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Peak oxygen consumption (V̇O2peak) is used to predict outcomes and time to transplantation in patients with heart failure with reduced ejection fraction (HFrEF); V̇O2peak also has predictive utility in patients with adult congenital heart disease (ACHD). However, the predictive value of a given V̇O2peak on cardiac events in patients with ACHD compared to HFrEF, especially after adjustment for age and sex, is unclear. Therefore, we performed a longitudinal cohort study comparing patients with ACHD to patients with HFrEF. The cohorts were sex and age matched (±10 years). V̇O2peak tests were conducted from 1993 to 2012. Cardiac events included death, cardiac transplantation, and LVAD placement. Events were obtained via electronic medical record, SSDI, and phone interview. Cox proportional-hazard regression analyses were used to evaluate relationships of event-free survival with predictor variables. Patients with ACHD (N = 137) and HFrEF (N = 137) had median follow-up times of 19.0 years (14.8 to 21.1) and 14.5 years (13.4 to 15.6), respectively. In multivariable models, Higher V̇O2peak was associated with lower risk for a cardiac event, independent of age and sex, in both ACHD (HR 0.89, 95% CI 0.83 to 0.96, p = 0.002) and HFrEF (HR 0.86, 95% CI 0.82 to 0.91, p <0.001). Male sex was associated with greater risk of a cardiac event HFrEF (HR 1.90, 95% CI 1.24 to 2.90, p = 0.003) but not in ACHD group. After multivariable adjustment (Beta-blockers, sex, and V̇O2peak), having ACHD conferred a 71% lower risk of cardiac events compared to a HFrEF diagnosis (HR 0.29, 95% CI 0.18 to 0.47, p <0.001). V̇O2peak independently predicts event-free survival among adults with ACHD or HFrEF and has clinical utility in outpatient settings. Patients with ACHD have a better prognosis after multivariable adjustment including V̇O2peak compared to HFrEF.

BackgroundAddressing racial differences in care delivery is one of the current challenges in the diagnosis and treatment of patients with Heart Failure (HF). Compared to Caucasians, patients from minority racial groups with HF and reduced Ejection Fraction (HFrEF) are less likely to receive evidence-based, medical, device or advanced therapies. However, there is a lack of contemporary, nationwide data on racial differences in in-hospital quality of care and long-term outcomes for patients with HFrEF. This analysis aims to investigate racial disparities in the quality of care and long-term outcomes of patients with HFrEF in the UKMethodsWe used linked, routinely collected data from 3 large national UK registries (the National Heart Failure Audit, Hospital Episode Statistics, and the Office for National Statistics) from 2020 to 2022 to investigate care and outcomes for patients with HF. We compared clinical characteristics and long-term events of interest according to self-reported race. A multivariable Cox proportional hazard model was performed adjusting for age, sex, comorbidity profile and clinical characteristics at admission.ResultsA total of 59,727 patients with HFrEF were analysed. At admission, white patients were generally older compared to other ethnicities (79 years [IQR 69;86] for white, 67 years [IQR 56;82] for black, 73 years [IQR 63;82] for Asians, 76 years [IQR 64;85] for mixed race and 73 years [IQR 60;83] for other races, p<0.001). Overall, approximately two-thirds of patients were men (64%, n=38,432), 78% (n=44,425) were admitted in NYHA class III or IV, and approximately half of the patients (49%, n=27,731) presented with moderate to severe peripheral oedema, without clinically meaningful differences between races. In-hospital care was similar between races, as were rates of guideline-recommended medications at discharge (70%, n=36,913 for renin-angiotensin-aldosterone system inhibitors; 84%, n=44,611 for beta-blockers; 52%, n=24,105 for mineralocorticoid receptor antagonists; 88%, n=44611 for diuretics). Over a median follow-up of 71 weeks [IQR 23;146], in an unadjusted analysis, mortality was higher for white patients compared to other races (p<0.001, Figure 1). However, on multivariable analysis, white race was not an independent predictor of adverse outcomes (HR 1.07; 95% CI 0.93 – 1.24; p=0.30).ConclusionFor patients hospitalised with HFrEF in England & Wales, in-hospital quality of care and the percentage of patients discharged on guideline-recommended medications are similar amongst different races. Although post-discharge mortality was higher for white patients, after adjustment, white race was not an independent predictor of adverse events.Abstract 131 Figure 1Race differences in HFrEFConflict of Interestnone

