self‐Care of Heart Failure Index (SCHFI) was used to assess HF self‐care behaviours. Proportional hazards regression models assessed the contribution of depressive symptoms and HFrEF disease biomarkers on death or cardiovascular hospitalization. Over a median follow‐up period of 4 years, 42 patients (30%) died, and 84 (60%) had cardiovascular hospitalizations. A 10‐point higher baseline BDI‐II score was associated with a 35% greater risk of death or cardiovascular hospitalization. Higher baseline BDI‐II scores were associated with poorer HF self‐care maintenance behaviours (R = −0.30, P

Abstract Aims This study aimed to examine the diagnostic pathways and outcomes of patients with heart failure (HF), stratified by left ventricular ejection fraction (EF), and to highlight deficiencies in real‐world HF diagnosis and management. Methods and results We conducted a retrospective cohort study in Salford, United Kingdom, utilizing linked primary and secondary care data for HF patients diagnosed between January 2010 and November 2019. We evaluated characteristics, diagnostic patterns, healthcare resource utilization, and outcomes. Patients were categorized according to baseline (the latest measure prior to or within 90 days post‐diagnosis) as having HF with reduced EF (HFrEF), mildly reduced EF (HFmrEF), or preserved EF (HFpEF). The data encompassed a 2 year period before diagnosis and up to 5 years post‐diagnosis. A total of 3227 patients were diagnosed with HF between January 2010 and November 2019. The mean follow‐up time was 2.6 [±1.9 standard deviation (SD)] years. The mean age at diagnosis was 74.8 (±12.7 SD) years, and 1469 (45.5%) were female. HFpEF was the largest cohort (46.6%, npEF = 1505), HFmrEF constituted 16.1% (nmrEF = 520), and HFrEF 18.5% (nrEF = 596) of the population, while 18.8% (nu = 606) of patients remained unassigned due to insufficient evidence to support categorization. At baseline, measurement of natriuretic peptide (NP; brain NP and N‐terminal pro‐B‐type NP) and echocardiographic report data were available for 592 (18.3%) and 2621 (81.2%) patients, respectively. A total of 2099 (65.0%) of the HF cohort had access to a cardiology‐led outpatient clinic prior to the HF diagnosis, and 602 (18.7%) attended cardiac rehabilitation post‐diagnosis. The 5 year crude survival rate was 37.8% [95% confidence interval (CI) (35.2–40.7%)], 42.3% [95% CI (38.0–47.2%)], and 45.5% [95% CI (41.0–50.4%)] for HFpEF, HFrEF, and HFmrEF, respectively. Conclusions Low survival rates were observed across all HF groups, along with suboptimal rates of NP testing and specialist assessments. These findings suggest missed opportunities for timely and accurate HF diagnosis, a pivotal first step in improving outcomes for HF patients. Addressing these gaps in diagnosis and management is urgently needed.

Abstract The purpose of this study was to systematically review the development, performance, and applicability of prognostic models developed for predicting poor events in patients with heart failure with preserved ejection fraction (HFpEF). Databases including Embase, PubMed, Web of Science Core Collection, the Cochrane Library, China National Knowledge Infrastructure, Wan Fang, Wei Pu, and China Biological Medicine were queried from their respective dates of inception to 1 June 2023, to examine multivariate models for prognostic prediction in HFpEF. Both forward and backward citations of all studies were included in our analysis. Two researchers individually used the Critical Appraisal and Data Extraction for Systematic Reviews of Prediction Modelling Studies (CHARMS) checklist to extract data and assess the quality of the models using the Predictive Mode Bias Risk Assessment Tool (PROBAST). Among the 6897 studies screened, 16 studies derived and/or validated a total of 39 prognostic models. The sample size ranges for model development, internal validation, and external validation are 119 to 5988, 152 to 1000, and 30 to 5957, respectively. The most frequently employed modelling technique was Cox proportional hazards regression. Six studies (37.50%) conducted internal validation of models; bootstrap and k‐fold cross‐validation were the commonly used methods for internal validation of models. Ten of these models (25.64%) were validated externally, with reported the c‐statistic in the external validation set ranging from 0.70 to 0.96, while the remaining models await external validation. The MEDIA echo score and I‐PRESERVE‐sudden cardiac death prediction mode have been externally validated using multiple cohorts, and the results consistently show good predictive performance. The most frequently used predictors identified among the models were age, n‐terminal pro‐brain natriuretic peptide, ejection fraction, albumin, and hospital stay in the last 5 months owing to heart failure. All study predictor domains and outcome domains were at low risk of bias, high or unclear risk of bias of all prognostic models due to underreporting in the area of analysis. All studies did not evaluate the clinical utility of the prognostic models. Predictive models for predicting prognostic outcomes in patients with HFpEF showed good discriminatory ability but their utility and generalization remain uncertain due to the risk of bias, differences in predictors between models, and the lack of clinical application studies. Future studies should improve the methodological quality of model development and conduct external validation of models.

Background Optimal medical treatment can lead to improvement in left ventricular ejection fraction (LVEF) in patients with heart failure with reduced EF (HFrEF). We investigated the characteristics, predictors, and outcomes of HFrEF according to the 1‐year LVEF following angiotensin receptor–neprilysin inhibitors therapy (ARNI). Methods and Results Using the STRATS‐HF‐ARNI (Strain for Risk Assessment and Therapeutic Strategies in Patients With Heart Failure Treated With Angiotensin Receptor‐Neprilysin Inhibitor) registry, we identified 1074 patients with HFrEF who took ARNI and underwent baseline and 1‐year echocardiography. Patients were classified as HF with improved ejection fraction (HFimpEF) and persistent HFrEF (perHFrEF) (1‐year LVEF >40% and ≤40%). The primary and secondary outcomes were all‐cause and cardiac mortality from the 1‐year follow‐up. Among 1074 included patients, 498 (46.4%) had HFimpEF, and 576 (53.6%) had perHFrEF. Older age, male sex, and large LV end‐diastolic volumes were positive predictors of perHFrEF, whereas atrial fibrillation and high systolic blood pressure were identified as inverse predictors. Patients with HFimpEF showed lower all‐cause and cardiac mortality rates (both log‐rank P

Background Prognostic markers and biological pathways linked to detrimental clinical outcomes in heart failure with preserved ejection fraction (HFpEF) remain incompletely defined. Methods and Results We measured serum levels of 4123 unique proteins in 1117 patients with HFpEF enrolled in the PARAGON‐HF (Efficacy and Safety of LCZ696 Compared to Valsartan, on Morbidity and Mortality in Heart Failure Patients With Preserved Ejection Fraction) trial using a modified aptamer proteomic assay. Baseline circulating protein concentrations significantly associated with the primary end point and the timing and occurrence of total heart failure hospitalization and cardiovascular death were identified by recurrent events regression, accounting for multiple testing, adjusted for age, sex, treatment, and anticoagulant use, and compared with published analyses in 2515 patients with heart failure with reduced ejection fraction from the PARADIGM‐HF (Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure) and ATMOSPHERE (Efficacy and Safety of Aliskiren and Aliskiren/Enalapril Combination on Morbidity–Mortality in Patients With Chronic Heart Failure) clinical trials. We identified 288 proteins that were robustly associated with the risk of heart failure hospitalization and cardiovascular death in patients with HFpEF. The baseline proteins most strongly related to outcomes included B2M (β‐2 microglobulin), TIMP1 (tissue inhibitor of matrix metalloproteinase 1), SERPINA4 (serpin family A member 4), and SVEP1 (sushi, von Willebrand factor type A, EGF, and pentraxin domain containing 1). Overall, the protein–outcome associations in patients with HFpEF did not markedly differ as compared with patients with heart failure with reduced ejection fraction. A proteomic risk score derived in patients with HFpEF was not superior to a previous proteomic score derived in heart failure with reduced ejection fraction nor to clinical risk factors, NT‐proBNP (N‐terminal pro‐B‐type natriuretic peptide), or high‐sensitivity cardiac troponin. Conclusions Numerous serum proteins linked to metabolic, coagulation, and extracellular matrix regulatory pathways were associated with worse HFpEF prognosis in the PARAGON‐HF proteomic substudy. Our results demonstrate substantial similarities among serum proteomic risk markers for heart failure hospitalization and cardiovascular death when comparing clinical trial participants with heart failure across the ejection fraction spectrum. Registration URL: https://www.clinicaltrials.gov; Unique Identifiers: NCT01920711, NCT01035255, NCT00853658.

