Left Ventricular Ejection Fraction Subgroups Research Articles

Sodium-glucose co-transporter 2 inhibitors in acute heart failure: real-world prescription trends and outcomes analysis.

Sodium-glucose co-transporter 2 (SGLT2) inhibitors have shown potential therapeutic benefits in heart failure (HF). However, data on their real-world usage and benefits in acute decompensated heart failure (ADHF) are limited. We conducted a post hoc analysis of real-world data from 1108 patients with ADHF admitted to Nihon University Itabashi Hospital (Tokyo, Japan) between 2018 and 2022. Patients were divided into two groups based on the prescription of SGLT2 inhibitors during hospitalization: an SGLT2 inhibitor group (SGLT2i group) (n=289) and a non-SGLT2i group (n=819). The primary endpoints were death and rehospitalization for HF after discharge. The median age was 76 [interquartile range (IQR): 66, 83] years, and 732 patients (66%) were male. Data showed an increasing trend in the prescription of SGLT2 inhibitors since 2021. During a median follow-up period of 366days (IQR: 116, 614), 458 (41.3%) patients reached the primary endpoint. The Kaplan-Meier analysis showed that the SGLT2i group had a significantly lower rate of composite events than the non-SGLT2i group, both overall (log-rank test, P<0.001) and in the following left ventricular ejection fraction (LVEF) subgroups: HF with reduced ejection fraction (EF) (n=413), HF with mildly reduced EF (n=226), and HF with preserved EF (n=466) (log-rank test; P=0.044, P=0.013, and P=0.001, respectively). Furthermore, patients starting SGLT2 inhibitors during hospitalization had a significantly lower rate of composite events than those not using SGLT2 inhibitors (log-rank test, P<0.001). This association was also significant in the LVEF subgroups (P=0.005, P=0.032, and P=0.004, respectively). The prescription and initiation of SGLT2 inhibitors during hospitalization are associated with improved post-discharge outcomes in patients with ADHF, irrespective of LVEF.

Dobutamine stress echocardiography in low-gradient aortic stenosis

Abstract Background Dobutamine stress echocardiography (DSE) is recommended to distinguish between true-severe and pseudo-severe aortic stenosis (AS) in patients with low flow low-gradients and left ventricular ejection fraction (LVEF) &amp;lt;50%. However, DSE has mostly been tested in the setting of LVEF&amp;lt;35%. Purpose The purpose of this study was to examine the diagnostic accuracy of DSE according to aortic valve calcification (AVC) score, in patents with low-flow, low-gradient AS across a wide range of LVEF. Methods Patients with aortic mean gradient &amp;lt;40 mmHg, aortic valve area (AVA) &amp;lt;1.0 cm2, and stroke volume index (SVi) ≤35 mL/m2 undergoing DSE were identified from three prospectively collected patient cohorts, and stratified according to LVEF; &amp;lt;35%, 35-50% and &amp;gt;50%. Severe AS was defined as AVC score ≥2000 AU among men, and ≥1200 AU for women. Recommendation for severe AS according to DSE, are an AVA &amp;lt;1.0 cm2 combined with an aortic mean gradient ≥40 mmHg or peak velocity ≥4 m/s. Receiver operating characteristic curves for DSE-derived AVA, mean gradient and Vmax were used to identify optimal cut-off points for each LVEF subgroup. Results Of the 221 patients included in the study, 78 (35%) presented with LVEF &amp;lt;35%, 67 (30%) with LVEF 35-50%, and 76 (34%) with LVEF &amp;gt;50%. Baseline characteristics are presented in the table. Based on AVC, severe AS was present in 102 (46%) of patients. Using recommended thresholds for severe AS for AVC and DSE, led to a sensitivity of 49%, a specificity of 84% and an accuracy of 67% for DSE for all patients with LVEF &amp;lt;50%, but with significant heterogeneity between groups figure. AVA performed rather uniformly across LVEF subgroups; (AUC =0.68 vs 0.62 vs 0.54, p=0.36) LVEF&amp;lt;35%, LVEF 35-50%, LVEF&amp;gt;50% respectively and displayed a rather uniform optimal cut-off (1.0 cm2 vs 0.9 cm2 vs 0.8 cm2). However, mean gradient and Vmax during DSE, both showed significantly diagnostic heterogeneity across LVEF groups (AUC= 0.90 vs 0.67 vs 0.65, p=&amp;lt;0.001 and AUC= 0.90 vs 0.66 vs 0.60, p=&amp;lt;0.001) with different optimal thresholds (30 mmHg &amp; 3.8 m/s, 45 mmHg &amp; 4.3 m/s and 37mmHg &amp; 4 m/s, LVEF&amp;lt;35%, LVEF 35-50%, LVEF&amp;gt;50%, respectively). Conclusion Our study shows, that the association between DSE gradients and AS severity assessed by AVC demonstrates important heterogeneity depending on LVEF. While DSE had the highest accuracy in patients with LVEF&amp;lt;35% both patients with LVEF 35-50%, and patients with LVEF&amp;gt;50% showed significantly less concordance between DSE and AVC.