BackgroundRecent landmark trials such as DAPA-HF and EMPEROR-Reduced have led to the approval and implementation of Sodium/glucose cotransporter 2 (SGLT2) inhibitors as a first line therapy for heart failure with reduced ejection fraction (HFreF). However, there is a paucity of data looking at real world outcomes in heart failure patients.AimWe sought to evaluate the real-world outcomes of SGLT2 inhibition in our local HFreF population. MethodWe performed a retrospective data analysis of patients with HFrEF commenced on a SGLT2 inhibitor since September 2021. The primary composite endpoint of heart failure hospitalisations and cardiovascular (CV) death was assessed six months from initiation with historical matched controls as comparators. Secondary endpoints included change in New York Heart Association (NYHA) score and change in serum creatinine at six months. Data were extracted from local healthcare records. Data expressed as mean+/-standard deviation with p<0.05 defined as significant. Variance between groups analysed using students t test. Statistical analysis performed with SPSSTM. Results112 patients were commenced on SGLT2 inhibition (dapagliflozin n=99, 97%, empagliflozin n=3, 3%). The mean age was 66.6+/-14.6 years (59%, male n=66) with a mean LVEF at baseline of 28.4+/-14.7%. The predominant aetiology of heart failure was ischaemic (n=71, 64%) with 17% of patients being diabetic (n=19). In patients with HFreF commenced on SGLT2 inhibition, at six months, there was a significant reduction in the primary composite endpoint compared to controls (p=0.04) (Figure 1). There was a significant difference in CV mortality compared to controls (2 vs 11, p<0.01) with a lower number of heart failure hospitalisations in the SGTL2 groups (34 vs 43); however, this did not reach statistical significance (p=0.06). There was a significant reduction in mean NYHA score following initiation of an SGLT2 inhibitor (2.15+/-0.89, n=112 to 1.93+/-0.77, n=109; p<0.01). Renal parameters including serum creatinine initiation (105.5+/-31umol/L vs 90+/-38umol/L, p=ns) and potassium (4.5+/-0.48 mmol/L vs 4.7+/-0.61 mmol/L, p=ns) remained stable at six months.Abstract 122 Figure 1Heart failure hospitalisations and CV death at six months following SGLT2 inhibition compared to historical controls. There was a significant reduction in the combined composite endpoint of HF hospitalisation and CV death in the SGLT group vs controls (36 vs 54, n=112; p=0.04). There was a significant reduction in CV death in the SGLT2 group vs control (2 vs 11, n=112; p<0.01). A reduction in heart failure hospitalisations was noted; however, this did not reach clinical significance (34 vs 43, n=112; p=/ns)ConclusionIn a real-world population of HFreF patients, SGTL2 inhibitors produce a statistically significant reduction in heart failure hospitalisations and CV death with a significant reduction in QOL outcomes measured by NYHA score. Furthermore, parameters of renal function remained stable following initiation of SGLT2 inhibition.Conflict of Interestnone

IntroductionPharmacotherapy is the cornerstone of treatment for symptomatic and prognostic improvement in heart failure with reduced ejection fraction (HFrEF). Angiotensin-converting enzyme inhibitors or angiotensin receptor/neprilysin inhibitors, beta-blockers, mineralocorticoid receptor antagonists and sodium-glucose co-transporter 2 inhibitors have been shown to provide incremental benefit with marked reduction in mortality and morbidity. Studies have suggested early and rapid titration of all 4 classes of drugs would lead to earlier prognostic improvement, especially in the high-risk period after an acute decompensation. Nonetheless, a significant proportion of patients with HFrEF are either not on an appropriate combination of medications nor optimal doses of medications. We therefore hypothesized that an aggressive and rapid strategy aimed at initiation of all 4 classes of drugs in a four-week period would be feasible and safe. Method - Patients were recruited in our study over a 4-month period. Consecutive patients presenting with a de novo exacerbation of HFrEF (defined as severe left ventricular systolic dysfunction, EF<40% as per ESC guidelines) either in the community or following hospitalization were included in the study. All were followed up in a hospital-based heart failure clinic. Patients were seen either by a heart failure specialist consultant or a senior heart failure nurse. No specific predetermined pathway was mandated and clinicians made individual decisions regarding the sequence of drug initiation on a case by case basis. Blood pressure, heart rate and renal function was monitored at each appointment. Results - A total of 101 patients were enrolled. 