HFrEF Patients Research Articles

Abstract 18190: Role of Specialised Heart Failure Unit in Optimisation of Guideline-Directed Medical Therapy With Focus on Renal Function - Real World Data

Introduction: Guideline-directed medical therapy (GDMT) has proven to significantly reduce morbidity and mortality in Heart Failure. We highlighted the differences in renal function among HF patients managed on GDMT, comparing those within a dedicated HF unit (HFU) to those under General Medical (GM) and Geriatrics (GER). Aim: The purpose of this single-centre cohort study is to highlight differences in renal function outcome between these groups. Methods: Our database consists of 540 patients with AHF admitted to HFU or GM/GER from 01/08/2021 to 31/07/2022. We divided this group as follows: Group A : 267 patients from GM/GER. Group B : 273 patients in HFU.Groups were classified by ejection fraction(HFrEF/HFmrEF/HFpEF). We analyzed eGFR, K+ and Creatinine(Cr) on admission(adm) and discharge(dc). Results: Group A(GM/GER) : HFrEF patients had average eGFR of 45.70(mL/min) on adm and 43.58 on dc. HFmrEF subgroups had eGFR of 48.60 on adm and 46.54 on dc. HFpEF subgroups had eGFR of 50.16 on adm and 47.75 on dc. Group B(HFU): Patients with HFrEF had eGFR of 53.50 on adm and 50.74 on dc. HFmrEF subgroup had adm eGFR of 49.48 and 47.01 on dc. HFpEF subgroups had eGFR of 45.95 on adm and 41.72 on dc. Group A and B comparison : We have previously demonstrated (Fig.1) that among patients with AHF managed in HFU, there is better optimisation of GDMT. Within the HFrEF cohort, eGFR decreased -2.76 in Group B, with reduction of -2.12 in Group A. Group B HFmrEF showed reduced eGFR of -2.47; Group A decreased -2.06. In HFpEF, eGFR reduced -4.23 in Group B. In Group A, eGFR decreased -2.41. An inpatient mortality of 15.73% was calculated in Group A, contrasting significantly with 6.23% among the HFU cohort. Conclusion: This study highlights differences in renal function outcome between these two groups. It demonstrates that despite optimisation and initiation of GDMT in Group B - which may lead to concern for its impact on renal function - eGFR, Cr and K+ levels were not markedly different between both cohorts.

Abstract 14356: Higher Burdon of Premature Ventricular Complexes is Not Uncommon in Stable Well Treated Heart Failure Patients and Relate to Poorer Outcomes

Introduction: While premature ventricular contractions (PVCs) are generally considered benign, recent evidence suggests that even the contractions preceding PVCs are inefficient so that even a moderate burden of PVCs may be associated with loss of contractile efficiency and increased risk of events. It is however unclear what proportion of stable heart failure (HF) patients have a moderate to high burden of PVCs, despite being well-treated. Aim: The aim of this study was to assess the proportion of HF patients that have more than 5% PVCs and whether this higher number is related to worse outcomes. Methods: We retrospectively analyzed electronic medical records from 676 adult patients with either an ejection fraction < 40% or NTproBNP more than 600 pg/ml at the Amsterdam UMC (AMC) who received Holter monitoring between 2014 and 2022. In a second independent cohort from a heart failure registry at Henry Ford Hospital (HFH) in Detroit, Michigan, we retrospectively reviewed all participants with ejection fraction < 40% that had a Holter monitor at any point (n=180). Results: The median baseline age of the Amsterdam UMC patients was 62 and 40% were female. The HFH cohort had a median age of 64 years and 50% were female. Results are summarized in the table. During the follow-up period, significantly more patients died in the group with more than 5% PVCs (p < 0.05 in the Amsterdam UMC cohort). Conclusions: We show in two independent cohorts that around 8-10% of HF patients have a significant burden of PVCs (i.e. >5% of all heartbeats), despite adequate use of beta-blocker therapy. This proportion of PVCs is associated with an increased risk of death over one year. This suggests that in HFrEF patients, PVCs burden more than 5% of heartbeats may not be as harmless as often thought.

