Heart Failure Population Research Articles

Recognition of the Large Ambulatory C2D Stage of Advanced Heart Failure-A Call to Action.

The advanced ambulatory heart failure (HF) population comprises patients who have progressed beyond the pillars of recommended stage C HF therapies but can still find meaningful life-years ahead. Although these patients are commonly encountered in practice, national databases selectively capture the small groups accepted for heart transplant listing or left ventricular assist devices. The epidemiology, trajectories, and therapies for other ambulatory patients with advanced HF are poorly understood. In December 2022, the National Heart, Lung and Blood Institute convened a team of experts to identify knowledge gaps and research priorities for the ambulatory population with limiting daily symptoms and transition toward refractory end-stage D HF, designated as stage C2D. This article summarizes the findings from that 3-day workshop. Workshop participants surveyed the initial challenges and knowledge gaps for (1) recognition of ambulatory C2D HF, (2) estimation of the magnitude of the affected population and identifiable subpopulations, and (3) physiologic phenotypes, such as low cardiac output, right HF, cardiorenal syndromes, congestive hepatopathy and frailty, which offer distinct targets for existing and emerging therapies. Social drivers of HF and patient preferences for quality/length of survival were highlighted as essential modifiers for personalization of therapies. Ten key points summarized workshop findings, with target cohorts for study proposed as a crucial next step. This workshop summary is intended as a call for action to address knowledge gaps and develop new strategies to improve outcomes in the large ambulatory population with C2D HF.

Smartwatches in the assessment of heart failure patients in epidemiology and pathophysiology studies: A scoping review.

A limited number of studies with smartwatches (SWs) investigated their potential in the field of heart failure (HF). The aim of this scoping review is to understand the extent of current literature on SWs in the HF population and the device's potential to improve disease management. The literature search was performed on PubMed and Embase in March 2024. Inclusion criteria included the use of commercialized SWs, HF diagnosis and peer-reviewed publications. Articles were excluded if the SW was not the study intervention or was part of a broader intervention programme. Reviews, case reports and study protocols were excluded. Of 1200 identified articles, 13 were included in the scoping review, encompassing 1171 patients with HF, and findings were presented in a descriptive summary table. Validity of several SW-collected physiological metrics was assessed against established technologies. Heart rate and step count measures were deemed moderately accurate in the HF population with Fitbit trackers (n=5 patients, r=0.54) and Garmin watches [n=15 patients (mean age: 65.5±12.6years), concordance correlation coefficient (CCC)=0.89 for Vivofit 1 and CCC=0.92 for Vivofit 3], respectively, while calorimetry was the least reliable measurement [n=19 patients (mean age: 65.1±6.6years), mean difference to indirect calorimeter: P=0.01 for Fitbit Charge 2, P=0.02 for Mio Slice]. Wrist-worn activity trackers were positively received by patients with HF [91.3% of adherence in research setting (n=70 patients, median age (IQR): 79years (76-82)), and 64% in real-world environment (n=14 patients)]and their health-care providers (six cardiologists out of six acknowledged the data's usefulness), although device ownership ranged from 10 to 50% among the HF population. Physical activity information collected from SWs was found to be valuable in assisting cardiologists with their New York Heart Association (NYHA) functional class assessment, which is known for its limited objectivity and reproducibility. Multiple studies found that SWs, especially Fitbit devices, successfully identified a pattern where the degree of exercise intolerance increased with higher NYHA classes. These findings suggested that activity trackers can objectively evaluate the severity of physical activity limitations. As the functional classification of patients influences treatment strategies, SWs could serve as a valuable tool to facilitate and optimize outpatient disease management. SWs could be used as a complement to standard monitoring in HF. With continuous technological advances, it will be valuable to follow the deployment of SWs and to investigate their contribution to increased patient safety and consequently to health care cost reductions.

Towards a Person-Centered After-Visit Summary to Facilitate Improved Heart Failure Care (HF-AVS): A Scoping Review and Call to Action.