19 were deemed unsuitable for the rapid initiation pathway prior to the initial assessment. Out of 82, 32 (39%) had limitations to the initiation of HFrEF medications at the outset. In 50 who were deemed suitable for initiating all 4 drugs, 38 (76%) were able to successfully complete the ‘4 x 4’ strategy. 3 (6%) in this group had significant adverse events during the follow up (symptomatic hypotension, hyperkalaemia and renal function decline).Abstract 123 Table 1Baseline characteristic of enrolled patients. *=Median **=MeanConclusion- Population baseline characteristics would suggest a relatively high-risk group of patients (i.e. high NT-Pro BNP, high incidence of AF and higher age). This observational real world study has demonstrated that an early and rapid titration is achievable in a majority of patients. The rate of significant adverse effects was low. The delay in initiating SGLT-2 inhibitor medication in diabetic patients would suggest that we need a more streamlined pathway for this group of patients. In order to deliver this service for 82 patients, we needed to have 12 clinic appointments per week for the 4-month period. This has obvious resource implications but arguably, early‘front loading’ would lessen the subsequent need for long term specialist input.Conflict of InterestNone

IntroductionGuideline-directed medical therapy (GDMT) has unequivocal mortality benefits in patients with heart failure with reduced ejection fraction (HFrEF). However, real world studies show that their uptake is often limited due to concerns of adverse effects.ObjectiveTo synthesise an evidence-based approach to implement and up-titrate GDMT in HFrEF patients with hypotension, hyperkalaemia and poor renal function.MethodsWe reviewed major HF guidelines (2021 ESC Guideline, 2023 Focused Update of 2021 ESC Guideline & 2022 AHA/ACC/ HFSA Guideline) for practical guidance on use of GDMT. We also studied the inclusion and exclusion criteria, and adverse effect profiles of foundational drugs [angiotensin converting enzyme inhibitor (ACEI), angiotensin receptor blocker (ARB), angiotensin receptor/neprilysin inhibitor (ARNI), beta-blocker (BB), mineralocorticoid receptor antagonist (MRA) and sodium-glucose co-transporter 2 inhibitor (SGLT2I)] in contemporary landmark trials. Pharmacological properties of the individual drugs were also considered.ResultsPatients with asymptomatic hypotension [systolic blood pressure (SBP) < 100 mmHg] can be initiated on SGLT2I and low dose BB (preferably metoprolol succinate), given their weak BP lowering effects. It is reasonable to start BB therapy early in the diagnosis of HF as it confers beneficial effects in reducing sudden cardiac death. SGLT2I has diuretic property and may enable reduction of loop diuretics, thus improving BP. In subsequent visits, depending on patients’ tolerability, low dose MRA could be initiated (preferably eplerenone) as they have less BP lowering effect than ACEI/ARB. ARNI has stronger hypotensive effect than ACEI/ ARB and best avoided in this case (figure 1).In patients with hyperkalaemia, counselling on low potassium diet is paramount. If potassium remains persistently > 5.5 mmol/L, initiation of potassium binders (e.g., sodium zirconium cyclosilicate & patiromer) is warranted. In these patients, BB and SGLT2I can be initiated in the first step. SGLT2I, with its diuretic effect, may help to reduce potassium level further. ARNI can be initiated next, provided potassium is controlled (< 5.5 mmol/L), followed by eplerenone (lower hyperkalaemic effect than spironolactone), with continued use of potassium binders to maintain MRA therapy.Patients with eGFR < 30 mL/min/1.73 m2 may not achieve all 4 foundational therapies, as MRA is contraindicated. However, in those with eGFR 20–30 mL/min/1.73 m2, BB, ACEI/ARB/ARNI and SGLT2I (Empagliflozin) are safe to be administered. For patients with eGFR < 20 mL/min/1.73 m2, BB and ACEI/ARB could be used; however, there is a lack of safety data on ARNI and SGLT2I use in this population.ConclusionHypotension, hyperkalaemia and poor renal function are significant clinical barriers that contribute to underutilisation of GDMT. Adopting evidence-based strategies using an individualised approach to initiate and up-titrate medications may help overcome therapeutic inertia and optimise the management of patients with HFrEF.Abstract 170 Figure 1Evidence-based algorithm to initiate and up-titrate GDMT in HFrEF patientsConflict of InterestNone