Abstract 18454: Temporal Trends in Assessment and Management of Iron Status in Patients With Heart Failure: A Multi-Institutional Study

Background: Over the last decade there has been extensive investigation of iron deficiency in heart failure (HF). HFrEF patients are often refractory to oral iron supplementation whereas intravenous (IV) iron repletion has been shown to improve functional capacity, prompting a Class II guideline recommendation to assess iron stores and replete iron intravenously. The purpose of this study is to understand temporal patterns in assessment of iron status as well as utilization of oral and IV iron preparations in patients with HF. Methods: The Mass General Brigham (MGB) Research Patient Data Registry (RPDR) was used to conduct a retrospective analysis of patients with both HFrEF and HFpEF across 3 1-year intervals in 2012, 2017, and 2022. Circulating levels of iron, ferritin, and transferrin saturation (TSAT) were assessed. Patients were further classified according to the HF guideline-based definition of iron deficiency (ferritin <100 ng/mL or 100-299 ng/mL with a TSAT < 20%). Iron deficient (ID) HF patients were assessed for use and frequency of IV iron or oral iron for repletion. Results: Electronic health records within the MGB Healthcare System identified 23,687 total HF patients in 2012, 25,271 in 2017, and 36,059 in 2022. Among these patients, the percentage with iron studies measured within the calendar year were 48%, 62%, and 90% respectively. Of those with HF 5,557 (23%), 8,460 (33%), and 19,955 (55%) met guideline-based diagnostic criteria for iron deficiency. Oral iron supplements were used in 68%, 44%, and 19% of all ID HF patients. IV iron was given to only 4%, 11%, and 14% of ID patients ( Figure ). Conclusion: The temporal trends of iron assessment and repletion demonstrate a significant increase in assessment of iron stores by health care providers but persistent utilization of oral formulations in excess of IV formulations to treat ID. These data suggest a significant gap in implementation of a therapy associated with functional improvement in HF.

Abstract 12519: Biomarker Characterisation of Heart Failure Subtypes: A Population-Based Bioresource Linked Study

Background: Deep learning (DL)-based interpretation of echocardiographic images can help create pragmatic cohort studies to validate novel biomarkers. In this study, we have characterised biomarkers implicated in heart failure (HF) pathophysiology across the ejection fraction (EF) range in a DL-supported pragmatic cohort study. Methods: We used electronic health record data from Tayside, representing 20% of the Scottish population, between 1993 and 2021. Utilising record linkage to DL automated reading of echocardiographic DICOM images, we identified patients with HFrEF or HFpEF and patients without HF. We then linked identified patients to available plasma samples from the Go-SHARE BioBank. We analysed multi-panel biomarkers, such as NT-proBNP, high-sensitivity cardiac troponin-T (hs-cTnT), growth differentiation factor-15 (GDF-15), insulin-like growth factor-binding protein-7 (IGFBP-7), bone morphogenetic protein-10 (BMP-10), Dickkopf WNT Signaling Pathway Inhibitor-3 (DKK-3), fibroblast growth factor-23 (FGF-23), angiopoietin-2 (Ang2), and fatty acid-binding protein-3 (FABP-3), all with electrochemiluminescence immunoassays (Roche Diagnostics, Germany). Results: We identified 236 patients with HFpEF, 156 with HFrEF, and 185 patients without HF with available plasma samples from 3680 patient records linked to echocardiographic DICOMs and blood samples. Patients with HFrEF and HFpEF had significantly higher median values of hs-cTnT, GDF-15, NT-proBNP, IGFBP-7, DKK-3, and FGF-23 than controls. The diagnostic accuracy (AUC) of NT-proBNP, hs-cTnT, GDF-15, IGFBP-7, and FABP-3 was >0.8 for identifying patients with HFrEF or HFpEF from controls. DL-algorithm-based interpretation of DICOM images provided further coverage of echocardiographic parameters relevant for diagnosis of HF subtypes. All biomarkers were associated with all-cause mortality and HF-related hospitalisation during a median follow-up of 1089 days. Conclusions: In this population-based study, we demonstrated a novel approach utilising a bioresource linked to a DL-supported pragmatic study to explore biomarkers in HF and demonstrated that multiple biomarkers to have diagnostic and prognostic significance for patients with HFrEF and HFpEF.