Person-centered care (PCC) has been advanced as an optimal model of chronic heart failure management in multiple guidelines. However, fulfilling the ideal of this model requires overcoming healthcare fragmentation via effective provider-to-patient communication. One potential communication tool is the after-visit summary (AVS), a core feature of modern electronic health records (EHR); however, little is known regarding its quality from a PCC lens and whether an optimal AVS for the heart failure (HF) population has been created previously. We evaluate the history of AVS use in U.S. healthcare as well as map the extent and type of evidence on its quality, stakeholder perspectives, and attempts to perform PCC-related modifications across various healthcare settings as well as in acute-on-chronic or chronic HF specifically, evaluating if a HF-specific AVS (HF-AVS) has been reported. A search of the peer-reviewed literature was conducted via MEDLINE (Pubmed) and SCOPUS. Select gray literature was included if cited by peer-reviewed articles. Articles were included if they were: 1) written in English, 2) discussed an EHR-generated documented intended for provider-to-patient communication, & 3) were situated within the U.S. healthcare system. Two authors screened relevant articles, with disagreements resolved by consensus. If a resolution was not found the senior author broke ties. Data were extracted by one abstractor and checked by at least one additional abstractor. This scoping review found that the AVS became a part of the modern electronic health record via legislative action. Incentives for continued use are still in place. While AVS use is widespread its quality is poor, without the necessary readability for PCC models. Patient, provider, and care partner perspectives suggest the need to reduce medical jargon reduction and streamlining workflows; however, barriers exist the level of EHR vendors, preventing large PCC modifications. In contrast, small "embeddable" interventions appear more likely to be successful. No HF-AVS was identified; however, the modification of an existing patient-oriented discharge summary for heart failure (PODS-HF) was present, warranting exploration of embedding the document into EHRs. One potential HF specific "embeddable" intervention is free text prompting patient initiation and up titration of guideline-directed medical therapy and routing to HF nursing and pharmacist teams. If pursued, teams should secure funding, collaborate with EHR vendors, and trial these interventions with objective medication and/or exercise adherence. Limitations to this scoping review are present including the lack of a pre-registered protocol. Future work is needed to increase the quality of the AVS evidence base.

Speckle tracking parameters in the two genders in chronic heart failure: a multicentric italian study

Abstract Introduction the incidence of heart failure (HF) with reduced ejection fraction (EF, HFrEF) and with mildly reduced EF (HFmrEF) is globally lower worldwide and women are underrepresented in clinical trials. A deeper knowledge of possible gender differences in HF is needed to guarantee a better management. Purpose to evaluate left (LV) and right ventricular (RV) and left atrial (LA) longitudinal deformation by speckle tracking echocardiography (STE) in a population of patients with HF and ejection fraction (EF) <50%, to describe possible gender differences. Methods we retrospectively enrolled patients from 7 different Italian centers, referred to a high experience echocardiographic laboratory for stable chronic HF follow up. We excluded patients with preserved LV ejection fraction, recent admission for acute HF, previous cardiac surgery, and absent informed consent. All patients underwent complete standard and advanced echocardiography, including STE-derived LV, RV and LA strain. Kolmogorov-Smirnov test was used to verify normal distribution of variables. Continuous variables were compared using the unpaired t test for normally distributed variables and the nonparametric Mann-Whitney U test for non-normally distributed variables. Results a multicentric population of 644 patients (mean age 66.8±11.4, 237 female, 37%) was finally included in the study. The population had a globally reduced systolic function (mean LVEF 33.4±9.7%, mean LV global longitudinal strain (GLS) -9.7±3.5%) with abnormal RV longitudinal deformation (mean free wall RVLS -17.6±6.1%), increased pulmonary pressures (sPAP 35.1±12 mmHg) and diastolic disfunction (LA strain (PALS) was 16.3±8%, mean E/e’ ratio 12.2±3.6). Analyzing the female population with HF (see Table 1), women had lower LV and RV mass and diameters. The LA was smaller, but they had similar diastolic indices compared to man. Interestingly, deformation analysis revealed comparable LV, LA, and RV longitudinal strain in the two genders. Conclusion female HF population seems to have similar cardiac longitudinal dysfunction compared to men. It could be then credible to expect similar therapeutic response to HF drugs in the two genders. Further studies are needed to evaluate different echocardiographic prognostic parameters across gender in HFrEF and HFmrEF.

Relaxin mimetic in pulmonary hypertension associated with left heart disease: Design and rationale of Re-PHIRE.

Despite receiving guideline-directed medical heart failure (HF) therapy, patients with pulmonary hypertension associated with left heart disease (PH-LHD) experience higher mortality and hospitalization rates than the general HF population. AZD3427 is a functionally selective, long-acting mimetic of relaxin, a hormone that has the potential to induce vasodilation and prevent fibrosis. In a phase 1b study conducted in patients with HF, AZD3427 demonstrated a favourable safety and pharmacokinetic profile. To address the unmet medical need in patients with PH-LHD in the context of HF, AZD3427 is currently under development as a potential treatment option. The Re-PHIRE study is a phase 2b, randomized, double-blind, placebo-controlled, multicentre, dose-ranging study to evaluate the effect of AZD3427 on a broad range of PH-LHD phenotypes. In total, 220 patients will be randomized to four treatment groups to receive a subcutaneous injection of AZD3427 or placebo every 2weeks for 24weeks. The primary endpoint of the study is the change in pulmonary vascular resistance in patients treated with AZD3427 versus placebo after 24weeks of treatment. Key secondary endpoints include changes in mean pulmonary arterial pressure, pulmonary artery wedge pressure, systemic vascular resistance, 6-min walking distance, N-terminal pro B-type natriuretic peptide levels, echocardiographic parameters, and health-related quality of life (assessed by the Kansas City Cardiomyopathy Questionnaire). Re-PHIRE is the first study of a relaxin mimetic in patients with PH-LHD. The insights gained from the Re-PHIRE study are expected to inform the further development of AZD3427 in the PH-LHD population, including identifying the most suitable pulmonary hypertension and HF phenotypes for treatment.