Abstract 17855: Improvement of Mitral Valve Regurgitation Severity Following Catheter Ablation for Atrial Fibrillation

Background: The presence of concomitant mitral valve regurgitation (MR) in patients with atrial fibrillation (AF) is well known, yet the degree of MR improvement after catheter ablation is not well studied. We investigated the effect of catheter ablation on the degree of MR in patients with baseline ≥moderate MR and AF. Methods: We retrospectively reviewed charts of AF catheter ablation patients at Montefiore Medical Center (2018-2019). Patients with prior or subsequent mitral valve surgeries were excluded. Degree of MR, assessed through echocardiograms, was compared at baseline and follow-up. Early follow-up was defined as 6 months post-ablation. Patients were stratified by left atrial size and left ventricular ejection fraction (LVEF) to assess the influence of these parameters on MR severity after ablation. Results: A total of 202 patients were included in our analysis with an average age of 64 years. At baseline there were 149 patients (74%) with &lt;moderate MR and 44 patients with ≥moderate MR (22%). There was a statistically significant reduction in the number of patients with ≥moderate MR following ablation both at early and late follow-up (p&amp;lt;0.0001, Figure 1). Our results remained statistically significant after stratification by LVEF (&lt;40% vs ≥ 40%) and LA dimension (&lt;4.5cm vs ≥ 4.5cm) (p&amp;lt;0.001, Figure 2). Conclusions: Catheter ablation of AF improved the degree of MR severity in patients with baseline ≥moderate MR and AF. Our findings were preserved across stratification by left atrial size and LVEF subgroups. Further investigation is necessary to validate our findings.

Pharmacological Treatments in Heart Failure With Mildly Reduced and Preserved Ejection Fraction: Systematic Review and Network Meta-Analysis

BackgroundMedical treatment for heart failure with preserved ejection (HFpEF) and heart failure with mildly reduced ejection fraction (HFmrEF) has weaker evidence compared with reduced ejection fraction, despite recent trials with an angiotensin receptor neprilysin inhibitor (ARNI) and sodium glucose co-transporter 2 inhibitors (SGLT2is). ObjectivesThe authors aimed to estimate the aggregate therapeutic benefit of drugs for HFmrEF and HFpEF. MethodsThe authors performed a systematic review of MEDLINE, CENTRAL, and Web of Science for randomized trials including patients with heart failure (HF) and left ventricular ejection fraction (LVEF) >40%, treated with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (analyzed together as renin-angiotensin system inhibitors [RASi]), beta-blockers (BBs), mineralocorticoid receptor antagonists (MRAs), digoxin, ARNI, and SGLT2i. An additive component network meta-analysis was performed. The primary outcome was a composite of cardiovascular (CV) death and first hospitalization for heart failure (HHF); secondary outcomes were CV death, total HHF, and all-cause mortality. ResultsThe authors identified 13 studies with a total of 29,875 patients and a mean LVEF of 56.3% ± 8.7%. ARNI, MRA, and SGLT2i separately, but not RASi, BB, or digoxin, reduced the primary composite outcome compared with placebo. The combination of ARNI, BB, MRA, and SGLT2i was the most effective (HR: 0.47 [95% CI: 0.31-0.70]); this was largely explained by the triple combination of ARNI, MRA, and SGLT2i (HR: 0.56 [95% CI 0.43-0.71]). Results were similar for CV death (HR: 0.63 [95% CI 0.43-0.91] for ARNI, MRA, and SGLT2i) or total HHF (HR: 0.49 [95% CI 0.33-0.71] for ARNI, MRA, and SGLT2i) alone. In a subgroup analysis, only SGLT2i had a consistent benefit among all LVEF subgroups, whereas the triple combination had the greatest benefit in HFmrEF, robust benefit in patients with LVEF 50% to 59%, and a statistically marginal benefit in patients with LVEF ≥60%. ConclusionsIn patients with HF and LVEF>40%, the quadruple combination of ARNI, BB, MRA, and SGLT2i provides the largest reduction in the risk of CV death and HHF; driven by the robust effect of the triple combination of ARNI, MRA, and SGLT2i. The benefit was more pronounced in HFmrEF patients.