Abstract 11995: Contemporary Guideline-Directed Medical Therapy (GDMT) for Heart Failure is Associated With A Reduced Incidence of New-Onset Atrial Fibrillation

Backgrounds: Heart Failure (HF) is a risk factor for new-onset atrial fibrillation (AF), and the new-onset AF is associated with a worse prognosis in HF patients. It has been reported that renin-angiotensin system inhibitor (RASi), β-blocker, mineral-corticoid receptor antagonist (MRA) and Sodium-glucose cotransporter 2 inhibitors (SGLT2i) prevent the new-onset AF in HF patients. However, significance of contemporary guideline-directed medical therapy (GDMT) for HF (RASi/ARNI + β-blocker + MRA + SGLT2i) on new-onset AF is unknown. We investigated the impact of GDMT for HF on new-onset AF. Methods and Results: We retrospectively studied the long-term (The mean follow-up was 603 ± 410 days) incidence of new-onset AF in HFrEF and HFmrEF patients without episode of AF (n=410) admitted to our hospital due to decompensated HF between 2015 and 2022. Patients were divided into 2 groups; patients treated with ≦2 HF drugs (n=192) and patients with ≧3 HF drugs (n=218) after discharge. The incidence of new-onset AF was significantly fewer in the ≧3 HF drugs group (HR 0.36, 95%CI 0.16-0.82). A multivariate analysis revealed that ≧3 HF drugs use was an independent negative predictor of new-onset AF (HR 0.38, 95%CI 0.15-0.98, P=0.04). Even after a propensity score matching of clinical variables, the incidence of new-onset AF was consistently fewer in the ≧3 HF drugs group (HR 0.39, 95%CI 0.15-1.00, P=0.04). Finally, comparing between patients with and without new-onset AF, new-onset AF was significantly associated with re-hospitalization for HF (HR 5.41, 95%CI 3.32-8.89, P<0.001) and all-cause death (HR 2.36, 95%CI 0.98-5.68, P=0.047) in the studied population. Conclusion: The contemporary GDMT is associated with a reducing of new-onset AF in HF patients, which may be involved in the better outcomes with it.

Abstract 13656: Effects of Left Ventricular Ejection Fraction and NYHA CHF Class on Baroreceptor Function in Congestive Heart Failure

Background: Autonomic dysfunction is an important component in congestive heart failure (CHF) pathophysiology. The combined effects of reduced ejection fraction and advanced CHF Class on baroreceptor function in CHF have not been well investigated. Methods: A single center prospective study included 118 consenting patients, 68.3 ± 14.2 years old, 50 females (42.3%), BMI of 30.1 ± 8.5 kg/m 2 , with histories of HTN in 97 (82.2%), CAD in 64 (54.2%), diabetes in 49 (41.5%), and COPD or asthma in 39 (33.1%). Class I or II CHF were documented in 32 (27.1%), class III in 53 (44.9%), and class IV in 33 (28%) patients. Mean LV EF was 44.5+/-13.9%, HFrEF was present in 41 (34.7%) patients. Baroreceptor function was assessed by measuring resting and lowest heart rates (HR) during voluntary breath holding. Results: Despite treatment with beta-adrenergic blockers in 92 (78%) and non-dihydropyridine calcium channel blockers in 7 (5.9%) patients, increased CHF class was associated with significantly increased resting (71.7 ± 14.4 bpm in Class I-II, 73.1 ± 13.6 bpm in Class III, and 80.8 ± 16.9 bpm in Class IV, p=0.027) and breath holding HR (68.9 ± 15.3 bpm in Class I-II, 69.9 ± 12.2 bpm in Class III, and 80 ± 16.1 bpm in Class IV, p=0.002). In addition, when compared to the rest of the cohort, HFrEF patients manifested with increased resting (80.9 ± 14.5 vs. 71.6 ± 14.6 bpm, p=0.001) and breath holding HR (77.6 ± 13.9 vs. 69.7 ± 14.7 bpm, p=0.006). In multivariate analysis, both increased CHF NYHA class and reduced LVEF retained statistically significant independent effects on resting (p=0.037 and p=0.001, respectively) and breath holding HR (p=0.005, each). Conclusion: Decreased LV ejection fraction and increased CHF class independently and significantly contribute to autonomic dysfunction in CHF patients. Heart rate changes indicating abnormal baroreceptor function in CHF patients are apparent despite treatment with medications affecting chronotropic response.

Abstract 16521: Using Electronic Health Record Data to Identify and Prioritize Patients With Heart Failure With Reduced Ejection Fraction for a Remote Medication Optimization Program