Abstract Aims Patients with heart failure (HF) with reduced ejection fraction (EF) (HFrEF), mildly reduced EF (HFmrEF), and preserved EF (HFpEF) may all progress to advanced HF, but the impact of EF in the advanced setting is not well established. Our aim was to assess the prognostic impact of EF in patients with at least one ‘I NEED HELP’ marker for advanced HF. Methods and results Patients with HF and at least one high‐risk ‘I NEED HELP’ criterion from four centres were included in this analysis. Outcomes were assessed in patients with HFrEF (EF ≤ 40%), HFmrEF (EF 41–49%), and HFpEF (EF ≥ 50%) and with EF analysed as a continuous variable. The prognostic impact of medical therapy for HF in patients with EF 50% was also evaluated. All‐cause death was the primary endpoint, and cardiovascular death was a secondary endpoint. Among 1149 patients enrolled [mean age 75.1 ± 11.5 years, 67.3% males, 67.6% hospitalized, median follow‐up 260 days (inter‐quartile range 105–390 days)], HFrEF, HFmrEF, and HFpEF were observed in 699 (60.8%), 122 (10.6%), and 328 (28.6%) patients, and 1 year mortality was 28.3%, 26.2%, and 20.1, respectively (log‐rank P = 0.036). As compared with HFrEF patients, HFpEF patients had a lower risk of all‐cause death [adjusted hazard ratio (HRadj) 0.67, 95% confidence interval (CI) 0.48–0.94, P = 0.022], whereas no difference was noted for HFmrEF patients. After multivariable adjustment, a lower risk of all‐cause death (HRadj for 5% increase 0.94, 95% CI 0.89–0.99, P = 0.017) and cardiovascular death (HRadj for 5% increase 0.94, 95% CI 0.88–1.00, P = 0.049) was observed at higher EF values. Beta‐blockers and renin–angiotensin system inhibitors or sacubitril/valsartan were associated with lower mortality in both EF

Abstract Background The predictive value of left ventricular (LV) global longitudinal strain (GLS) to predict outcomes in different left ventricular ejection fraction (LVEF) cohorts is not well known. We aimed to assess the role of LV GLS predicting outcomes in HF patients by LVEF. Methods In the Multicenter Automatic Defibrillator Implantation Trial Cardiac Resynchronization Therapy (MADIT‐CRT), we studied 1077 patients (59%) with 2D speckle tracking data available, 437 patients with LVEF > 30% and 640 with LVEF ≤ 30%. Baseline LV GLS was stratified in tertiles in both LVEF subgroups. The primary endpoint was ventricular tachycardia/fibrillation (VT/VF) or death; the secondary endpoint was heart failure (HF) or death. Results In patients with LVEF ≤ 30%, a higher tertile GLS (T3, less contractility) was associated with a higher rate of VT/VF/death (P 30% (P = 0.057). In patients with LVEF ≤ 30%, a higher tertile GLS was also associated with a higher rate of HF/death. In multivariable models, LV GLS predicted VT/VF or death in the LVEF ≤ 30% subgroup [T1 vs. T2/3 HR = 1.67 (1.16–2.38), P = 0.005], but not in those with LVEF > 30% [T1 vs. T2.3 HR = 1.32 (0.86–2.04), P = 0.21]. LV GLS predicted HF/death in the LVEF ≤ 30% subgroup [T1 vs T2/3 HR = 2.00 (1.30–3.13), P = 0.002], but not in in those with LVEF > 30%. Conclusions In this MADIT‐CRT sub‐study, LV GLS identified patients at higher risk of VT/VF, HF/death risk independently of conventional clinical parameters in patients with LVEF ≤ 30%, but not in patients with LVEF > 30%.

Background Left ventricular dysfunction is characterized by systolic and diastolic parameters, leading to heart failure (HF) with reduced or preserved ejection fraction (EF), respectively. The goal of this study is to examine the impact of left ventricular systolic and diastolic dysfunction (DD) on patient outcomes. Methods and Results Two cohorts were used in this analysis: Cohort A included 136 455 patients with EF ≥50%, stratified by the presence and grade of DD. Cohort B included 16 850 patients with EF

Abstract Titin‐dependent stiffening of cardiomyocytes is a significant contributor to left ventricular (LV) diastolic dysfunction in heart failure with preserved LV ejection fraction (HFpEF). Small heat shock proteins (HSPs), such as HSPB5 and HSPB1, protect titin and administration of HSPB5 in vitro lowers cardiomyocyte stiffness in pressure‐overload hypertrophy. In humans, oral treatment with geranylgeranylacetone (GGA) increases myocardial HSP expression, but the functional implications are unknown. Our objective was to investigate whether oral GGA treatment lowers cardiomyocyte stiffness and attenuates LV diastolic dysfunction in a rat model of the cardiometabolic syndrome. Twenty‐one‐week‐old male lean (n = 10) and obese (n = 20) ZSF1 rats were studied, and obese rats were randomized to receive GGA (200 mg/kg/day) or vehicle by oral gavage for 4 weeks. Echocardiography and cardiac catheterization were performed before sacrifice at 25 weeks of age. Titin‐based stiffness (Fpassive) was determined by force measurements in relaxing solution with 100 nM [Ca2+] in permeabilized cardiomyocytes at sarcomere lengths (SL) ranging from 1.8 to 2.4 μm. In obese ZSF1 rats, GGA reduced isovolumic relaxation time of the LV without affecting blood pressure, EF or LV weight. In cardiomyocytes, GGA increased myofilament‐bound HSPB5 and HSPB1 expression. Vehicle‐treated obese rats exhibited higher cardiomyocyte stiffness at all SLs compared to lean rats, while GGA reduced stiffness at SL 2.0 μm. In obese ZSF1 rats, oral GGA treatment improves cardiomyocyte stiffness by increasing myofilament‐bound HSPB1 and HSPB5. GGA could represent a potential novel therapy for the early stage of diastolic dysfunction in the cardiometabolic syndrome.

Background Heart failure with improved ejection fraction (EF) is increasingly recognized as a sizable and distinct entity. While the features associated with improvedEF have been explored and new guidelines have emerged, factors associated with sustaining an improved EF over time have not been defined. We aimed to assess factors associated with maintenance of an improved EF in a large real‐world patient cohort. Methods and Results A total of 7070 participants with heart failure with improved EF and a subsequent echocardiogram performed after at least 9 months of follow‐up were included in a retrospective cohort study conducted at the Cleveland Clinic in Cleveland, Ohio. Multiple logistic regression models, adjusted for demographics, comorbidities, and medications were built to identify characteristics and therapeutic interventions associated with maintaining an improved EF. Mean age (SD) was 64.9 (13.8) years, 62.7% were men, and 75.1% were White participants. White race and the use of angiotensin‐converting enzyme inhibitors, angiotensin receptor blockers, or angiotensin receptor–neprilysin inhibitors were associated with maintaining the EF at least 9 months after EF improvement. In contrast, male sex or having atrial fibrillation/flutter, coronary artery disease, history of myocardial infarction, presence of an implanted cardioverter‐defibrillator, and use of loop diuretics were associated with a decline in EF after previously documented improvement. Conclusions Continued use of renin–angiotensin–aldosterone system inhibitors was associated with maintaining the EF beyond the initial improvement phase.