Association of Immune Nutrition Indices with the Risk of All-Cause Mortality and Cardiovascular Mortality in Patients with Heart Failure in the NHANES (1999-2018).

Heart failure (HF) remains a global challenge with disappointing long-term outcomes. Malnutrition is prevalent in patients with HF and disrupts the equilibrium of immune and inflammatory responses, resulting in further deterioration of the HF. Novel indicators emerge as immune nutrition indices, including the prognostic nutritional index (PNI), neutrophil-to-lymphocyte ratio (NLR), Controlling Nutritional Status (CONUT) score, and cholesterol-modified prognostic nutritional index (CPNI). This study examines the correlation between immune nutrition indices and all-cause and cardiovascular mortality in patients with HF. The data source for this study was the National Health and Nutrition Examination Survey (NHANES). A total of 1232 participants with HF were included. Weighted Cox proportional hazards models were employed to assess the independent association of different immune nutrition indices with mortality risk, alongside subgroup analyses and Kaplan-Meier survival curves. Restricted cubic spline analysis was utilized to clarify the detailed association between immune nutrition indices and hazard ratio (HR). A time-dependent receiver operating characteristic curve analysis was conducted to assess the predictive ability. After full adjustments, PNI is independently related to all-cause mortality (HR = 0.94, 95% CI: 0.92-0.97) and cardiovascular mortality (HR = 0.94, 95% CI: 0.90-0.99). CPNI, CONUT, and NLR also showed an independent association with the prognosis of HF. Time-dependent receiver operating characteristic curve analysis indicated that PNI exhibited the highest predictive power for mortality among the CPNI, CONUT, and NLR indexes. Our study revealed that immune nutrition indicators, including CPNI, could predict all-cause mortality and cardiovascular mortality in the HF population. Compared with other indicators, PNI is the most effective predictor.

Evaluation of Subclinical Systolic Dysfunction in Patients with Heart Failure with Preserved Ejection Fraction, Using 2D Speckle Tracking Echocardiography

Background: Originally thought to be purely due to LV diastolic dysfunction, studies according to western countries have suggested that heart failure with preserved ejection fraction (HFpEF) is more complex. In patients with HFpEF, global LV systolic function is commonly considered normal as the global ejection fraction (EF) is normal. However, the EF reflects only the global cardiac contractile function and does not take the subclinical systolic function into consideration. Therefore, more attention should be paid on this subset of heart failure population in which the frequency of subclinical systolic dysfunction has not been clearly identified. Objective: The principal objective of this study was to assess the global longitudinal systolic function of the LV in Bangladeshi patients with HFpEF using from 2D speckle tracking echocardiography. Methods: This study was conducted from May 2018 to April 2019 in department of cardiology, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh. A total of 31 patients with HFpEF were enrolled in the study. Detailed history was taken including NYHA functional class, relevant physical examinations and investigations were done. 2D echocardiography, color Doppler, tissue Doppler and 2D speckle tracking echocardiography were done. GLS was obtained in a total of 31 patients with HFpEF diagnosed according to the 2016 European Society of Cardiology (ESC) guidelines for the diagnosis and treatment of acute and chronic heart failure. Result: All patients with HFpEF had preserved LV ejection fraction (LVEF>50%) and evidence of diastolic dysfunction. Majority of study subjects had reduced GLS when -18% was used as the lower limit of normal as per vendor specific recommendations. Conclusion: Subclinical systolic dysfunction was frequent in the majority of HFpEF patients. Further large-scale studies are recommended to confirm the findings of this study. University Heart Journal 2024; 20(1): 3-9

Center- vs Home-Based Cardiac Rehabilitation in Patients With HeartFailure: EXIT-HF Randomized Controlled Trial.

Despite being an evidence-based intervention, the implementation of cardiac rehabilitation (CR) is often unsatisfactory, especially among patients with heart failure (HF). Home-based CR can serve as an alternative to improve accessibility for patients unable to participate in center-based programs. The study sought to compare the clinical impact of center- vs home-based CR in HF patients. Single-center, parallel group, noninferiority trial, enrolling HF patients irrespective of ejection fraction. Patients were randomly allocated in a 1:1 ratio, then adjusted to a 1 center/2 home ratio during the COVID-19 pandemic, then adjusted to 12weeks of a standard center-based (24 supervised exercise sessions) or home-based CR (4 supervised sessions plus 20 sessions at home, asynchronously monitored by telephone using wearable smartwatch data) program. The primary outcome was change in peak oxygen uptake (Vo2peak) at 12weeks. Of the 120 patients (age 62 ± 11 years, 66% men, mean left ventricular ejection fraction 36 ± 11%) who were randomized to center-based (n = 45) or home-based (n=75) CR, 95 (79%) had complete Vo2peak data at the 12-week assessment: 34 (76%) in the center-based group and 61 (81%) in the home-based group. No significant between-group differences were found in Vo2peak change from baseline to week 12 (0.8mL/kg/min [95%CI: 1.8 to-0.16mL/kg/min]; P = 0.10). Additionally, no between-group differences were found for changes in the prespecified secondary outcomes: 6-minute walking distance, Minnesota Living with HeartFailure Questionnaire scores, disease-related biomarkers, and physical fitness. Exercise adherence to the CR program was similar between groups (home-based 84% vs center-based 81%). In a contemporary well-treated HF population, home-based CR was noninferior to the center-based program, supporting the home-based approach as an effective and feasible alternative to the traditional center-based programs. (EXercise InTervention in HeartFailure [EXIT-HF]; NCT04334603).