Introduction: Remote medication management programs (RMMP) might be effective in optimizing guideline directed medical therapy (GDMT) for HFrEF. Identification of patients that can be safely managed remotely and prioritization of those with the highest need for medication optimization is crucial, especially in the setting of constrained resources. Methods: We analyzed records from our institutional enterprise data warehouse to identify patients with HFrEF in whom GDMT can be safely optimized by an RMMP within the Mass General Brigham health system between May 2021 and May 2023. After identifying a population with HFrEF, we excluded patients with contraindications to GDMT and with higher risk of adverse medication reactions. Next, we identified active and past medications by using medication discontinuation data (Figure). We performed chart review on a random sample of 100 patients to validate our analysis. Results: We have identified 1771 patients with HFrEF who are actively receiving care and are eligible for remote medication optimization. Only 7% (129/1771) of patients were prescribed all four GDMT, however in 4% (78/1771) at least one of these prescriptions was discontinued. Of all patients, 45% (801/1771) had stopped at least one GDMT, including 50% of SGLT2i, 30% of MRA, and 46% of ARNI. Patients who were never prescribed GDMT were identified as top priority for the RMMP. Conclusion: EHR data can effectively identify and prioritize HFrEF patients for medication optimization. Similar to prior HFrEF registries, our study showed poor utilization of GDMT. However, it also revealed a significant number of patients who had their GDMT prescriptions discontinued. Investigating the reasons for discontinuations may elucidate barriers to GDMT optimization. This study can be expanded to patients with HFpEF and HFmEF, and refined further by using natural language processing, machine learning, and by incorporating data for medication refill, claims, and dosages.

Abstract 17875: Quality Improvement Initiative to Improve Screening and Diagnosis Rates of Iron Deficiency in Patients Hospitalized for Acute Heart Failure With Reduced Ejection Fraction

Introduction: Despite being associated with reduced exercise capacity and poor quality of life in HFrEF, iron deficiency (ID) is underdiagnosed and undertreated. The 2022 ACC/AHA guidelines define ID in HFrEF as either a serum ferritin level < 100 ng/ml or 100-299 ng/ml with transferrin saturation (TSAT) <20 %. Treatment with IV iron is associated with a reduced risk of hospitalizations for HFrEF. A review of 20 inpatient acute HFrEF records revealed 10 had iron studies ordered, and 9 of them met criteria for ID, but only 1 patient received IV iron. Aim statement: To improve the testing rates for ID in hospitalized acute HFrEF patients at our hospital by 10% from January through March 2023. Methods: QI project included the implementation of an electronic health record (EHR) alert (Fig. 1) and resident education. The EHR alert was designed to be activated at the time of admission for patients with specific ICD codes for acute HFrEF to aid in ordering iron studies. A 20-minute educational session was delivered to residents, and handouts were provided to residents with reference material. Results: Pre-intervention data from January-December 2022 revealed a testing rate of 68% (154/194). ID was present in 58% (113/194). Post-intervention data from January 2023-March 2023 showed an improvement in the testing rate to 91% (67/73) and a concurrent increase in the diagnosis rate to 72% (53/73) (Fig. 2). Before discharge, 43.4% of patients (23/53) with ID received IV iron sucrose. Conclusion: Education and implementation of EHR alert were successful in increasing the testing rates for ID in acute HFrEF irrespective of anemia status. EHR tools should enhance sustainability compared to education alone.

Abstract 14872: A Nationwide Telehealth Heart Failure Program: Can Remote Patient Monitoring and Guideline Directed Treatment Protocols Benefit HFpEF Management?

Introduction: Heart failure (HF) patients experience unnecessary morbidity and mortality due to inadequate use and dose of GDMT. While RPM has proven to help HFrEF patients achieve higher rates of GDMT, its value in optimizing comorbidities and GDMT in HFpEF patients is less clear. Hypothesis: A team of multi-disciplinary HF clinicians can leverage RPM and guideline directed treatment protocols to bridge the gaps in HFpEF management. Methods: Cadence enrolled Medicare patients with HFpEF across 11 states into a virtual HF program from December 2021 to April 2023. Eligible patients had either an ICD-10 code for diastolic HF, diastolic dysfunction on TTE, or an EF>50% and a prior HFH or active treatment for HF by their clinician. Patients were given a cellular enabled BP cuff and weight scale to measure vitals. Coupling a technology enabled vitals and symptoms tracker with a guideline directed clinical protocol algorithm, symptom, vital and medication optimization was achieved. Results: Two-hundred fifteen patients (mean (SD) values: age 76 (9); white 64%, women 49%; BP 141/79 (9/6) mmHg; EF 60% (0.1)) were followed for a mean of 223 (82) days. Comorbidities, including DM (41%), AF (53%) and HTN (92%), were highly prevalent. There was a statistically significant reduction in BP and weight, but not heart rate (BP: -11/6 mmHg, Wt -4 lbs; p<0.001). Patient engagement information, including number of vitals recorded, clinical visits and phone calls completed, and high acuity clinical alerts resolved, is depicted in Figure 1A. There was a 286% and 71% increase in percentage of patients on a SGLT2i and MRA, respectively, at follow-up compared to baseline (SGLT2i: 15 (7%) vs. 44 (20%); p<0.001, MRA: 30 (14%) vs. 50 (24%); p<0.05). Additional changes in use and dose of GDMT are shown in Figure 1B. Conclusion: A telehealth HF program that utilizes RPM and technology enabled treatment protocols can meaningfully improve HF-specific vitals and rates of GDMT in patients with HFpEF.