Key Clinical Message Remimazolam is a new benzodiazepine sedative and has the characteristic of causing minimal effects on circulation. This case indicates that it can be considered as an option for anesthesia management of patients with decreased cardiac function. Abstract Some patients who undergo cardiac surgery have reduced cardiac function, which can often make anesthesia management difficult owing to severe hypotension at the time of anesthesia induction. Therefore, it is important to select drugs that cause minimal circulatory depression. On the other hand, in 2020, the use of remimazolam, a short‐acting benzodiazepine sedative, was approved in Japan, and reports of its use in various patients have been increasing. This drug has the characteristic of causing minimal effects on circulation. We here report the safe use of remimazolam in the anesthesia management of a patient with decreased cardiac function who was diagnosed as having angina pectoris. The patient was a 73‐year‐old man scheduled for coronary artery bypass graft (CABG) surgery. Remimazolam was used for sedation purposes during anesthesia induction. During surgery, there were no significant hemodynamic changes and the patient remained in stable cardiovascular condition. Our present case indicates that remimazolam can be considered as an option for anesthesia management in CABG for patients with decreased cardiac function.

Abstract Objective The aim of the study was to assess the efficacy of cardiac resynchronization therapy (CRT) in patients with chemotherapy‐induced cardiomyopathy (CIC). Methods With the increasing incidence of CIC, the association of CRT with improvement in clinical outcomes, echocardiographic parameters, and New York Heart Classification (NYHA) class was assessed through this qualitative systematic review. Results The five studies included a total of 169 patients who underwent CRT after CIC, and of these, 61 (36.1%) patients were males. All studies showed an improvement in left ventricular ejection fraction (LVEF), among other echocardiographic parameters of LV volume. However, these findings are limited by short follow‐up periods, small sample sizes, and the absence of a control group. Conclusion CRT was associated with improvement in all patient parameters with CIC.

Abstract Aims There are limited data about the relationship between body mass index (BMI) and left ventricular ejection fraction (EF) in patients with heart failure (HF). The study aims to assess the correlation between BMI and left ventricular EF under HF conditions. Methods and results We derived the data from the Dryad Digital Repository for analysis, and the information of the original patients was obtained from the MIMIC‐III database by the data uploader. We performed smooth curve and two piecewise linear regression analyses to evaluate the association between BMI and EF in HF patients. A total of 962 participants were included in this study, with age of 73.7 ± 13.5 years, and 475 participants were male (49.4%). The results of the smooth curve supported a U‐shaped relationship between BMI and EF, and the inflection point was found to be a BMI of 23.3 kg/m2 in these HF patients. After adjusting for potential confounders, we found that EF decreased with increasing BMI up to the inflection point (β = −0.7, 95% CI −1.3 to −0.1, P = 0.028), whereas beyond the turning point, the relationship between EF and BMI showed a positive correlation (β = 0.2, 95% CI 0.1–0.3 P

Abstract It remains unknown whether systolic (SBP) and diastolic (DBP) pressure on admission are associated with short‐ and long‐term mortality in Chinese patients with heart failure with preserved (HFpEF), mildly reduced (HFmrEF), and reduced (HFrEF) ejection fraction. In 2706 HF patients (39.1% women; mean age, 68.8 years), we assessed the risk of 30‐day, 1‐year, and long‐term (> 1 year) mortality with 1‐SD increment in SBP and DBP, using multivariable logistic and Cox regression, respectively. During a median follow‐up of 4.1 years, 1341 patients died. The 30‐day, 1‐year, and long‐term mortality were 3.5%, 16.7%, and 39.4%, respectively. In multivariable‐adjusted analyses additionally accounted for DBP or SBP, a higher SBP conferred a higher risk of long‐term mortality (hazard ratio, 1.11; 95% CI, 1.02‐1.22; p = .017) and a lower DBP was associated with a higher risk of all types of mortality (p ≤ .011) in all HF patients. Independent of potential confounders including DBP or SBP, in patients with HFpEF, higher SBP and lower DBP levels predicted a higher risk of long‐term mortality with hazard ratios amounting to 1.16 (95% CI, 1.04–1.29; p = .007) and .89 (95% CI, .80–.99; p = .028), respectively. In patients with HFmrEF and HFrEF, irrespective of adjustments of potential confounders, DBP was associated with 1‐year mortality with odds ratios ranging from .49 to .62 (p ≤ .006). In conclusion, lower DBP and higher SBP levels on admission were associated with a higher risk of different types of all‐cause mortality in Chinese patients with different HF subtypes. Our observations highlight that admission BP may help to improve risk stratification.

Abstract Aims Recent studies suggested that both left ventricular ejection fraction (LVEF) lower than 60% or higher than 65% were associated with an increased mortality in the general population. Uncertainty remains regarding adverse outcomes across LVEF in coronary artery disease (CAD). The common understanding was that LVEF 40%. We aimed to evaluate the relationship between LVEF and mortality or adverse events in CAD patients undergoing percutaneous coronary intervention (PCI). Methods and results A total of 10 252 CAD patients undergoing PCI from an observational cohort were studied. All‐cause mortality and major adverse cardiovascular and cerebrovascular events (MACCE) were set as outcomes. Kaplan–Meier curves, adjusted Cox regression models, and restricted cubic spline analyses were used for evaluation. A total of 137 (1.3%) patients had all‐cause mortality, and 816 (8.0%) patients had MACCE during a median of 2.4 years of follow‐up. The median LVEF was 64%. All‐cause mortality and MACCE rates changed substantially across LVEF categories, and a linear inverse relationship of LVEF with all‐cause mortality and MACCE risk was observed. All‐cause mortality or MACCE risk increased significantly below an LVEF of 55 or 65%, respectively. Patients with LVEF

Abstract Aims Duchenne muscular dystrophy (DMD) is an X‐linked recessive neuromuscular disorder, characterized by significant long‐term cardiac involvement. Dilated cardiomyopathy (DCM) is the main cause of death in DMD, and angiotensin‐converting enzyme inhibitors (ACEi) and beta‐blockers (BB) are first‐line treatments in DCM. It is unknown whether angiotensin receptor‐neprilysin inhibitor (ARNi) could provide greater benefits in this setting. Our aim is to assess whether ARNi use may prevent deterioration in ejection fraction (EF) or is associated with EF improvement compared with ACEi in DMD patients with heart failure and to report the tolerability of ARNi in this group of patients. Methods and results We followed 22 DMD patients, 6 of them with an EF 40%. The first group received ARNi on top of BB, while the control group started or continued first‐line therapy with ACEi ± BB. From December 2016 to December 2021, we recorded EF values at baseline and at follow‐up, comparing EF changes. Median follow‐up was 7 months (interquartile range 4.7–9.1). At baseline, the mean of EF (%) in the ARNi group was 31 ± 2%, while it was 59 ± 9% in the control group. At follow‐up, we recorded an EF improvement in the ARNi group (38 ± 6%, P‐value