Investigation of left ventricular ejection fraction in a Swiss heart failure population: Insights into mortality and sex differences.

Understanding heart failure (HF) characteristics is essential to improve patient outcomes. Categorizing HF beyond left ventricular ejection fraction (LVEF) is challenging due to heterogeneous clinical presentation and aetiologies. Despite global studies on HF, the role of LVEF on mortality remains controversial. We explored the association of LVEF with mortality, considering sex differences and comorbidities in a cohort from the largest tertiary cardiovascular centre in Switzerland. HF patients admitted to the University Hospital of Bern from January 2015 to December 2019 were evaluated. LVEF was used to classify patients into HF with preserved ejection fraction (HFpEF), HF with mid-range ejection fraction (HFmrEF) and HF with reduced preserved ejection fraction (HFrEF) categories. Cox proportional hazard models and time-stratified analyses adjusted for potential confounders were employed. A total of 5824 HF patients were included, and 2912 died over a median follow-up time of 3.39years. Mortality rates across LVEF categories showed no significant differences, while overall, women showed significantly higher mortality; 30day mortality was lower in the HFpEF category [hazard ratio (HR) 0.67, 95% confidence interval (CI): 0.52-0.88, P=0.003], with persistent effects upon stratification in males (HR 0.59, 95% CI: 0.42-0.81, P<0.001) and non-diabetics (HR 0.62, 95% CI: 0.44-0.87, P=0.005). An isolated reduction in HFpEF mortality was observed in females after 1year (HR 0.72, 95% CI: 0.53-0.98, P=0.035). The prognostic role of LVEF on all-cause mortality remains unclear, while differences in mortality rate distribution between women and men mirror established HF pathophysiological sex differences. Future HF studies should focus on HF aetiology and include measures beyond LVEF for comprehensive characterization.

Comparison of Urine Output Response of Intravenous Bumetanide and Furosemide in Acute Decompensated Heart Failure: an observational analysis.

Loop diuretics are a fundamental cornerstone in management of hypervolemia encountered in acute decompensated heart failure. There is variation in literature describing relative potency of loop diuretic agents, and very limited available data specific to the heart failure population. In this retrospective cohort study, we aimed to compare the urine output response between intravenous furosemide and bumetanide in patients with acute decompensated heart failure. Patients were eligible for inclusion if they were admitted between July 1, 2021 and June 30, 2022, with acute decompensated heart failure and received intravenous bumetanide or furosemide within 48 hours of admission. Propensity matching was utilized to determine comparison groups. The primary outcome was total urine output for 24 hours following initiation of the diuretic regimen. A total of 120 patients (60 in each group) were matched after exclusion criteria were applied. The total urine output was similar between groups. The bumetanide group did demonstrate a greater urine output: furosemide equivalent response (52 ± 46 mL/mg versus 33 ± 25 mL/mg; p=0.007). Based on our analysis, similar urine output may be achieved with either intravenous bumetanide or furosemide in acute decompensated heart failure; however a higher dose of furosemide may be required than what has been previously established as an equivalent dose to bumetanide to achieve a similar diuretic effect. These results should warrant further investigation to better establish dose-response relationships with loop diuretics in the acute decompensate heart failure.

Review of Current Normothermic Regional Perfusion Practice in Pediatric Cardiac Donation.

Cardiac allotransplantation is the optimal treatment for end-stage heart failure. However, organ supply remains the principal issue impacting patients. Pediatric patients present unique challenges resulting in long wait-list times and increased mortality. Donation after circulatory death with normothermic regional perfusion represents a method to increase the number of available organs in this population. Multi-institutional expert consultation was sought to outline extant technical, ethical, and logistical issues with regard to normothermic regional perfusion cardiac donation techniques. Specific advantages in the pediatric population are highlighted, as well as technical considerations resulting in successful organ procurement. Utilization of donation after circulatory death organs following normothermic regional perfusion in the United States is increasing and offers advantages to the pediatric heart failure population. Ethical reservations both nationally and abroad persist, namely pertaining to cerebral blood flow. This has led to variation in perception and utilization of normothermic regional perfusion, contributing to a discrepancy between donor and recipient locations. Procurement techniques and variations are described, with introduction into program planning and protocol development. Training in technical aspects of the procedure is paramount for both the surgeon and support staff to construct a successful program, along with transparent protocols to mitigate ethical concerns. Normothermic regional perfusion is relevant following donation after cardiac death in the pediatric population. Ethical and technical challenges remain in concert with substantial domestic and international variation. Standardization of technique may serve to increase future use and increase the number of available hearts for transplant, reducing pediatric mortality.