Abstract 12503: Both Heart Failure With Reduced and Preserved Ejection Fraction Should Be Included in the CHA 2 DS 2 -VASc Score: A Taiwanese Longitudinal Cohort

Background: Congestive heart failure (CHF) is a known risk factor for atrial fibrillation (AF)-related thromboembolic stroke. The CHA2DS2-VASc score incorporates CHF but was developed when it primarily referred to patients with reduced ejection fraction (HFrEF). CHF now includes preserved ejection fraction (HFpEF) patients. Therefore, the distinction between stroke risk of AF patients with HFpEF and HFrEF is important for improving risk assessment and management strategies for AF patients. Methods: In a longitudinal study utilizing the National Taiwan University Hospital Integrated Medical Database (iMED), 8358 patients with atrial fibrillation (AF) were followed from January 2010 to December 2020 (mean follow-up 3.76 years). Among these patients, 4654 (55.7%) had no history of CHF, 2374 (28.4%) had HFpEF, and 1330 (15.9%) had HFrEF. HFpEF was defined as patients with a left ventricular ejection fraction (LVEF) of 55% or higher. The study evaluated the risk of ischemic stroke using Cox models adjusted for all components of the CHA2DS2-VASc score. Results: Patients with HFpEF were older, more frequently female, and had a higher prevalence of previous stroke and hypertension. They also had a higher mean CHA2DS2-VASc score (4.08±1.502 vs. 3.83±1.571, p<0.001) and a higher risk of stroke compared to HFrEF patients (30.1% vs 26.3%, p=0.014). After adjusting for other stroke risk factors with CHA2DS2-VASc score components, there was no significant difference in the risk of stroke between the HFpEF and HFrEF groups (p=0.799). Conclusion: Both HFpEF and HFrEF were associated with a higher risk of stroke. Thus, the criteria of "CHF" in the CHA2DS2-VASc score should include HFpEF as well.

Abstract 14596: Differences in Healthcare Resource Utilization Among Patients Receiving Comprehensive Guideline-Directed Medical Therapy by Prior History of Worsening Heart Failure Events

Background: Heart failure (HF) is a leading cause of hospitalizations in the US. While Guideline-Directed Medical Therapy (GDMT) improves outcomes in patients with heart failure with reduced ejection (HFrEF), healthcare resource utilization (HCRU) among patients with worsening heart failure (WHF) has not been well characterized. Aim: We compare HCRU by history of WHF at initiation of “2022 GDMT” (i.e., ARNi+β-blocker+MRA+SGLT2i). Methods: Patients with HFrEF who had concurrent exposure for ARNi, SGLT2i, β-blocker, and MRA between Jan 2020-Jun 2022 were identified using Optum’s deidentified Clinformatics® Data Mart Database. HCRU (i.e., all-cause hospitalizations [ACH] and HF hospitalizations [HFH]) was compared by history of WHF (i.e., HFH or IV diuretic administration) in the prior 12 months. Cox proportional hazard and negative binomial regressions estimated factors independently associated with risk of first and recurrent hospitalizations and their durations, respectively. Results: The analytical cohort included 3,881 HFrEF patients receiving 2022 GDMT, 1,835 (47%) with a prior history of WHF. Patients with and without a history of WHF had similar sociodemographic characteristics. The median (IQR) follow-up time was 352 (244, 544) days for the cohort. Patients with WHF were hospitalized sooner, more frequently, and for a longer duration of time ( Table ) compared to those without. After adjusting for sociodemographic characteristics, WHF was independently associated with longer length of stay of ACH (coefficient, 95% CI: 1.91, 1.59-2.31) and HFH (2.13, 1.74-2.61) and almost three times the risk of first and recurrent ACH (HR, 95% CI: 2.93, 2.64-3.26) and HFH (2.93, 2.61-3.29). Conclusion: Prior history of WHF was associated with clinically meaningful and statistically significant worse HCRU, despite first-line “2022 GDMT”. Additional care strategies and novel therapies are required to further decrease residual risk among these patients.