Abstract Background Atrial septal shunt devices might improve hospitalizations and also prognosis in heart failure with increased pulmonary pressures due to left heart diseases. In recent years, atrial shunt devices have been used for the treatment of chronic heart failure, but there remains a lack of clinical experience. This study aimed to analyse the therapeutic effect of a novel type of atrial shunt on chronic heart failure. Methods and results From May 2020 to September 2020, six patients who were diagnosed with chronic heart failure and completed percutaneous D‐shant atrium shunt device implantation in the Department of Cardiovascular Surgery, Union Hospital, were retrospectively included. The shunt location was evaluated by echocardiography and digital subtraction angiography. Heart function was evaluated by New York Heart Association functional class. Echocardiography was used to measure the diameter of the new chamber and ventricle, and to evaluate the degree of mitral and tricuspid regurgitation. Before operation and 6 months after operation, left atrial end‐diastolic volume, right atrial end‐diastolic volume, left ventricular end‐diastolic volume, and right ventricular end‐diastolic volume were measured by magnetic resonance imaging. Left ventricular ejection fractions and right ventricular ejection fractions were calculated. Haemodynamic indexes of right heart catheterization and clinical cardiac function indexes were collected and compared before and 6 months after shunt implantation. All six patients completed percutaneous shunt device implantation. Echocardiography and digital subtraction angiography showed that the shunt device was correctly positioned and unobstructed in all patients. Echocardiography revealed that the left ventricular diameter decreased significantly from 6.40 ± 0.57 mm to 5.03 ± 0.73 mm (P

Background Many patients with heart failure (HF) have severely reduced ejection fraction but do not meet threshold for consideration of advanced therapies (ie, stage D HF). The clinical profile and health care costs associated with these patients in US practice is not well described. Methods and Results We examined patients hospitalized for worsening chronic heart failure with reduced ejection fraction ≤40% from 2014 to 2019 in the GWTG‐HF (Get With The Guidelines‐Heart Failure) registry, who did not receive advanced HF therapies or have end‐stage kidney disease. Patients with severely reduced EF defined as EF ≤30% were compared with those with EF 31% to 40% in terms of clinical profile and guideline‐directed medical therapy. Among Medicare beneficiaries, postdischarge outcomes and health care expenditure were compared. Among 113 348 patients with EF ≤40%, 69% (78 589) had an EF ≤30%. Patients with severely reduced EF ≤30% tended to be younger and were more likely to be Black. Patients with EF ≤30% also tended to have fewer comorbidities and were more likely to be prescribed guideline‐directed medical therapy (“triple therapy” 28.3% versus 18.2%, P

Abstract Objective Stoke after revascularization including both percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) is an uncommon but devastating complication. Patients with reduced ejection fraction (EF) had an increased risk of stroke after revascularization. However, little is known about the determinants and outcomes of stroke among patients with reduced EF following revascularization. Materials and Methods A cohort study of patients with preoperative reduced EF (≤40%) who received revascularization by either PCI or CABG between January 1, 2005 and December 31, 2014 was performed. Multivariate logistic regression was used to identify independent correlates of stroke. Logistic regression models were applied to evaluate the association of stroke with clinical outcomes. Results A total of 1937 patients were enrolled in this study. Of these, 111 (5.7%) patients suffered from stroke during the median 3.5‐year follow‐up. Older age (odds ratio [OR], 1.03; 95% CI, 1.01–1.05; p = .009), history of hypertension (OR, 1.79; 95% CI, 1.18–2.73; p = .007), and history of stroke (OR, 2.00; 95% CI, 1.19–3.36; p = .008) were found to be independent predictors for stroke. Patients with and without stroke had similar risk of all‐cause death (OR, 0.91; 95% CI, 0.59–1.41; p = .670). However, stroke was associated with higher odds ratio of heart failure (HF) hospitalization (OR, 2.77; 95% CI, 1.74–4.40; p

Abstract Aims We hypothesized that left atrial (LA) remodelling and function are associated with poor exercise capacity as prognostic marker in chronic heart failure (CHF) across a broad range of left ventricular ejection fraction (LVEF). Methods and results One hundred seventy‐one patients with CHF were analysed [age 65 ± 11 years, 136 males (80%); 86 heart failure with reduced ejection fraction (HFrEF), 27 heart failure with mid‐range ejection fraction (HFmrEF), 58 heart failure with preserved ejection fraction (HFpEF)]. All patients underwent echocardiography and maximal cardiopulmonary exercise testing and were classified according to a prognostic cut‐off of peak VO2 (pVO2; 14 mL/kg/min). Seventy‐seven (45%) patients reached pVO2

Abstract Aim Echo‐derived haemodynamic classification, based on forward‐flow and left ventricular (LV) filling pressure (LVFP) correlates, has been proposed to phenotype patients with heart failure and reduced ejection fraction (HFrEF). To assess the prognostic relevance of baseline echocardiographically defined haemodynamic profile in ambulatory HFrEF patients before starting sacubitril/valsartan. Methods and results In our multicentre, open‐label study, HFrEF outpatients were classified into 4 groups according to the combination of forward flow (cardiac index; CI:< or ≥2.0 L/min/m2) and early transmitral Doppler velocity/early diastolic annular velocity ratio (E/e′: ≥ or

Abstract Aims A method for estimating right ventricular ejection fraction (RVEF) from RV pressure waveforms was recently validated in an experimental model. Currently, cardiac magnetic resonance imaging (MRI) is the clinical reference standard for measurement of RVEF in pulmonary arterial hypertension (PAH). The present study was designed to test the hypothesis that the pressure‐based method can detect clinically significant reductions in RVEF as determined by cardiac MRI in patients with PAH. Methods and results RVEF estimates derived from analysis of RV pressure waveforms recorded during right heart catheterization (RHC) in 25 patients were compared with cardiac MRI measurements of RVEF obtained within 24 h. Three investigators blinded to cardiac MRI results independently performed pressure‐based RVEF estimation with the mean of their results used for comparison. Linear regression was used to assess correlation, and a receiver operator characteristic (ROC) curve was derived to define ability of the pressure‐based method to detect a maladaptive RV response, defined as RVEF

Abstract Heart failure with recovered ejection fraction (HFrecEF) involves those who have previously had reduced cardiac function that has subsequently improved. However, there is not a single definition of this phenomenon and recovery of cardiac function in terms of left ventricular ejection fraction (LVEF) itself does not necessarily correlate with remission from the detrimental physiology of heart failure (HF) and its consequences. There is also the question of the utility of defibrillators in these patients, and whether they should be replaced at the time of battery depletion. To address this, several studies have shown specific predictors of ensuing LVEF recovery, including patient demographics, co‐morbidities, and medication use, as well as predictors of ventricular arrhythmias (VA) following LVEF recovery. Recent studies have also shown novel imaging parameters that may aid in predicting which patients would have a higher risk of these arrhythmias. Additional data describe a small, yet appreciable risk of VA, in addition to appropriate shocks as well. In this review, we describe predictors of LVEF recovery, carefully analyse and characterize the continued risk for VA and appropriate shocks following LVEF recovery, and explore additional novel modalities that may aid in decision‐making.

Abstract Aims The aim of this study was to evaluate the prognostic value of feature tracking (FT) derived cardiac magnetic resonance (CMR) strain parameters of the left ventricle (LV)/right ventricle (RV) in ischaemic cardiomyopathy (ICM) patients treated with an implantable cardioverter‐defibrillator (ICD). Current guidelines suggest a LV‐ejection fraction ≤35% as major criterion for ICD implantation in ICM, but this is a poor predictor for arrhythmic events. Supplementary parameters are missing. Methods and results Ischaemic cardiomyopathy patients (n = 242), who underwent CMR imaging prior to primary and secondary implantation of ICD, were classified depending on EF ≤ 35% (n = 188) or >35% (n = 54). FT parameters were derived from steady‐state free precession cine views using dedicated software. The primary endpoint was a composite of cardiovascular mortality (CVM) and/or appropriate ICD therapy. There were no significant differences in FT‐function or LV‐/RV‐function parameters in patients with an EF ≤ 35% correlating to the primary endpoint. In patients with EF > 35%, standard CMR functional parameters, such as LV‐EF, did not reveal significant differences. However, significant differences in most FT parameters correlating to the primary endpoint were observed in this subgroup. LV‐GLS (left ventricular‐global longitudinal strain) and RV‐GRS (right ventricular‐global radial strain) revealed the best diagnostic performance in ROC curve analysis. The combination of LV‐GLS and RV‐GRS showed a sensitivity of 85% and a specificity of 76% for the prediction of future events. Conclusions The impact of FT derived measurements in the risk stratification of patients with ICM depends on LV function. The combination of LV‐GLS/RV‐GRS seems to be a predictor of cardiovascular mortality and/or appropriate ICD therapy in patients with EF > 35%.