Remote patient management of heart failure across the ejection fraction spectrum: a pre-specified analysis of the TIM-HF2 trial.

The benefit of non-invasive remote patient management (RPM) for patients with heart failure (HF) has been demonstrated. We evaluated the effect of left ventricular ejection fraction (LVEF) on treatment outcomes in the TIM-HF2 (Telemedical Interventional Management in Heart Failure II; NCT01878630) randomized trial. TIM-HF2 was a prospective, randomized, multicentre trial investigating the effect of a structured RPM intervention versus usual care in patients who had been hospitalized for HF within 12 months before randomization. The primary endpoint was the percentage of days lost due to all-cause death or unplanned cardiovascular hospitalization. Key secondary endpoints were all-cause and cardiovascular mortality. Outcomes were assessed by LVEF in guideline-defined subgroups of ≤40% (HF with reduced EF [HFrEF]), 41-49% (HF with mildly reduced EF [HFmrEF]), and ≥50% (HF with preserved EF [HFpEF]). Out of 1538 participants, 818 (53%) had HFrEF, 224 (15%) had HFmrEF, and 496 (32%) had HFpEF. Within each LVEF subgroup, the primary endpoint was lower in the treatment group, i.e. the incidence rate ratio [IRR] remained below 1.0. Comparing intervention and control group, the percentage of days lost was 5.4% versus 7.6% for HFrEF (IRR 0.72, 95% confidence interval [CI] 0.54-0.97), 3.3% versus 5.9% for HFmrEF (IRR 0.85, 95% CI 0.48-1.50) and 4.7% versus 5.4% for HFpEF (IRR 0.93, 95% CI 0.64-1.36). No interaction between LVEF and the randomized group became apparent. All-cause and cardiovascular mortality were also reduced by RPM in each subgroup with hazard ratios <1.0 across the LVEF spectrum for both endpoints. In the clinical set-up deployed in the TIM-HF2 trial, RPM appeared effective irrespective of the LVEF-based HF phenotype.

The influence of comorbidities on the prognosis after an acute heart failure decompensation and differences according to ejection fraction: Results from the EAHFE and RICA registries

ObjectiveThe role of comorbidities in heart failure (HF) outcome has been previously investigated, although mostly individually. We investigated the individual effect of 13 comorbidities on HF prognosis and looked for differences according to left-ventricular ejection fraction (LVEF), classified as reduced (HFrEF), mildly-reduced (HFmrEF) and preserved (HFpEF). MethodsWe included patients from the EAHFE and RICA registries and analysed the following comorbidities: hypertension, dyslipidaemia, diabetes mellitus (DM), atrial fibrillation (AF), coronary artery disease (CAD), chronic kidney disease (CKD), chronic obstructive pulmonary disease (COPD), heart valve disease (HVD), cerebrovascular disease (CVD), neoplasia, peripheral artery disease (PAD), dementia and liver cirrhosis (LC). Association of each comorbidity with all-cause mortality was assessed by an adjusted Cox regression analysis that included the 13 comorbidities, age, sex, Barthel index, New York Heart Association functional class and LVEF and expressed as adjusted Hazard Ratios (HR) with 95% confidence intervals (95%CI). ResultsWe analysed 8,336 patients (82 years-old; 53% women; 66% with HFpEF). Mean follow-up was 1.0 years. Respect to HFrEF, mortality was lower in HFmrEF (HR:0.74;0.64-0.86) and HFpEF (HR:0.75;0.68-0.84). Considering patients all together, eight comorbidities were associated with mortality: LC (HR:1.85;1.42-2.42), HVD (HR:1.63;1.48-1.80), CKD (HR:1.39;1.28-1.52), PAD (HR:1.37;1.21-1.54), neoplasia (HR:1.29;1.15-1.44), DM (HR:1.26;1.15-1.37), dementia (HR:1.17;1.01-1.36) and COPD (HR:1.17;1.06-1.29). Associations were similar in the three LVEF subgroups, with LC, HVD, CKD and DM remaining significant in the three subgroups. ConclusionHF comorbidities are associated differently with mortality, LC being the most associated with mortality. For some comorbidities, this association can be significantly different according to the LVEF.