IntroductionDespite evidence-based pharmacological recommendations, many patients with HFrEF remain undertreated.1 In part this is due to inertia, with patients often being described as “stable” as they have minimal symptoms, and they may even have been discharged from regular clinical follow-up. Nevertheless, these patients remain at risk of decompensation and might benefit treatment optimisation. Many patients may also have been diagnosed with HFrEF prior to the use of sacubitril/valsartan or SGLT2 inhibitors. Identification of patients with historical HF diagnosis is time-consuming, often requiring manual case note review. Artificial intelligence approaches using deep learning might allow rapid identification of such patients.AimThe aim of this study was to develop an artificial intelligence deep-learning algorithm for rapid identification of HF from electronic health records (EHRs) and to determine the potential benefit of our AI-driven algorithm for the detection of undertreated HFrEF patients in the community.MethodologyIn this study data was collected from EHRs of 1,200 patients who underwent transthoracic echocardiography. The records were screened to identify HF diagnosis through an AI deep-learning algorithm using a Convolutional Neural Network (CNN). Medication status of patients identified as having HFrEF was assessed to determine whether they were on optimal guideline-directed medical therapy. Accuracy of the AI algorithm was assessed by a manual clinician review in a subset of 150 patients. Eligible patients not on optimal medical therapy where no further optimisation was planned (judged to be “stable” at last visit) were invited for a clinical evaluation including NT-proBNP and Kansas City Cardiomyopathy Questionnaire (KCCQ) and offered a treatment optimization that could include either uptitration or initiation of a new medication if symptomatic. NT-proBNP and KCCQ were repeated at 12 week, pre- and post-optimization results were compared to evaluate patient outcomes.ResultsThe deep-learning algorithm accurately identified HFrEF patients (99%) and use of RAAS inhibitors (97%) and beta-blockers (92%). 73 patients attended for initial clinical assessment (mean age 70 years, 77% male) and demonstrated a moderate level of HF-symptom burden (median NT-proBNP was 679 pg/mL, interquartile range was from 220 to 1300) and mean KCCQ overall summary score was 70, indicating a moderate level of HF symptom burden. 27 patients agreed to treatment optimisation. After 12 weeks there was a significant 22% reduction in NT-proBNP (from 1991 pg/mL (SD+/- 1796) to 1630 pg/mL (SD +/- 1588),p=0.049) and improvements in KCCQ (total symptom score 79 (+/-22) to 85 (+/-20), p=0.005; clinical summary score 78 (+/-23) to 82 (+/-20); overall summary score from 75 (+/- 24) to 80 (+/-22), both p=0.04). 23 patients (85%) and 18 patients (67%) out of 27 had an improvement in NT-proBNP and KCCQ overall summary scores respectively.ConclusionIn our study we demonstrated the feasibility and potential benefits incorporating AI into a clinical workflow, allowing optimising treatment of patients with HF, with improvements in biomarkers and quality of life that could translate to long-term patient benefits.ReferenceTarget Doses of Heart Failure Medical Therapy and Blood Pressure: Insights From the CHAMP-HF Registry https://doi.org/10.1016/j.jchf.2018.11.011Conflict of InterestNoAbstract 143 Figure 1Abstract 143 Figure 2Abstract 143 Figure 3