Abstract Aims Chronic heart failure with reduced ejection fraction remains a major health issue. To date, no reliable biomarker is available to predict reduced left ventricular ejection fraction (LV‐EF). We aimed to identify novel circulating biomarkers for reduced left ventricular function using untargeted serum metabolomics in two independent patient cohorts. Methods and results Echocardiography and non‐targeted serum metabolomics were conducted in two patient cohorts with varying left ventricular function: (1) 25 patients with type 2 diabetes with established cardiovascular disease or high cardiovascular risk (LV‐EF range 20–66%) (discovery cohort) and (2) 37 patients hospitalized for myocardial infarction (LV‐EF range 25–60%) (validation cohort). In the discovery cohort, untargeted metabolomics revealed seven metabolites performing better than N‐terminal pro‐B‐type natriuretic peptide in the prediction of impaired left ventricular function shown by LV‐EF. For only one of the metabolites, acisoga, the predictive value for LV‐EF could be confirmed in the validation cohort (r = −0.37, P = 0.02). In the discovery cohort, acisoga did not only correlate with LV‐EF (r = −60, P = 0.0016), but also with global circumferential strain (r = 0.67, P = 0.0003) and global longitudinal strain (r = 0.68, P = 0.0002). Similar results could be detected in the discovery cohort in a 6 month follow‐up proofing stability of these results over time. With an area under the curve of 0.86 in the receiver operating characteristic analysis, acisoga discriminated between patients with normal EF and LV‐EF

Background Inflammatory cardiomyopathy is one of the most common causes of sudden cardiac death in young adults. Diagnosis of inflammatory cardiomyopathy remains challenging, and better monitoring tools are needed. We present magnetocardiography as a method to diagnose myocardial inflammation and monitor treatment response. Methods and Results A total of 233 patients were enrolled, with a mean age of 45 (±18) years, and 105 (45%) were women. The primary analysis included 209 adult subjects, of whom 66 (32%) were diagnosed with inflammatory cardiomyopathy, 17 (8%) were diagnosed with cardiac amyloidosis, and 35 (17%) were diagnosed with other types of nonischemic cardiomyopathy; 91 (44%) did not have cardiomyopathy. The second analysis included 13 patients with inflammatory cardiomyopathy who underwent immunosuppressive therapy after baseline magnetocardiography measurement. Finally, diagnostic accuracy of magnetocardiography was tested in 3 independent cohorts (total n=23) and 1 patient, who developed vaccine‐related myocarditis. First, we identified a magnetocardiography vector to differentiate between patients with cardiomyopathy versus patients without cardiomyopathy (vector of ≥0.051; sensitivity, 0.59; specificity, 0.95; positive predictive value, 93%; and negative predictive value, 64%). All patients with inflammatory cardiomyopathy, including a patient with mRNA vaccine‐related myocarditis, had a magnetocardiography vector ≥0.051. Second, we evaluated the ability of the magnetocardiography vector to reflect treatment response. We observed a decrease of the pathologic magnetocardiography vector toward normal in all 13 patients who were clinically improving under immunosuppressive therapy. Magnetocardiography detected treatment response as early as day 7, whereas echocardiographic detection of treatment response occurred after 1 month. The magnetocardiography vector decreased from 0.10 at baseline to 0.07 within 7 days (P=0.010) and to 0.03 within 30 days (P

Abstract Aim While sympathetic overactivity in heart failure (HF) with reduced ejection fraction (HFrEF; EF

Aims: Glucagon-like peptide-1 receptor agonists reduce major adverse cardiovascular events (MACE) and cardiovascular mortality in people with type 2 diabetes (T2D). However, previous studies suggest the effects on heart failure outcomes vary according to left ventricular ejection fraction (LVEF). We aimed to evaluate the effects of exenatide on cardiovascular events according to LVEF in people with T2D., Methods and Results: Post-hoc analysis of the Exenatide Study of Cardiovascular Event Lowering (EXSCEL) trial evaluating the effects of once-weekly exenatide (EQW) versus placebo on cardiovascular outcomes according to baseline LVEF (<40% or ≥40%). Outcomes were also evaluated according to New York Heart Association (NYHA) class and obesity. The main outcome was hospitalization for heart failure (HHF). A treatment-by-LVEF interaction was used. In EXSCEL (n = 14 752), 4749 participants had LVEF available at baseline; 455 (10%) with LVEF <40%, 4294 (90%) with LVEF ≥40%. LVEF modified the EQW effect on hHF: hazard ratio (HR) = 1.52 (95% confidence interval [CI] = 0.95-2.43) in participants with LVEF < 40% and HR = 0.74 (95% CI = 0.55-1.01) in those with LVEF ≥ 40% (p-interaction = 0.012). No significant treatment-by-LVEF interactions (p-interaction >0.10) were observed for MACE, cardiovascular death or all-cause mortality. The risk of HHF was also modified by baseline NYHA class (HR 0.91, 95% CI 0.65-1.27 for NYHA class I/II; HR 1.84, 95% CI 0.95-3.59 for NYHA class III/IV; p-interaction = 0.062), mostly driven by the LVEF <40% subgroup. Obesity did not modify the effects of EQW on HHF., Conclusions: The EQW effect on HHF was influenced by LVEF, with a potentially decreased risk in participants with LVEF ≥40% and increased risk in those with LVEF <40%. The risk of HHF was particularly high in participants with LVEF <40% and NYHA class III/IV. LVEF did not modify the effect of EQW on atherosclerotic outcomes., (© 2024 European Society of Cardiology.)

Aims: We analysed baseline characteristics and guideline-directed medical therapy (GDMT) use and decisions in the European Society of Cardiology (ESC) Heart Failure (HF) III Registry., Methods and Results: Between 1 November 2018 and 31 December 2020, 10 162 patients with acute HF (AHF, 39%, age 70 [62-79], 36% women) or outpatient visit for HF (61%, age 66 [58-75], 33% women), with HF with reduced (HFrEF, 57%), mildly reduced (HFmrEF, 17%) or preserved (HFpEF, 26%) ejection fraction were enrolled from 220 centres in 41 European or ESC-affiliated countries. With AHF, 97% were hospitalized, 2.2% received intravenous treatment in the emergency department, and 0.9% received intravenous treatment in an outpatient clinic. AHF was seen by most by a general cardiologist (51%) and outpatient HF most by a HF specialist (48%). A majority had been hospitalized for HF before, but 26% of AHF and 6.1% of outpatient HF had de novo HF. Baseline use, initiation and discontinuation of GDMT varied according to AHF versus outpatient HF, de novo versus pre-existing HF, and by ejection fraction. After the AHF event or outpatient HF visit, use of any renin-angiotensin system inhibitor, angiotensin receptor-neprilysin inhibitor, beta-blocker, mineralocorticoid receptor antagonist and loop diuretics was 89%, 29%, 92%, 78%, and 85% in HFrEF; 89%, 9.7%, 90%, 64%, and 81% in HFmrEF; and 77%, 3.1%, 80%, 48%, and 80% in HFpEF., Conclusion: Use and initiation of GDMT was high in cardiology centres in Europe, compared to previous reports from cohorts and registries including more primary care and general medicine and regions more local or outside of Europe and ESC-affiliated countries., (© 2024 European Society of Cardiology.)