Epidemiology and Outcomes of Aortic Stenosis in Acute Decompensated Heart Failure: The ARIC Study.

Few studies characterize the epidemiology and outcomes of aortic stenosis (AS) in acute decompensated heart failure (ADHF). This study investigates the significance of AS in contemporary patients who have experienced an ADHF hospitalization. The ARIC study (Atherosclerosis Risk in Communities) surveilled ADHF hospitalizations for residents ≥55 years of age in 4 US communities. ADHF cases were stratified by left ventricular ejection fraction (LVEF). Demographic differences in AS burden and the association of varying AS severities with mortality were estimated using multivariable logistic regression. From 2005 through 2014, there were 3597 (weighted n=16 692) ADHF hospitalizations of which 48.6% had an LVEF <50% and 51.4% an LVEF ≥50%. AS prevalence was 12.1% and 18.7% in those with an LVEF <50% and ≥50%, respectively. AS was less likely in Black than White patients regardless of LVEF: LVEF <50% (odds ratio [OR], 0.34 [95% CI, 0.28-0.42]); LVEF ≥50% (OR, 0.51 [95% CI, 0.44-0.59]). Higher AS severity was independently associated with 1-year mortality in both LVEF subgroups: LVEF <50% (OR, 1.16 [95% CI, 1.04-1.28]); LVEF ≥50% (OR, 1.40 [95% CI, 1.28-1.54]). Sensitivity analyses excluding severe AS patients detected that mild/moderate AS was independently associated with 1-year mortality in both LVEF subgroups: LVEF <50% (OR, 1.23 [95% CI, 1.02-1.47]); LVEF ≥50% (OR, 1.31 [95% CI, 1.14-1.51]). Among patients who have experienced an ADHF hospitalization, AS is prevalent and portends poor mortality outcomes. Notably, mild/moderate AS is independently associated with 1-year mortality in this high-risk population.

PARADISE-MI – event rates and treatment effect of sacubitril/valsartan v ramipril by the presence or absence of transient pulmonary congestion and/or LVEF less or greater than 40

Abstract Background/Introduction Sacubitril/valsartan was compared to ramipril in patients with acute myocardial infarction in the PARADISE-MI trial. In the whole trial population sacubitril/valsartan did not reduce the composite primary outcome of CV death or incident heart failure compared to ramipril. Whether or not event rates and/or treatment effects vary in patients with different baseline characteristics is unknown. Purpose To investigate a) event rates b) the treatment effect of sacubitril/valsartan compared to ramipril and c) safety by the presence or absence of transient pulmonary congestion and/or left ventricular ejection fraction (LVEF) ≤40%. Methods PARADISE-MI was a double-blind, randomised clinical trial that compared sacubitril/valsartan to ramipril in 5661 patients with an acute myocardial infarction with either LVEF ≤40% and/or transient pulmonary congestion. 3 groups were investigated: 1) LVEF ≤40% with pulmonary congestion (n=2012) and 2) LVEF ≤40% without pulmonary congestion (n=2596) and 3) LVEF not ≤40% with pulmonary congestion (n=1044). Results Patients with pulmonary congestion (with and without LVEF ≤40%) were more likely to have had a prior MI, prior CABG or PCI, had more atrial fibrillation and were more often treated with mineralocorticoid receptor antagonists and diuretics than patients with no pulmonary congestion and LVEF ≤40%. Patients with LVEF ≤40% and pulmonary congestion had more than twice the rate of the primary composite outcome compared to those with LVEF ≤40% without pulmonary congestion: 10.2 (95% CI 9.2–11.3) vs. 4.8 (4.3–5.5) events per 100 patient-years, respectively). Patients with pulmonary congestion and LVEF not ≤40% had an intermediate event rate (6.6, 5.5–7.9, events per 100 patient-years). A similar pattern of event rates was seen for the components of the primary outcome and for all secondary outcomes whether Clinical Events Committee or investigator-reported events were analysed. The treatment effect of sacubitril/ valsartan versus ramipril did not vary between the 3 congestion/ LVEF subgroups. The safety of sacubitril/valsartan compared to ramipril did not vary between congestion/LVEF subgroups. Conclusion Patients with pulmonary congestion with or without LVEF ≤40% had higher rates of primary and all secondary outcomes than those without pulmonary congestion and LVEF ≤40%. The treatment effect, and safety, of sacubitril/valsartan compared to ramipril was consistent in patients with or without pulmonary congestion and with or without LVEF ≤40%. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Novartis