IntroductionHeart failure with reduced ejection fraction (HFrEF) increases the risk of sudden cardiac death (SCD). ESC and NICE guidelines recommend primary prevention implantable cardioverter-defibrillator (ICD) for HFrEF patients with an LVEF ≤35% despite 3 months of optimised medical therapy (OMT). Recommendations are primarily based on data from MADIT II and SCD-HeFT. However, OMT in these trials was suboptimal by current standards. Further, several studies have shown improvements in LVEF with longer OMT. If LVEF improves with newer/longer OMT, ICD implantation may be avoidable for many patients. Consideration must be given to the safety of delaying ICD implantation. However, the absolute risk reduction of mortality in MADIT II and SCD-HeFT was only 1% at 12 months (0% for patients with DCM).We assessed the impact of longer duration OMT on LV function and ICD therapy rates in patients who have already undergone guideline-directed ICD implantation.MethodsThis is a multi-centre, observational study enrolling adults with HFrEF. Patients had to have been treated with OMT for ≥3 months at the time of ICD implantation, and for between 12 and 24 months at the time of reassessment. Patients with cardiac resynchronisation therapy or an indication for RV pacing were excluded. Approval was obtained from local and national ethics committees. Two timepoints were compared, baseline (3 months of OMT) and follow-up (12–24 months of OMT).Main outcomesproportion of participants with LVEF >35% after ≥12 months of OMTappropriate and inappropriate ICD therapycomplications secondary to ICD implantationResultsSince January 2022, 26 patients have been recruited. Baseline characteristics are shown in table 1. The mean duration of OMT at follow-up was 547 days (122). At baseline, mean LVEF was 28.4% (4.7) (figure 1). At follow-up, mean LVEF increased to 33.9% (5.8) (figure 1) and 8 patients (31%) had an LVEF of >35%.1 patient required a lead revision for RV lead displacement. 1 patient had their ICD explanted due to suspected infection. Only 1 patient received appropriate therapy from their ICD, receiving anti-tachycardia pacing (ATP) for VT 583 days post-implant. 1 patient received both an inappropriate shock and inappropriate ATP. 1 patient received an inappropriate shock and 1 patient received inappropriate ATP.ConclusionsWe found that 31% of patients no longer met the indications for a primary prevention ICD after a longer duration of OMT. If ICD implantation were delayed many patients could avoid ICD implantation altogether. Further, rates of appropriate ICD therapy were low; within the first 12 months after ICD implant no patients received appropriate therapy from their device. This suggests that the risk of ventricular arrhythmias is low and it may be safe to delay primary prevention ICD implantation until patients have been on OMT for a longer duration.However, our study is limited by small numbers. We plan to continue recruitment to reach target of 50 patients.Abstract 110 Table 1Baseline characteristics (3 months of OMT) Baseline characteristics n=26 Age, mean (SD) 66.2 years (6.6) Aetiology of heart failure:- Ischaemic heart disease, n (%) 18 (69.2) Heart failure medications ACE inhibitors, n (%) 9 (34.6) Angiotensin receptor blockers, n (%) 2 (7.7) Sacubitril/valsartan, n (%) 15 (57.7) Beta-blockers, n (%) 26 (100) Mineralocorticoid receptor antagonists, n (%) 15 (57.7) SGLT2 inhibitors, n (%) 19 (73.1) Abstract 110 Figure 1Box and whisker plot comparing mean LVEF at baseline (3 months of OMT) and follow-upConflict of InterestNone

Sodium-glucose co-transporter 2 inhibitors (SGLT2i) are emerging as a new treatment strategy for heart failure with reduced ejection fraction (HFrEF) and—depending on the wistfully awaited results of two clinical trials (DELIVER and EMPEROR-Preserved)—may be the first drug class to improve cardiovascular outcomes in patients suffering from heart failure with preserved ejection fraction (HFpEF). Proposed mechanisms of action of this class of drugs are diverse and include metabolic and hemodynamic effects as well as effects on inflammation, neurohumoral activation, and intracellular ion homeostasis. In this review we focus on the growing body of evidence for SGLT2i-mediated effects on cardiac intracellular Na+ as an upstream mechanism. Therefore, we will first give a short overview of physiological cardiomyocyte Na+ handling and its deterioration in heart failure. On this basis we discuss the salutary effects of SGLT2i on Na+ homeostasis by influencing NHE1 activity, late INa as well as CaMKII activity. Finally, we highlight the potential relevance of these effects for systolic and diastolic dysfunction as well as arrhythmogenesis.