Background Heart failure (HF) has a dramatic impact on worldwide health care systems that is determined by the growing prevalence of and the high exposure to cardiovascular and noncardiovascular events. Prognosis remains poor. We sought to compare a large population with HF across the ejection fraction (EF) spectrum with a population without HF for patient characteristics, and HF, cardiovascular, and noncardiovascular outcomes. Methods and Results Patients with HF registered in the Swedish HF registry in 2005 to 2018 were compared 1:3 with a sex‐, age‐, and county‐matched population without HF. Outcomes were cardiovascular and noncardiovascular mortality and hospitalizations. Of 76 453 patients with HF, 53% had reduced EF, 23% mildly reduced EF, and 24% preserved EF. Compared with those without HF, patients with HF had more cardiovascular and noncardiovascular comorbidities and worse socioeconomic status. Incidence of cardiovascular and noncardiovascular events was higher in people with HF versus non‐HF, with increased risk of all‐cause (hazard ratio [HR], 2.53 [95% CI, 2.50–2.56]), cardiovascular (HR, 4.67 [95% CI, 4.59–4.76]), and noncardiovascular (HR, 1.49 [95% CI, 1.46–1.52]) mortality, 2‐ to 5‐fold higher risk of first/repeated cardiovascular and noncardiovascular hospitalizations, and ~4 times longer in‐hospital length of stay for any cause. Patients with HF with reduced EF had higher risk of HF hospitalizations, whereas those with HF with preserved EF had higher risk of all‐cause and noncardiovascular hospitalization and mortality. Conclusions Patients with HF exert a high health care burden, with a much higher risk of cardiovascular, all‐cause, and noncardiovascular events, and nearly 4 times as many days spent in hospital compared with those without HF. These epidemiological data may enable strategies for optimal resource allocation and HF trial design.

Abstract Aims The aim of this study is to investigate the prognostic implications of the presence of heart failure (HF) across the range of left ventricular ejection fraction (LVEF) in patients with comorbid atrial fibrillation (AF). Methods and results We conducted a retrospective cohort study of 1063 patients (median age 76 years), discharged from the cardiology ward with a primary or secondary diagnosis of AF between 2015 and 2018. We used Cox proportional‐hazards and spline models to examine the association of the presence of HF, across the range of LVEF, with the primary outcome of all‐cause mortality. HF was documented in 52.9% of patients at baseline. During a median follow‐up of 31 months (interquartile range 10 to 52 months), 37.3% of patients died. The presence of HF was associated with a significantly higher risk of mortality [adjusted hazard ratio (aHR) 2.17; 95% confidence interval (CI), 1.70 to 2.77; P

Abstract Aims Heart failure (HF) guidelines place patients into 3 discrete groups according to left ventricular ejection fraction (LVEF): reduced (

Abstract Aims This study aimed to elucidate the risk for stroke and systemic embolism (SE) in patients with atrial fibrillation and heart failure (HF) according to HF type. Methods and results A total of 10 780 patients with atrial fibrillation were enrolled in a multicentre prospective registry and divided according to HF type: no‐HF, HF with preserved ejection fraction (EF) (HFpEF), HF with mid‐range EF (HFmrEF), and HF with reduced EF (HFrEF). Each group included 237 age‐matched and sex‐matched patients (age, 69.0 ± 10.3 years; men, 69.6%). The baseline characteristics, cumulative incidence, and hazard ratios for stroke/SE and major bleeding were compared across the groups. Patients with HF accounted for 10.3% of the total population; HFpEF, HFmrEF, and HFrEF represented 43.7%, 23.6%, and 32.7% of the patients with HF, respectively. The CHA2DS2‐VASc score was significantly higher in the HFpEF, HFmrEF, and HFrEF groups than in the no‐HF group. The annual stroke/SE incidence rates were 2.8%, 0.7%, 1.1%, and 0.9% in the HFpEF, HFmrEF, HFrEF, and no‐HF groups, respectively. The cumulative incidence of stroke/SE was significantly highest in the HFpEF group at 22.8 ± 10.0 months (P = 0.020). The stroke/SE risk was higher in the HFpEF group than in the HFmrEF and HFrEF groups (hazard ratio, 3.192; 95% confidence interval, 1.039–9.810; P = 0.043). E/e' value was an independent risk factor for stroke/SE. There were no significant differences in the incidence of major bleeding across the groups. Conclusions The stroke/SE risk was the highest in the HFpEF group and comparable between the HFmrEF and HFrEF groups.

Abstract Background Sex‐specific differences in left ventricular ejection fraction (LVEF) and responses to neurohormonal modulating therapies are relevant to clinical trials of treatment for heart failure with preserved ejection fraction (HFpEF). Aims This study aimed to identify the proportion and characteristics of patients presenting with possible or confirmed HFpEF within the National Echo Database of Australia. Results A total of 237 046 women (48.1%) and 256 019 men (aged 61.0 ± 18.3 vs. 60.6 ± 17.1 years, respectively) had sex‐specific distributions of LVEF: 94.3% of women had LVEF ≥ 45% (mean LVEF 66.0 ± 8.6%), compared with 87.2% of men (mean LVEF 63.4 ± 8.7%). The presence of structural heart disease (SHD) according to the PARAGON‐HF criteria could be calculated in 93.8% of women and 93.4% of men with an LVEF ≥ 45%. Of these, 64 502 (30.8%) women and 104 344 (50.0%) of men had left ventricular hypertrophy, and 78 948 (35.3%) and 95 846 (42.9%), respectively, had left atrial enlargement. As a result, the proportion of women vs. men fulfilling echocardiographic criteria for HFpEF was very different: 111 497 (53.2%) vs. 146 359 (70.1%). SHD markedly increased with age, associated with a greater increase in women than men. The same signal was observed in those referred for suspected or previously confirmed HFpEF. Conclusions Double the number of men than women had LVEF

Abstract Aims Limited data are available on clinical characteristics and prognosis of heart failure (HF) in black African populations especially with respect to current classifications and HF management guidelines. Methods and results In this post hoc analysis, African patients admitted with acute HF and enrolled in the THESUS‐HF registry in one of 12 hospitals in 9 countries were classified as having preserved left ventricular ejection fraction (LVEF) (HFpEF), mid‐range LVEF (HFmrEF), and reduced LVEF (HFrEF) based on echocardiography performed close to the time of admission. Sociodemographic and clinical characteristics, management, and 60 and 180 day outcomes were compared between the groups. Of 888 patients with LVEF available, there were 472 (53.2%) with HFrEF, 174 (19.6%) with HFmrEF, and 243 (27.3%) with HFpEF. History of atrial fibrillation was higher in patients with HFmrEF (28.5%) than in patients with HFrEF (14.5%). Patients with HFrEF had a larger mean LV systolic diameter (54.1 ± 9.67 mm) than patients with HFmrEF (42.9 ± 8.47 mm), who had a larger mean LV diameter than patients with HFpEF (32.6 ± 8.64 mm); a similar pattern with LV diastolic diameter was observed. The mean posterior diastolic wall thickness (10.2 ± 2.94 mm) was lower in patients with HFrEF than in those with HFmrEF (11.1 ± 2.59 mm) and HFpEF (11.2 ± 2.90 mm). Patients with HFpEF were less likely to use angiotensin‐converting enzyme inhibitor/angiotensin receptor blockers, and aldosterone inhibitors, and more likely to use beta‐blockers than those with HFrEF at either admission or discharge/Day 7. Death or readmission rates through Day 60 and 180 day death rates did not differ significantly among the groups; unadjusted hazard ratios relative to patients with HFrEF were 1.32 [95% confidence interval (CI) 0.84–2.08] and 1.24 (95% CI 0.82–1.89) for 60 day death or readmission and 0.92 (95% CI 0.59–1.43) and 0.78 (95% CI 0.51–1.20) for 180 day death in patients with HFmrEF and HFpEF, respectively. Conclusions Classification by LVEF according to European Society of Cardiology guidelines revealed some differences in clinical presentation but similar mortality and rehospitalization rates across all EF groups in Africans admitted for HF.