Impact of left ventricular ejection fraction on 10-year mortality after percutaneous coronary intervention or coronary artery bypass grafting

Abstract Backgrounds The impact on vital prognosis at very long-term of percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) in patients with reduced ejection fraction (EF) remains to be elucidated. Objective To investigate the impact of left ventricular ejection fraction (LVEF) on 10-year mortality after PCI and CABG in the SYNTAX trial. Methods In the SYNTAXES study, 1,800 randomized patients were categorized into three groups according to the current guidelines; (1) reduced EF (rEF; LVEF ≤40%), (2) mildly reduced EF (mrEF; LVEF 41–49%), (3) preserved EF (pEF; LVEF ≥50%). The primary endpoint was 10-year all-cause mortality. Event rate up to 10 years was estimated according to the Kaplan-Meier method, and the log-rank test was performed to examine the differences among LVEF subgroups. The SYNTAX score 2020 (SS-2020) was compared between the patients with reduced (LVEF &amp;lt;50%) and preserved EF (LVEF ≥50%) in order to better refine their respective personalized vital prognosis and assess in cross-validation the value of the risk score. Results The population was stratified as rEF (n=168), mrEF (n=179), and pEF (n=1453). Ten-year all-cause mortality were 44.0% vs. 31.8% vs. 22.6% (P&amp;lt;0.001), in patients with rEF, mrEF and pEF, respectively. The significant interaction was not identified between LVEF classification and treatment (P interaction = 0.183). In patients with rEF, there was a tendency toward higher mortality in PCI group than CABG (52.9% vs 39.6%, P=0.054), and no significant differences in patients with mrEF (36.0% vs. 28.6%, P=0.273) and pEF (23.9% vs. 22.2%, P=0.275). According to the SS-2020, PCI was a relatively safe modality of revascularization in 37.8% of the patients with reduced EF (LVEF &amp;lt;50%). In the population with preserved EF (LVEF ≥50%), the proportion of patients eligible to PCI with predicted equipoise in mortality with CABG was 57.5%. Conclusion LVEF could an important factor for determining the revascularization treatment in patients presenting with complex coronary artery disease. Calculation of individualized 10-year prognosis using the SS-2020 may be a viable option in decision-making. Funding Acknowledgement Type of funding sources: None.

Heart failure hospitalizations and diuretic use before and after first-time pulmonary vein isolation ablation for atrial fibrillation among patients with heart failure