Elevated pro-inflammatory biomarkers and cytokines are associated with morbidity and mortality in heart failure (HF). Preclinical and clinical studies have shown multiple inflammatory mechanisms causing cardiac remodeling, dysfunction and chronic failure. Therapeutics in trials targeting the immune response in heart failure and its effects did not result in evident benefits regarding clinical endpoints and mortality. This review elaborates pathways of immune cytokines in pathogenesis and worsening of heart failure in clinical and cellular settings. Besides the well-known mechanisms of immune activation and inflammation in atherosclerosis causing ischemic cardiomyopathy or myocarditis, attention is focused on other mechanisms leading to heart failure such as transthyretin (TTR) amyloidosis or heart failure with preserved ejection fraction. The knowledge of the pathogenesis in heart failure and amyloidosis on a molecular and cellular level might help to highlight new disease defining biomarkers and to lead the way to new therapeutic targets.

IntroductionDespite optimal medical therapy (OMT), patients with HFrEF may remain symptomatic leading to increased hospitalisation or death. The European Society of Cardiology guidelines for heart failure recommend cardiac resynchronisation therapy (CRT) and/or implantable cardiac defibrillators (ICD) in patients with persisting left ventricular function impairment and/or are symptomatic despite optimal medical therapy. We hypothesise that during complex device implant, right heart catheterization is feasible and could identify patients at higher risk of heart failure decompensation.Methods17 patients with HFrEF on OMT (mean age 62+8 years, 12% female and 29% non-ischaemic cardiomyopathy), admitted electively for an ICD or CRT implantation at Morriston Cardiac Centre, Swansea, UK underwent right heart pressure measurement during the procedure. The patient was consented for ICD or CRT implant and additionally for a right heart catheterisation during device implantation.Axillary, cephalic or subclavian vein access was gained and the right ventricular (RV) lead was implanted and fixed. A SafeSheathTM (Pressure Products) was inserted. A balloon catheter was then inserted and used to measure mean right atrial (mRAP), mean RV, mean pulmonary artery pressure (mPAP) and mean pulmonary capillary wedge pressure (mPCWP). The balloon catheter was then removed. The left ventricular lead and atrial lead were then implanted and fixed. The ICD/CRT device was then implanted and the wound closed with absorbable sutures.ResultsAll but 2 patients were on OMT due to brady-arrhythmia. The mRAP was 5+3 mmHg, mRVP was 27+11 mmHg, mPAP was 17+ 8 mmHg and mPCWP was 10+7 mmHg. 13 (76%) patients had normal mPAP (<20 mmHg), 1 (5.8%) had mPAP between 20–25 mmHg and 3 (17.6%) patients had elevated mPAP >25 mmHg. Right heart pressure measuremments did not significantly prolong procedure time with a mean procedure length of 101+35 minutes for CRT implantation and 64+42 minutes for ICD. Of the 3 patients with mPAP >25 mmHg, 2 had an increase in diuretic therapy as a result, which was well tolerated. There were no peri-procedural or post-procedural complications. One patient had a device related infection, which necessitate device extraction and subsequent contralateral re-implantation.ConclusionsElevated pressures during ICD/CRT implantation may identify patients at a higher risk of heart failure related events and prompt closer follow up.Abstract 172 Table 1Baseline characteristics of patients undergoing complex device implant and right heart pressure measurements Characteristic Age62±8Percentage female12%Non-ischaemic aetiology30%Atrial Fibrillation29%Type 2 diabetes35%NYHA class III-IV12%On OMT 88%Additional diuretic therapy41%CRT implantation88%Abstract 172 Table 2Characteristics of patients undergoing device implantation and right heart pressure measurements, grouped by mean PA pressure Characteristic Group 1 (mPAP <20) n=13 Group 2 (mPAP 21–24) n=1 Group 2 (mPAP >25) n=3 Age (yrs) 68 62 68 Percentage female 8% 0% 33% Non-ischaemic aetiology 38% 0% 33% Atrial Fibrillation 24% 0% 33% Type 2 diabetes 39% 0% 33% NYHA class III-IV 15% 0% 0% On OMT 85% 0% 67% Additional diuretic therapy 31% 100% 67% CRT-D 61% 0% 100% CRT-P 23% 0% 0% ICD 15% 100% 0% Conflict of InterestNil