Abstract Aims This study aimed to investigate whether the risk of short‐term mortality is different in pulmonary embolism (PE) patients who have heart failure with reduced ejection fraction (HFrEF) as compared with those with heart failure with preserved ejection fraction (HFpEF). Methods and results Predictive value of HFrEF or HFpEF for 7‐day (intrahospital) and 30‐day all‐cause mortality was determined in the cohort of 1055 out of 1201 consecutive acute PE patients from the Serbian multicentre PE registry. Patients were classified into either HFrEF or HFpEF group, according to guideline‐proposed criteria. A 7‐day (intrahospital) and 30‐day all‐cause mortality was 18.5% vs. 7.3% vs. 4.5% (P

Abstract Type 2 diabetes (T2D) affects >30 million Americans and nearly 70% of individuals with T2D will die from cardiovascular disease (CVD). Circulating levels of the inflammatory signaling lipid, prostaglandin E2 (PGE2), are elevated in the setting of obesity and T2D and are associated with decreased cardiac function. The EP3 and EP4 PGE2 receptors have opposing actions in several tissues, including the heart: overexpression of EP3 in cardiomyocytes impairs function, while EP4 overexpression improves function. Here we performed complementary studies in vitro with isolated cardiomyocytes and in vivo using db/db mice, a model of T2D, to analyze the effects of EP3 inhibition or EP4 activation on cardiac function. Using echocardiography, we found that 2 weeks of systemic treatment of db/db mice with 20 mg/kg of EP3 antagonist, beginning at 6 weeks of age, improves ejection fraction and fractional shortening (with no effect on heart rate). We further show that either EP3 blockade or EP4 activation enhances contractility and calcium cycling in isolated mouse cardiomyocytes cultured in both normal and high glucose. Thus, peak [Ca2+]I transient amplitude was increased, while time to peak [Ca2+]I and [Ca2+]I decay were decreased. These data suggest that modulation of EP3 and EP4 activity has beneficial effects on cardiomyocyte contractility and overall heart function.

Abstract Aims Acute heart failure (AHF) leads to a drastic increase in mortality and rehospitalization. The aim of the study was to identify prognostic variables in a real‐life population of AHF patients admitted to the emergency department with acute shortness of breath. Methods and results We evaluated potential predictors of mortality in 728 consecutive patients admitted to the emergency department with AHF. Possible predictors of all‐cause and cardiovascular (CV) mortality were investigated by Cox and Fine and Gray models at multivariable analysis. Among the 728 patients, 256 died during the entire follow‐up, 142 of these due to CV cause. The 1 year mortality rate was 20%, with the highest risk of death during the index hospitalization (with 8% estimate in‐hospital mortality at 30 days). A higher risk of events during the index hospitalization was more evident for the CV deaths, for which we found a cumulative 1 year incidence of 12% with a cumulative incidence in the first 30 days of hospitalization of about 5%. At multivariable analysis, age (P

Abstract Aims Left ventricular ejection fraction (EF) is required to categorize heart failure (HF) [i.e. HF with preserved (HFpEF), mid‐range (HFmrEF), and reduced (HFrEF) EF] but is often not captured in population‐based cohorts or non‐HF registries. The aim was to create an algorithm that identifies EF subphenotypes for research purposes. Methods and results We included 42 061 HF patients from the Swedish Heart Failure Registry. As primary analysis, we performed two logistic regression models including 22 variables to predict (i) EF≥ vs.

Abstract Background Long‐term use of doxorubicin (DOX) is limited by cumulative dose‐dependent cardiotoxicity. Objectives Identify plasma extracellular vesicle (EV)‐associated microRNAs (miRNAs) as a biomarker for cardiotoxicity in dogs by correlating changes with cardiac troponin I (cTnI) concentrations and, echocardiographic and histologic findings. Animals Prospective study of 9 client‐owned dogs diagnosed with sarcoma and receiving DOX single‐agent chemotherapy (total of 5 DOX treatments). Dogs with clinically relevant metastatic disease, preexisting heart disease, or breeds predisposed to cardiomyopathy were excluded. Methods Serum concentration of cTnI was monitored before each treatment and 1 month after the treatment completion. Echocardiography was performed before treatments 1, 3, 5, and 1 month after completion. The EV‐miRNA was isolated and sequenced before treatments 1 and 3, and 1 month after completion. Results Linear mixed model analysis for repeated measurements was used to evaluate the effect of DOX. The miR‐107 (P = .03) and miR‐146a (P = .02) were significantly downregulated whereas miR‐502 (P = .02) was upregulated. Changes in miR‐502 were significant before administration of the third chemotherapeutic dose. When stratifying miRNA expression for change in left ventricular ejection fraction, upregulation of miR‐181d was noted (P = .01). Serum concentration of cTnI changed significantly but only 1 month after treatment completion, and concentrations correlated with left ventricular ejection fraction and left ventricular internal dimension in diastole. Conclusion and Clinical Significance Downregulation of miR‐502 was detected before significant changes in cTnI concentrations or echocardiographic parameters. Further validation using a larger sample size will be required.

Abstract Aim Long‐term outcome data of acute decompensated heart failure (HF) are scarce from India. The aim of the study was to collect in‐hospital and long‐term outcome data of HF patients admitted during 2001–2010 in a tertiary‐care centre in South India. Methods and results Consecutive patients admitted with first episode of decompensated HF were part of the registry. Data regarding diagnosis, risk factors, treatment, early (in‐hospital), and late (5 and 10year) mortality outcomes were captured. During this period, 1502 patients were admitted with first episode of decompensated HF [37.7% of women, mean age of 51.1 (SD = 14.3) years]. Common causes were ischaemic heart disease (36.2%), rheumatic heart disease (34.3%), and cardiomyopathies (9.9%). HF with reduced ejection fraction (HFrEF) was present in 26.9% of patients, and 33.8% had atrial arrhythmias. Diabetes, hypertension, and renal dysfunction were prevalent in 27.4%, 28.6%, and 37.4%, respectively. Median duration of hospitalization was 6 days (interquartile range: 3–10), and 247 patients (16.4%) died during index admission. The total time at risk was 6248 person years, and 1051 patients died during the study period with a median survival time of 3.7 years. Overall mortality rate was 16.8 per 100 person years (95% CI: 15.8–17.9 per 100 person years). Older age [hazard ratio (HR) = 1.08, 95% CI: 1.02–1.14, P = 0.007], anaemia (HR = 1.34, 95% CI: 1.08–1.65, P = 0.007), renal dysfunction (HR = 1.38, 95% CI: 1.20–1.59, P < 0.001), HFpEF (HR = 0.61, 95% CI: 0.52–0.73, P < 0.001 against HFrEF), and the use of guideline‐directed therapies (GDT; beta blockers: HR = 0.57, 95% CI: 0.49–0.66, P < 0.0001; and angiotensin converting enzyme inhibitor/angiotensin receptor blocker: HR = 0.59, 95% CI: 0.51–0.69, P < 0.001) were important predictors of mortality. Patients with HF and mid‐range EF also benefited from GDT. Conclusion In our cohort, ischaemic and rheumatic heart diseases were the leading contributors for HF. Anaemia, renal dysfunction, poor ejection fraction, and suboptimal prescriptions of GDT were the main predictors of long‐term mortality. Both patients with HFrEF and mid‐range EF benefited from GDT.