Abstract 17378: A Novel Strategy in the Sequencing of HFrEF Therapy: An Upfront and Prompt Approach

Introduction: The latest HF European guidelines recommend the use of four different classes of drugs for HFrEF. Despite advances in treatment, some gaps remain to be filled. In particular, sequencing and timing of HF therapy administration are not clarified and different strategies have been proposed. Hypothesis: An early, upfront novel approach, based on prompt administration of BB, SGLT2i, ACEi/ARNI, and MRAs may prove beneficial in terms of HF rehospitalization and CV death risk reduction. Aims: To compare early sequencing of HFrEF GDMT with the conventional, stepwise strategy. The primary endpoint was a composite of HF rehospitalization and CV death. Secondary endpoints were the single events of the primary endpoint. Methods: This prospective, observational study included consecutive patients with a HFrEF diagnosis from the Cardiology department. They were divided based on treatment strategy. Group 1 (G1) was treated with a novel GDMT sequencing (in-hospital start of BB and SGLT2i, ACE-i/ARNI, and lastly adding MRAs within 30 days from discharge). Group 2 (G2) was treated with the conventional, stepwise GDMT sequencing. Comparison between the two groups has been performed at 6-month follow up. Results: The study included a total of 302 patients. 278 patients underwent follow up: 139 in G1 group and 139 in G2 group. The two groups did not show significant differences at baseline. No significant differences have been observed for the primary composite outcome (p= 0.135) and for CV mortality (p=0.642) between the two groups. HF rehospitalization risk was significantly lower in G1 group compared to G2 group (p<0.001). Conclusions: HFrEF patients treated with a novel GDMT sequencing, promptly initiated and completed within 30 days from discharge, have shown reduced risk of HF rehospitalization compared with the conventional strategy.

Abstract 19069: Empagliflozin Improves Right Ventricular Remodeling and Right Ventricular Systolic Function in Non-Diabetic Hfref: Insights From Porcine and Human Studies

Background On top of improving heart failure outcomes, we and others have demonstrated that SGLT2 inhibitors induce reverse cardiac remodeling in HFrEF. However, these studies have focused on the left ventricle, while no information is available on the potential benefits of SGLT2i on the right ventricle (RV). Therefore, our objective is to investigate the effect of empagliflozin on RV remodeling and RV systolic function in non-diabetic HFrEF Methods Animal study: HFrEF was induced by means of proximal LAD occlusions for 2 hours in non-diabetic pigs. Pigs were then randomized to empagliflozin 10mg daily or placebo for 2 months (8/group). Pigs were evaluated with cardiac MRI. We previously reported that empagliflozin reduces LV volumes and improve LVEF (Santos-Gallego, JACC 2019) Human study : The EMPATROPISM clinical trial ((NCT03485222) randomized non-diabetic HFrEF patients to empagliflozin 10mg daily or placebo. All patients were evaluated with MRI. We previously reported that empagliflozin reduces LV volumes, while also improving peakVO2, LVEF, and quality of life (Santos-Gallego, JACC 2021) Results Animal study: Both groups were similar at baseline (RVESV 16.1±3.2 vs 15.8±2.1mL; RVEF 51.9±5.6 vs 52.7±4.7%; p=NS). Cardiac MRI showed that empagliflozin-treated pigs exhibited smaller RVEDV and RVESV at 2 months compared with control. Also treated animals exhibited better RVEF and better right ventriculoarterial coupling (Ees/Ea) vs control (Table) Human study: Both groups were similar at baseline (RVESV 87.4±35.6 vs 76.4±32.4 mL; RVEF 47.1±7.9 vs 49.2±9.1%; p=NS). Cardiac MRI showed that empagliflozin-treated patients experienced a reduction in RVESV vs placebo. Furthermore, empagliflozin-treated patients exhibited improvement in RVEF and in right ventriculoarterial coupling (Ees/Ea) vs control (Table) Conclusions Empagliflozin improves right ventricular remodeling and right ventricular systolic function in non-diabetic HFrEF

Abstract 15401: Artificial Intelligence-Enabled Exercise-CMR for Evaluation of Cardiac Functional Reserve in Heart Failure