Abstract Background Small randomized clinical trials have found that patients with heart failure (HF) and atrial fibrillation (AF) randomized to an ablation strategy for AF experienced improved cardiovascular outcomes. We examined the relation in routine clinical practice. Purpose We aimed to assess if first-time pulmonary vein isolation ablation (PVI) for AF among patients with HF was associated with decrease in HF hospital admissions rates and furosemide dosage in the year after PVI compared with the year before. Methods We identified patients with HF and available left ventricular ejection fraction (LVEF) treated with a first-time PVI using the Danish Ablation Registry, and alive at 1-year follow-up. Patient comorbidities and concomitant pharmacotherapy (including furosemide dosage and HF hospital admissions) were identified utilizing Danish nationwide registries. For inclusion, patients were required to have been diagnosed with HF in an in- or outpatient setting &amp;lt;10 years of first-time PVI or have a LVEF at the time of PVI ≤45%. Patients were grouped according to LVEF at time of PVI: ≤35%, 36–45%, and &amp;gt;45%. For comparison of HF hospital admission and furosemide usage before and after PVI, McNemars test were used. Wilcox signed-rank test were used to test difference in furosemide dosage before and after PVI. Results We identified 668/3450 patients with HF treated with first-time PVI for AF between 2010–2017 (median age 62 years [Q1,Q3=56,69 years], 81% male, and median LVEF 45% [Q1,Q3=40,60%]). Of these, 13 patients (2%) died during one-year follow-up. Overall, 36% of patients with HF had one or more HF hospital admissions the year before PVI compared with 7% in the year after PVI (p&amp;lt;0.0001) (Figure 1). Patients with LVEF ≤35% had the highest proportion of HF hospital admissions the year before PVI (53%) and was reduced more than 4-fold (13%) in the year after first-time PVI, with consistent findings in all LVEF groups (Figure 1). At the time of PVI, 36% of patients with HF were treated with furosemide compared with 30% in the year after PVI (p&amp;lt;0.0001) (Figure 2). Moreover, we identified significant reductions in furosemide dose in the year after PVI compared with the year before (median dose 60 mg [Q1,Q3=30,80 mg] and 20 mg [Q1,Q3=0,60 mg], respectively, p=0.001). Here, reductions in furosemide requirements were consistent across LVEF subgroups. Conclusion Patients with HF treated with a first-time PVI strategy for AF had a 5-fold decrease in HF hospital admissions in the following year compared with the year before PVI. Among patients treated with furosemide at time of PVI, significant reductions in dose one year after PVI was identified but also significant reductions in proportion of patients requiring any furosemide at all. Funding Acknowledgement Type of funding sources: None.

Impact of small-airway disease on exercise intolerance and long-term outcomes in patients with heart failure and reduced or preserved ejection fraction

Abstract Introduction Exercise intolerance in patients with heart failure (HF) is a strong indicator of a poor prognosis. As the respiratory impairment in HF patients, the small airway is reportedly more susceptible than central airways, which results in increased airway resistance and may cause poor outcomes. However, the impact of small-airway disease (SAD) on exercise intolerance and prognosis in patients with HF is still unclear. Purpose We investigated the associations between SAD and exercise intolerance in patients with HF, and the clinical significance of SAD for long-term clinical events with a reduced or preserved ejection fraction. Methods We reviewed 1015 patients with HF (mean age, 66.9±14.6 years; male, 64.5%) admitted for medical treatment. Patients with a prior history of chronic respiratory disease or an obstructive lung pattern – defined as the forced expiratory volume (%) in 1 s relative to &amp;lt;70% forced vital capacity using spirometry – were excluded. Characteristics including HF aetiology, comorbidities conditions, medications, blood parameters, and echocardiographic variables were obtained from clinical records. All patients underwent spirometry at hospital discharge, and SAD was defined as the maximum mid-expiratory flow (%) relative to a &amp;lt;60% predicted value. At hospital discharge, we measured 6-min walk distance (6MWD), and &amp;lt;300 m was considered as exercise intolerance. The primary endpoint was a composite clinical event of all-cause death and/or unplanned readmission for HF. Multivariate logistic regression analysis was used to assess the association between SAD and exercise intolerance. The multivariate Cox proportional hazard model was used to clarify whether SAD was an independent predictor for the incidence of clinical events. We also performed subgroup analyses in each multivariate analysis based on a left ventricular ejection fraction (LVEF) of 40%. Result SAD was observed in 479 (47.2%) patients. LVEF subgroups included 458 (45.1%) and 518 (51.0%) patients with LVEF &amp;lt;40% and ≥40%, respectively. After adjusting for clinical characteristics, SAD was independently associated with 6MWD &amp;lt;300 m (Figure 1). Moreover, this association was consistently observed in the LVEF &amp;lt;40% and ≥40% (Figure 1). During the median follow-up period of 1.5 years, all-cause death/readmission occurred in 431 patients (42.5%), and the incidence rate was 17.5/100 person-years. In the multivariate Cox proportional hazard model, SAD was independently associated with lower event-free survival rates in all patients and the LVEF &amp;lt;40% subgroup, but not LVEF ≥40% subgroup (Figure 2A, B, and C, respectively). Conclusion This study is the first to reveal that SAD is associated with exercise intolerance in patients with HF regardless of LVEF. Moreover, SAD may have a predictive significance for long-term outcomes in patients with HF and subgroups with reduced, but not preserved ejection fraction. Funding Acknowledgement Type of funding sources: None.