Implementing a Telemedicine-led Heart Failure Medication Regimen Optimization Clinic in Medically Underserved Heart Failure Populations.

Suboptimal guideline-directed medical therapy (GDMT) management for heart failure (HF) are critical issues in rural communities. Most patients with HF in rural communities are treated in primary care settings. Multidisciplinary telemedicine-led HF medication optimization clinics were implemented to improve access to the specialty care and address health disparities in HF care in rural Appalachian areas. The project aimed to evaluate the effect of a multidisciplinary telemedicine HF medication optimization clinic on the use of GDMT in cardiology and primary care services. This pilot study was a multi-center prospective cohort study over a 6-month follow-up periods. Patients aged >18 years with HFrEF or HFmrEF were included. Telemedicine visits were conducted every 2 to 4 weeks. The primary outcome was the use of all four GDMT classes. The use of all four GDMT was numerically higher in HF cardiology service (n=70) compared to the general cardiology cohort (n=11) at baseline (46 vs. 9%), at 1 month (55 vs. 18%), at 3 months (58 vs. 18%), and 6 months (52 vs. 18%). The individual use of angiotensin receptor neprilysin inhibitor (ARNI), mineralocorticoid receptor antagonist (MRA) or sodium-glucose cotransporter-2 inhibitor (SGLT 2 I) was also numerically higher in HF cardiology service over 6 months. In the primary care service (n=25), the use of all four GDMT agents was not significantly changed over 6 months. ARNI and beta-blocker use was numerically increased from the baseline to follow-up periods. MRA use was numerically decreased from baseline to follow-up periods. SGLT 2 I use was not significantly changed. The multidisciplinary telemedicine approach was effective in the HF service group for GDMT optimization. However, further academic detailing for primary care and general cardiology services is needed, focusing on the initiation and persistence of MRA and SGLT2I, and dose titration of GDMT agents.

EGFR slope as predictor of mortality in heart failure patients.

Heart failure (HF) leads to an imbalance between heart and kidney function, resulting in poor outcomes. However, the prognostic significance of the estimated glomerular filtration rate (eGFR) trajectory in HF patients remains unclear. We analysed electronic health records (EHRs) of real-world HF patients, assessing eGFR trajectories and their impact on mortality. Retrospective clinical data of HF patients were processed using natural language processing. Chronic kidney disease (CKD) was evaluated, and eGFR trajectories were analysed using linear mixed-effects models. Cox proportional hazard models were used to evaluate the relationship between baseline variables and mortality, while joint modelling combined eGFR trends and mortality. The dataset comprised 1986 patients, with a mean age of 74.8years (SD±11.7) and 58% male. At the time of HF diagnosis, 58% of patients were diagnosed with CKD, and 39% presented with heart failure with preserved ejection fraction (HFpEF). The median follow-up duration was 3.16years, during which 399 patients (20%) died. Patients with CKD were significantly older and exhibited a higher prevalence of myocardial infarction (P=0.048), coronary revascularization (P=0.004), stroke (P<0.001), atrial fibrillation (P<0.001) and type 2 diabetes (P<0.001). Mortality rates at 1 and 2years were nearly twice as high in CKD patients compared with those without (P<0.001). Notably, CKD was significantly less prevalent among survivors (55% vs. 71%, P<0.001). Key predictors of mortality included older age, beta-blocker use, prior stroke, lower serum haemoglobin levels, and elevated potassium and NT-proBNP levels. Each 10mL/min/1.73m2 decrease in eGFR was associated with a 1.22 (95% CI: 1.10-1.35, P<0.001) increase in mortality hazard. Additionally, a 1-year decline of 10mL/min/1.73m2 in eGFR resulted in a mortality hazard of 1.97 (95% CI: 1.45-2.69, P<0.001). CKD is prevalent in a real-world HF population and is an independent predictor of mortality. The current eGFR value and the eGFR slope from the previous year have the potential to be used for assessing individual mortality risk in the clinical follow-up of HF patients.