Background Myocardial strain can identify subclinical left ventricular dysfunction in various cardiac diseases, but its association with clinical outcomes in genetic cardiomyopathies remains unknown. Herein, we assessed myocardial strain in patients with Danon disease (DD), a rare X‐linked autophagic disorder that causes severe cardiac manifestations. Methods and Results Echocardiographic images were reviewed and used to calculate myocardial strain from a retrospective, international registry of patients with DD. Regression analyses were performed to evaluate for an association of global longitudinal strain (GLS) and ejection fraction with the composite outcome (death, ventricular assist device, heart transplantation, and implantable cardioverter defibrillator for secondary prevention). A total of 22 patients with DD (male 14 [63.6%], median age 16.5 years) had sufficient echocardiograms for analysis. Absolute GLS was reduced with a mean of 12.2% with an apical‐sparing pattern observed. Univariable regression for GLS and composite outcome showed an odds ratio of 1.32 (95% CI, 1.02–1.71) with P=0.03. For receiver operating characteristic analysis, the areas under the curve for GLS and ejection fraction were 0.810 (P=0.02) and 0.605 (P=0.44), respectively. An absolute GLS cutoff of 10.0% yielded a true positive rate of 85.7% and false positive rate of 13.3%. Conclusions In this cohort of patients with DD, GLS may be a useful assessment of myocardial function and may predict clinical outcomes. This study highlights the potential use of myocardial strain phenotyping to monitor disease progression and potentially to predict clinical outcomes in DD and other genetic cardiomyopathies.

Background Data on rehospitalizations for heart failure (HF) in Asia are scarce. We sought to determine the burden and predictors of HF (first and recurrent) rehospitalizations and all‐cause mortality in patients with HF and preserved versus reduced ejection fraction (preserved EF, ≥50%; reduced EF,

Background This study was designed to investigate the genetic evidence for repurposing of GLP1R (glucagon‐like peptide‐1 receptor) agonists to prevent heart failure (HF) and whether the potential benefit exceeds the benefit conferred by more general glycemic control. Methods and Results We applied 2‐sample Mendelian randomization of genetically proxied GLP1R agonism on HF as the main outcome and left ventricular ejection fraction as the secondary outcome. The associations were compared with those of general glycemic control on the same outcomes. Genetic associations were obtained from genome‐wide association study summary statistics of type 2 diabetes mellitus (228 499 cases and 1 178 783 controls), glycated hemoglobin (n=344 182), HF (47,309 cases and 930 014 controls), and left ventricular ejection fraction (n=16 923). Genetic proxies for GLP1R agonism associated with reduced risk of HF (odds ratio per 1 mmol/mol decrease in glycated hemoglobin 0.75; 95% CI, 0.64–0.87; P=1.69×10−4), and higher left ventricular ejection fraction (SD change in left ventricular ejection fraction per 1 mmol/mol decrease in glycated hemoglobin 0.22%; 95% CI, 0.03–0.42; P=0.03). The magnitude of these benefits exceeded those expected from improved glycemic control more generally. The results were similar in sensitivity analyses, and we did not find evidence to suggest that these associations were mediated by reduced coronary artery disease risk. Conclusions This genetic evidence supports the repurposing of GLP1R agonists for preventing HF.

Abstract Background Broadly applicable reference intervals (RIs) for measurements of left atrial (LA) and left ventricular (LV) size and function generated prospectively using statistically appropriate methods are limited. Objectives To generate body size‐independent RIs for linear, area, and volume measurements of LA size and LV size and function. Animals Healthy adult dogs (n = 122) of variable size and somatotype. Methods Prospective study. All dogs underwent an echocardiogram performed by the same examiner. Effects of body weight, sex, age, and heart rate were evaluated by regression and correlation analyses. Scaling exponents and prediction intervals were generated for linear measurements using the allometric equation. After normalization to body weight, 95% RIs were determined using nonparametric methods with 2.5 and 97.5 percentiles serving as the lower and upper limits (each with 90% confidence intervals), respectively. Results Linear LA and LV measurements were strongly correlated (R2 ≥ 0.79) with body weight. Scaling exponents were close to the expected 1/3 (0.299‐0.392). Prediction intervals for linear measurements of LV chamber size were considerably narrower than previously reported. Weak correlations (r = −0.42 to −0.50) among LV fractional shortening, fractional area change, and ejection fraction and body weight were identified. No other meaningful relationships were identified between the measurements and sex, age, and heart rate. Conclusions and Clinical Importance Body size‐independent RIs for several linear, area, and volume measurements of LA and LV size and function were generated prospectively from a large and diverse reference population and are available for clinical use.

Background Chronic obstructive pulmonary disease (COPD) is a common comorbidity in heart failure with reduced ejection fraction, associated with undertreatment and worse outcomes. New treatments for heart failure with reduced ejection fraction may be particularly important in patients with concomitant COPD. Methods and Results We examined outcomes in 8399 patients with heart failure with reduced ejection fraction, according to COPD status, in the PARADIGM‐HF (Prospective Comparison of Angiotensin Receptor Blocker–Neprilysin Inhibitor With Angiotensin‐Converting Enzyme Inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure) trial. Cox regression models were used to compare COPD versus non‐COPD subgroups and the effects of sacubitril/valsartan versus enalapril. Patients with COPD (n=1080, 12.9%) were older than patients without COPD (mean 67 versus 63 years; P

Background The prognosis of left ventricular noncompaction (LVNC) remains elusive despite its recognition as a clinical entity for >30 years. We sought to identify clinical and imaging characteristics and risk factors for mortality in patients with LVNC. Methods and Results 339 adults with LVNC seen between 2000 and 2016 were identified. LVNC was defined as end‐systolic noncompacted to compacted myocardial ratio >2 (Jenni criteria) and end‐diastolic trough of trabeculation‐to‐epicardium (X):peak of trabeculation‐to‐epicardium (Y) ratio 2.3 (Petersen criteria) by magnetic resonance imaging. Median age was 47.4 years, and 46% of patients were female. Left ventricular ejection fraction

Aim: To assess cause-specific death in patients with heart failure with preserved, mildly reduced, and reduced ejection fraction (HFpEF, HFmrEF, and HFrEF)., Methods and Results: Data were analysed from the Swedish Heart Failure Registry (SwedeHF) and the National Patient Register of patients enrolled in SwedeHF 2000-2021. Cox proportional hazards regression models were performed and adjusted for age, sex and time period. Among 100 584 patients (23% HFpEF, 23% HFmrEF, 53% HFrEF), median age (interquartile range) was 75 (66-82) and 36% were female. Of those who died within 5 years, most deaths were ascribed to cardiovascular (CV) causes across all ejection fraction (EF) categories. Within 5 years, HFpEF had higher adjusted risk of non-CV death (hazard ratio [HR] 1.33, 95% confidence interval [CI] 1.28-1.38, p < 0.001) and lower adjusted risk of CV death (HR 0.85, 95% CI 0.82-0.88, p < 0.001) compared to HFrEF. Ischaemic heart disease (IHD) and cancer were the most common causes of CV and non-CV death regardless of EF category. The incidence rate of CV death due to IHD was highest in HFrEF while incidence rates of CV death due to pulmonary vascular disease, stroke, valvular heart disease and atrial fibrillation increased with increasing EF. The incidence rates of non-CV deaths due to cancer, respiratory disease, and infections increased with increasing EF., Conclusion: Cardiovascular death was more common than non-CV death across all EF categories although the risk of non-CV death within 5 years was higher with increasing EF. IHD and cancer were the most common causes of CV and non-CV deaths, respectively, regardless of EF category., (© 2024 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)