Introduction: Exercise unmasks pathophysiological markers in heart failure (HF), not evident at rest. Exercise CMR (Ex-CMR) has the potential to offer an accurate and reproducible assessment of cardiac functional reserve in HF. Objective: To study the cardiac functional reserve in HF using an artificial intelligence (AI) enabled exercise CMR imaging protocol. Method: We prospectively recruited patients with an established clinical diagnosis of HF and healthy adults. Subjects were imaged at rest and immediately post-exercise using a supine ergometer positioned on the CMR scan. The imaging protocol included free-breathing, real-time, highly accelerated cine short-axis images covering the entire LV. Cine images were collected with a spatial resolution of 1.9 х 1.9 mm 2 and temporal resolution of 38.8 ms using a 14.8-fold acceleration using an in-house inline deep learning reconstruction. Pre- and post-exercise biventricular volumetric and functional parameters and their corresponding percentage changes were calculated. Results: The study included 77 subjects, consisting of 37 HF patients (24 males; 60 ± 12 years) [HFpEF, n=13; HFmrEF, n=5; HFimpEF, n=13; and HFrEF, n=6], and 40 healthy adult (20 males; 45 ± 16 years). Changes in LV end-diastolic and end-systolic volume among subgroups revealed distinct clusters (Fig 1). These findings corresponded to a blunted to a modest rise in stroke volume (SV) observed in HFpEF and HFmrEF patients, respectively, while HFimpEF and HFrEF patients exhibited a mildly to excessively higher SV rise compared to other subgroups (Fig 1). HFpEF and HFmrEF showed no improvement in SV index beyond 10 ml/m 2 . Patients with known post capillary pulmonary hypertension demonstrated an inadequate right ventricle response in preload recruitment, contributing to a blunted increase in RV SV (Fig 1). Conclusion: Our AI-enabled, high-accelerated Ex-CMR imaging protocol reveals a distinctive biventricular functional reserve response in HF.

Evaluation of β-blockers dosage regimen rationality in heart failure patients

Background: β-Blockers are often associated with further cardiac function deterioration, ledding to them being often underused/underdosed by certain physicians in heart failure treatment, although they were seen to be beneficial in decreasing the rates of mortality and morbidity, duration of hospitalization in HFrEF patients, but data on their benefits in HFmEF and HFpEF patients is limited. Objective was to evaluate rationality of β-blockers’ dosage regimen and its effectiveness in HF patients. Methods: 43 HF patients have been enrolled. Data were collected from the medication chart (dose, route, frequency); dosage regimen was evaluated and compared to that of ESC guidelines for HF treatment. Heart rates pre/post drug treatments, ejection fraction (at admission & post-discharge) were recorded; effectiveness was evaluated through heart rate control, reduction in: duration of hospitalization, rehospitalization and mortality rate. Post-discharge updates of the patients were obtained through out-patient consultation reports. Results: In All 43 patients dosage regimen of selected β-Blockers was found to be rational and following the ESC guideline for HF treatment. 65% of patients spent not more than 5 days in the hospital, 16% Re-hospitalized for cardiovascular diseases, and death rate was 4%. Conclusions: The dosage regimen of selected β-Blockers was found to be as per that of ESC-guidelines HF treatment. β-Blockers have also been found to have reduced: hospitalization stay, frequency of rehospitalization, and death rate among patients under study.

Role of ejection fraction in patients at risk for advanced heart failure: insights from the HELP-HF registry.

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. 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% and 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±11.5years, 67.3% males, 67.6% hospitalized, median follow-up 260days (inter-quartile range 105-390days)], HFrEF, HFmrEF, and HFpEF were observed in 699 (60.8%), 122 (10.6%), and 328 (28.6%) patients, and 1year 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<50% and EF≥50% groups. Among patients with HF and at least one 'I NEED HELP' marker for advanced HF, left ventricular EF is still of prognostic value.

Echocardiographic mechanical dyssynchrony predicts long-term mortality in patients with cardiac resynchronisation therapy

Cardiac resynchronisation therapy (CRT) is an established treatment for patients with symptomatic heart failure with reduced left ventricular ejection fraction (LVEF ≤ 35%; HFrEF) and conduction disturbances (QRS duration ≥ 130 ms). The presence of mechanical dyssynchrony (MD) on echocardiography has been hypothesised to be of predictive value in determining indication for CRT. This study investigated the impact of MD (apical rocking [AR] and septal flash [SF]) on long-term survival in CRT recipients. HFrEF patients (n = 425; mean age 63.0 ± 10.6 years, 72.3% male, 60.7% non-ischaemic aetiology) with a guideline-derived indication for CRT underwent device implantation. MD markers were determined at baseline and after a mean follow-up of 11.5 ± 8.0 months; long-term survival was also determined. AR and/or SF were present in 307 (72.2%) participants at baseline. During post-CRT follow-up, AR and/or SF disappeared in 256 (83.4%) patients. Overall mean survival was 95.9 ± 52.9 months, longer in women than in men (109.1 ± 52.4 vs. 90.9 ± 52.4 months; p < 0.001) and in younger (< 60 years) versus older patients (110.6 ± 53.7 vs. 88.6 ± 51.1 months; p < 0.001). Patients with versus without MD markers at baseline generally survived for longer (106.2 ± 52.0 vs. 68.9 ± 45.4 months; p < 0.001), and survival was best in patients with resolved versus persisting MD (111.6 ± 51.2 vs. 79.7 ± 47.6 months p < 0.001). Age and MD at baseline were strong predictors of long-term survival in HFrEF patients undergoing CRT on multivariate analysis. Novel echocardiography MD parameters in HFrEF CRT recipients predicted long-term mediated better outcome, and survival improved further when AR and/or SF disappear after CRT implantation.Graphical abstract