The effects of Dapagliflozin in a real-world population of HFrEF patients with different hemodynamic profiles: worse is better

BackgroundSodium-Glucose Cotransporter-2 inhibitors (SGLT2i) represent a deep revolution of the therapeutic approach to heart failure (HF), preventing its insurgence but also improving the management of the disease and slowing its natural progression. To date, few studies have explored the effectiveness of SGLT2i and, in particular, Dapagliflozin in a real-world population. Therefore, in this observational prospective study, we evaluated Dapagliflozin's effectiveness in a real-world HF population categorized in the different hemodynamic profiles.MethodsFrom January 2022 to June 2023, we enrolled 240 patients with chronic HF and reduced ejection fraction (HFrEF) on optimal medical therapy, according to 2021 ESC guidelines, that added treatment with Dapagliflozin from the HF Clinics of 6 Italian University Hospitals. Clinical, biochemical, and echocardiographic parameters were collected before and after 6 months of Dapagliflozin introduction. Moreover, the HFrEF population was classified according to hemodynamic profiles (A: SV ≥ 35 ml/m2; E/e′ < 15; B: SV ≥ 35 ml/m2; E/e′ ≥ 15; C: SV < 35 ml/m2; E/e′ < 15; D: SV < 35 ml/m2; E/e′ ≥ 15). Then, we compared the Dapagliflozin population with two retrospective HF cohorts, hereinafter referred to as Guide Line 2012 (GL 2012) group and Guide Line 2016 (GL 2016) group, in accordance with the HF ESC guidelines in force at the time of patients enrolment. Precisely, we evaluated the changes to baseline in clinical, functional, biochemical, and echocardiographic parameters and compared them to the GL 2012 and GL 2016 groups.ResultsDapagliflozin population (67.18 ± 11.11 years) showed a significant improvement in the echocardiographic and functional parameters (left ventricular ejection fraction [LVEF], LV end-diastolic volume [LVEDV], LVEDV index, stroke volume index [SVi], left atrium volume index [LAVi], filling pressure [E/e′ ratio], tricuspid annular plane systolic excursion [TAPSE], tricuspid annular S′ velocity [RVs’], fractional area change [FAC], inferior vena cava [IVC diameter], pulmonary artery systolic pressure [sPAP], NYHA class, and quality of life) compared to baseline. In particular, TAPSE and right ventricle diameter (RVD1) ameliorate in congestive profiles (B and D); accordingly, the furosemide dose significantly decreased in these profiles. Comparing the three populations, the analysis of echocardiographic parameters (baseline vs follow-up) highlighted a significant decrease of sPAP in the Dapagliflozin population (p < 0.05), while no changes were recorded in the GL 2012 and GL 2016 population. Moreover, at the baseline evaluation, the GL 2012 and 2016 groups needed a higher significant dose of furosemide compared to Dapagliflozin group. Finally, Dapagliflozin patients had significantly fewer rehospitalizations (1.25%) compared with the other two groups (GL 2012 18.89%, p 0.0097; GL 2016 15.32%, p 0.0497).ConclusionsWe demonstrate that Dapagliflozin is rapidly effective in an HFrEF real-world population; furthermore, the more significant effect is recorded in HFrEF patients with a congestive profile (B and D), supporting the introduction of Dapagliflozin in patients with a congestive profile and a worse prognosis. In conclusion, our data suggest evaluating the patient's hemodynamic state beyond LVEF in HFrEF.

Abstract 4120496: Cannabis Use Among Heart Failure Hospitalizations and Cardiovascular Outcomes. A Five-Year Retrospective Study

Introduction: The use of cannabis is on the rise. A few retrospective studies have demonstrated an association between cannabis use and ischemic heart disease and stroke. However, its implications in the already established heart failure (HF) population has not been well studied. We aimed to address this gap. Methods: We employed the National Inpatient Sample database (2016-2020) and used ICD-10 codes to identify all patients ≥18 years old with a history of HF. Then, we divided them into two groups: those with and without a history of cannabis use. A greedy nearest-neighbor 1:1 propensity score matching (PSM) followed by multivariable logistic regression analysis was used to account for baseline differences (including cigarette smoking) and to predict the outcomes. The outcomes were ST-segment elevation myocardial infarction (STEMI), non-STEMI (NSTEMI), uncontrolled hypertension (HTN), arrhythmias, acute kidney injury (AKI), and stroke. Results: Of the 4,283,620 HF hospitalizations, 1.6% (67,795) used cannabis, and 72% (48,825) were male. Compared to the non-cannabis group, the group with cannabis use was younger, with a mean age of 53 vs 68 years, p&lt;0.0001. After PSM, 56,233 with a history of cannabis use were matched to 56,233 hospitalizations without cannabis use history. The population with cannabis use had a higher association with uncontrolled HTN 1.5 (1.4-1.6), NSTEMI 1.3 (1.23-1.36), STEMI 1.15 (1.05-1.25), stroke 1.14 (1.05-1.23), and AKI 1.05 (1.02-1.1), (p&lt;0.0001, for each). Arrhythmias 0.96 (0.94-1.01, p=0.1) did not differ between both groups. Conclusion: Among the hospitalized HF population, those with a history of cannabis use had a higher association with uncontrolled HTN, STEMI, NSTEMI, AKI, and stroke. They were also younger than their non-cannabis use counterparts. More research is needed to determine the significance of these findings.

Abstract 4147647: Effects on Cognition, Sleep, Quality of life and Exercise Capacity of a 12-week Tele-yoga Intervention in Persons with Heart Failure - Results from 3 and 6 Months Follow-up

Background and Objectives: Yoga may be a promising form of mind-body rehabilitation for patients with long term illness. Digitally delivered yoga increases access to participation but has not previously been evaluated in the heart failure population. The aim of this study was to examine the effects of tele-yoga on cognition, sleep, health-related quality of life and exercise capacity in persons with heart failure. Methods: The Tele-yoga study (ClinicalTrials.gov, ID: NCT 03703609) was a parallel two-arm randomised controlled trial (RCT) with 1:1 distribution to an intervention and control group. Study participants were randomised to tele-yoga including live-streamed group-yoga for 60 minutes twice weekly during 12 weeks and yoga individually for 10 minutes/day using an app, or to a control group receiving individual exercise advice. Cognition (Montreal Cognitive Assessment: MoCA), sleep (minimal insomnia symptom scale; MISS), health-related quality of life (EQ-5D VAS) and sub-maximal exercise capacity (6 minute walk test; 6MWT) were assessed at baseline, after 3 and 6 months. Linear mixed model with random intercept for patients as the random effect and group-time interaction along with age was taken as the fixed effects to analyse outcomes. Results: A total of 311 participants were included (tele-yoga n=156 and active controls n=155), mean age 66 years, 70% men. Adherence to the group yoga was very good. The linear mixed models showed a significant change in cognition, health-related quality of life and exercise capacity favouring the tele-yoga group. No significant differences between the groups were seen regarding sleep. When analysing the fixed effects of all outcomes, age, group assignment and time-points interaction had significant effects on EQ-5D VAS score, 6MWT distance and MoCA scores. For EQ-5D VAS the tele-yoga group performed significantly better than the control group at 3 months, but not at 6 months. For the 6MWT distance, the tele-yoga group performed better than the control group at 3 months, but not at 6 months. The tele-yoga group had significantly higher MoCA scores than the control group at both 3 and 6 months. Conclusion: This adequately powered RCT showed that digitally delivered mind-body training in the format of group and individual yoga during 12 weeks lead to an improvement in cognition, quality of life and exercise capacity at the end of the intervention. The effect was sustained for cognition also after 6 months.

Abstract 4127562: Age, Adiposity-Related Anthropometrics, and Clinical Outcomes in Heart Failure with Mildly Reduced or Preserved Ejection Fraction: A Participant-Level Pooled Analysis of Randomized Trials

Background: Age has been shown to modify the population-level association between body mass index (BMI) and mortality. However, whether age modifies the association between adiposity-related anthropometrics and adverse outcomes in heart failure (HF) populations has not been systematically explored. Methods: In this participant-level pooled analysis of five international, multicenter, randomized-controlled trials enrolling adults with HF and either mildly reduced or preserved ejection fraction (HFmrEF/HFpEF), the association between age and adiposity-related anthropometrics (BMI, waist circumference [WC], and waist-to-height ratio [WHtR]) and the primary composite outcome of time-to-first HF hospitalization or cardiovascular (CV) death was evaluated using multivariable adjusted Cox proportional hazards models (stratified by treatment and trial) and restricted cubic splines. Results: Among 21,606 participants in the analysis (mean age, 71±9 years; 49% female; 83% White; mean BMI, 30±6 kg/m 2 ), 5,350 (25%) were aged &lt;65 years, 8,273 (38%) were aged 65-74 years, and 7,983 (37%) were aged ≥75 years at baseline. Older individuals were more likely to be female, have lower BMI and WC, and higher left ventricular ejection fraction. Overall, BMI, WC, and WHtR were steeply and non-linearly associated with the primary outcome ( Figure ). Age, as either a categorical or continuous variable, significantly modified the covariate-adjusted association between all anthropometrics and the primary composite outcome ( P ≤0.001 for all) ( Figure ). A J-shaped relationship, characterized by higher incidence of the primary outcome with lower anthropometric values, was observed only for BMI and was substantially attenuated among younger adults. Irrespective of the anthropometric used, increasing adiposity was most steeply associated with primary events among adults aged &lt;65 years. Conclusions: In this pooled analysis of HFmrEF/HFpEF trials, age was a powerful modifier of the relationship between excess adiposity and HF hospitalization or CV death. An “obesity-survival paradox” – observed only for BMI – was not apparent in younger participants, who exhibited the steepest increase in the rate of clinical events with higher adiposity.