Impact of Body Mass Index on outcomes in hospitalized heart failure patients with reduced versus preserved ejection fraction: a 1,699,494-individual analysis from the United States National Inpatient Sample.

Obesity's effect on outcomes in heart failure (HF) patients with reduced versus maintained ejection fraction (HFrEF and HFpEF) remains debatable. We evaluated hospital outcomes and healthcare expenditures in these patients based on their Body Mass Index (BMI). Using the USA National Inpatient Sample (NIS) database, patients >18 years admitted with a primary diagnosis of HFrEF or HFpEF between January 1, 2004, and August 31, 2015, were studied. Patients were stratified into the following BMI categories: underweight, normal weight, overweight, obese, and morbidly obese. Adjusted multivariable analyses using Poisson regression models were used to study the association between BMI and hospital outcomes and healthcare costs. Overall, 1,699,494 patients were included. After full adjustment, obesity (OR=1.84; 95% CI: 1.22-2.76) and morbid obesity (OR=1.81; 95% CI: 1.22-2.70) increased the odds of in-hospital mortality compared with normal weight. When stratified per ejection fraction, underweight patients had higher odds of in-hospital mortality in HFrEF (OR=1.46; 95% CI: 1.06-2.01). Obese and morbidly obese patients had higher odds of in-hospital mortality in both HFrEF and HFpEF. Furthermore, obese and morbidly obese patients had a longer mean adjusted length of stay and higher health care expenses. Being underweight is associated with increased risk of in-hospital mortality in HFrEF patients. Obesity and morbid obesity increase the risk of in-hospital mortality and higher healthcare costs in both HFrEF and HFpEF. These findings have clinical significance for HF patients, and further research is needed to investigate the ideal weight for HF patients.

FGF-23 is a biomarker of RV dysfunction and congestion in patients with HFrEF

There is no biomarker reflecting right ventricular dysfunction in HFrEF patients used in clinical practice. We have aimed to look for a circulating marker of RV dysfunction employing a quantitative proteomic strategy. The Olink Proteomics Multiplex panels (Cardiovascular Disease II, III, Cardiometabolic, and Inflammation Target Panels) identified FGF-23 to be the most differentially abundant (more than 2.5-fold) in blood plasma of HF patients with severe RV dysfunction (n = 30) compared to those with preserved RV function (n = 31). A subsequent ELISA-based confirmatory analysis of circulating FGF-23 in a large cohort of patients (n = 344, 72.7% NYHA III/IV, LVEF 22.5%, 54.1% with moderate/severe RV dysfunction), followed by multivariable regression analysis, revealed that the plasma FGF-23 level was most significantly associated with RV dysfunction grade (p = 0.0004) and congestion in the systemic circulation (p = 0.03), but not with LV-ejection fraction (p = 0.69) or estimated glomerular filtration rate (eGFR, p = 0.08). FGF-23 was associated with the degree of RV dysfunction in both sub-cohorts (i.e. in patients with and without congestion, p < 0.0001). The association between FGF-23 and RV-dysfunction remained significant after the adjustment for BNP (p = 0.01). In contrast, when adjusted for BNP, FGF-23 was no longer associated with LV dysfunction (p = 0.59). The Cox proportional hazard model revealed that circulating FGF-23 was significantly associated with adverse outcomes even after adjusting for BNP, LVEF, RV dysfunction grade and eGFR. Circulating FGF-23 is thus a biomarker of right ventricular dysfunction in HFrEF patients regardless of congestion status.

Application status of guideline-directed medical therapy in HFrEF patients and improvement strategies

Application status of guideline-directed medical therapy in HFrEF patients and improvement strategies