Abstract 4135905: The Impact of Emergent Atrial Fibrillation in Patients With Newly Diagnosed Heart Failure and Differences in Risk Among Preserved vs. Reduced Ejection Fraction

Background: Atrial fibrillation (AF) and heart failure (HF) are associated with an increased risk of adverse events, with their diagnoses often coexisting. The impact of AF in HF needs additional study, with further delineation among HF type. Therefore, this study sought to determine the degree of AF burden among newly diagnosed HF patients and whether differences in risk exist between heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF) patients. Methods: Patients with new-onset HF between 2000-2019 were studied. To be included, patients had to have 1-year of follow-up, an ejection fraction (EF) measurement within 30 days of HF diagnosis, and no history of cancer. EF was used to define HFrEF (EF &lt;40%) and HFpEF (EF &gt; 40%). Multivariable Cox hazard regression was used to evaluate the risk of death and HF hospitalization at 1- and 3-years. Results: A total of 21,925 patients were studied with HFrEF (n=7931 [36.2%]) and HFpEF (n=13,994 [63.8%]). HFpEF patients were older (74 vs. 65 years) and more often female (53.7% vs. 33.1%). Prevalent AF was 40.5% (n=8879), being more common in HFpEF compared to HFrEF (65.2% vs. 34.8%). Among AF patients, HFpEF patients were also older (76 vs. 72 years) and more often female (52.7% vs. 30.8%) compared to HFrEF. The presence of AF was associated with an increased risk of HFpEF (OR=1.11, p=0.001). Prevalent AF was associated with an increased risk of death and follow-up HF hospitalization (Table). Death at 1-year and 3-years were similar between the HF groups (Table). However, the risk of HF hospitalization was greater among HFrEF patients (Table). Similar associations persisted when AF patients were propensity matched (Table). Conclusions: Among a newly diagnosed HF population, AF was common (40%) and was associated with an increased risk of HFpEF, death, and HF hospitalization. These results provide a rationale for aggressive management of HF and AF patients and the need for a randomized clinical trial to determine optimal therapy by ablation and 4-pillar HF therapy.

Symptoms Burden as a Clinical Outcomes Assessment in HeartFailure Patients With Atrial Fibrillation.

Safe and effective pharmacologic therapy for atrial fibrillation (AF) in heart failure (HF) is an unmet need. In AF clinical trials, the standard primary endpoint of time to first symptomatic AF event (TTFSE) has several disadvantages, which could theoretically be overcome by measurement of AF-specific symptoms burden during an entire follow-up period. The authors sought to develop and validate a method of measuring symptom burden of AF in a HF population. The authors constructed a patient-reported outcome instrument (Atrial Fibrillation Symptoms Questionnaire [AFSQ]) to function in the setting of AF/HF, and used it to measure symptoms throughout long-term follow-up. The AFSQ queries the presence of 10 new or worsening symptoms, equally divided between those associated with AF or HF. In a 267 patient AF/HF trial comparing 2 AF prevention treatments, the AFSQ was linked to electrocardiography documented AF to form a 2-component clinical outcome assessment (SxBAF) that was subjected to psychometric testing, anchor validation, and endpoint efficiency comparison to TTFSE. SxBAF exhibited greater efficiency than time to first symptomatic event for treatment difference detection, resulting in smaller projected clinical trial sample sizes. SxBAF correlated well with device-detected AF burden (Spearman's ρ=0.74; P< 0.0001), while permitting gradation in symptom severity. SxBAF also identified treatment group differences in cardiovascular serious adverse events and AF interventions and in recent-onset AF provided specificity for AF- or worsening HF-associated symptoms (P< 0.001 for each). Measurement of symptoms burden throughout clinical trial follow-up is feasible in AF/HF and should be useful for evaluating patient-centered outcomes in AF prevention trials. (Genetically Targeted Therapy for the Prevention of Symptomatic Atrial Fibrillation in Patients With HeartFailure [GENETIC-AF]; NCT01970501).

Impact of Sacubitril/Valsartan in Improving Home Time for Patients With Heart Failure.

Home time, defined as time spent by the patient alive and out of any healthcare institution, is an important patient-centric outcome for patients with cardiovascular disease. Home time is recognized as a crucial measure of recovery post cardiovascular events but has not been extensively studied in heart failure (HF) patients, especially in India. HF in India is rapidly growing at an epidemic scale and hence the focus on improving home time in HF patients highlights the need for precise, patient-centered care strategies. Current literature lacks detailed descriptions of hospital-level patterns and predictors of home time in contemporary HF populations, which hinders tailored approaches to optimize outcomes like functional status and health-related quality of life along with reduced hospitalization and mortality risks. Literature is abundant with clinical evidence on the benefits of guideline-directed medical therapy (GDMT), especially angiotensin receptor neprilysin inhibitor (ARNI) therapy, in HF management. All major guidelines highly recommend its initiation for reducing morbidity and mortality in patients with chronic symptomatic HF with reduced ejection fraction. Studies indicate that sacubitril/valsartan, the first in class of ARNI, improves the quality of lifeand functional outcomes, along with reduced HF-related hospitalizations and cardiovascular deaths. Its unique mechanism of action, combining neprilysin inhibition and angiotensin receptor blockade, targets multiple pathways of HF pathophysiology, leading to improved cardiac function and remodeling. These benefits are pivotal in supporting patients' ability to maintain an active lifestyle outside of healthcare settings. Despite its demonstrated benefits, sacubitril/valsartan is underutilized. Integrating sacubitril/valsartan more optimally into clinical practice could significantly alleviate the overall burden of HF by addressing key determinants of home time and improving patient outcomes post discharge.