THE EFFECT OF BETA BLOCKAGE IN PATIENTS FOLLOWING ACUTE CORONARY SYNDROME - STRATIFIED ACCORDING TO LEFT VENTRICULAR EJECTION FRACTION.

THE EFFECT OF BETA BLOCKAGE IN PATIENTS FOLLOWING ACUTE CORONARY SYNDROME - STRATIFIED ACCORDING TO LEFT VENTRICULAR EJECTION FRACTION.

Promise of sodium-glucose co-transporter-2 inhibitors in heart failure with mildly reduced ejection fraction.

Heart failure with mildly reduced ejection fraction (HFmrEF) is associated with comparable poor outcomes as other subtypes of heart failure and remains a medical unmet need due to the paucity of effective therapies. According to large cardiovascular (CV) outcome trials in patients with heart failure, sodium–glucose co‐transporter‐2 inhibitors (SGLT2is) reduce CV mortality and hospitalizations for heart failure in patients with heart failure across the spectrum of left ventricular ejection fraction (LVEF). There has been a lack of dedicated trials in HFmrEF. However, several large outcome trials in heart failure that enrolled patients with HFmrEF could provide a hint on the role of SGLT2is in this subgroup. This review focuses on CV effects of three major SGLT2is—dapagliflozin, empagliflozin, and sotagliflozin—in patients with HFmrEF. A narrative review of trials investigating the efficacy of each medication in treating heart failure with LVEF > 40% is provided with a focus on their LVEF subgroup analyses. The purpose of this review is to discuss the current state of evidence regarding the potential of SGLT2is in HFmrEF management. Current limited evidence suggests that SGLT2is might be a favourable treatment modality for patients with HFmrEF to reduce hospitalization for heart failure and CV mortality. This conclusion needs to be further supported by clear HFmrEF subgroup analysis of the existing trials. Further outcome trials involving sufficient patients with different subtypes of HFmrEF are needed to confirm and assess CV benefits of SGLT2is in HFmrEF. Possible mechanisms by which SGLT2is exert their cardioprotective effect are also described briefly.

Abstract 10993: Prognostic Value of Low T 3 Syndrome in Patients with Acute Decompensated Heart Failure in Osaka Prefectural Acute Heart Failure Registry (OPAR)

Backgrounds: It is widely recognized that thyroid dysfunction is a potential cause of heart failure (HF). In HF, one of the alterations of thyroid functions is referred to as low T 3 syndrome marked by a reduction in serum free triiodothyronine (T 3 ) with normal levels of thyroid-stimulating hormone (TSH). However, there is little information available about the association between low T 3 syndrome and future cardiac events in patients with acute decompensated heart failure (ADHF), relating to left ventricular ejection fraction (LVEF). Methods and Results: We studied 565 patients admitted for ADHF with survival discharge in our prospective cohort study. Laboratory data including free T 3 , thyroxine and TSH were obtained at discharge. Among the patients with euthyroid (0.35 μU/mL &lt;TSH &lt;4.94 μU/mL, n=438), there was 62 patients who were diagnoses as low T 3 syndrome (free T 3 ≦1.68 pg/mL). The primary end point of this study was all-cause death (ACD). During a mean follow up period of 2.9±1.4 years, 121 patients died. Study subjects were stratified into two LVEF subgroup as follows; 239 patients had LVEF&lt;50% (HFrEF), and 199 patients had LVEF≧50% (HFpEF). While 68 HFrEF parients died, 53 HFpEF patients died. Kaplan-Meier curve analysis revealed that patients with the low free T 3 group had the greater risk of ACD than those with the normal free T 3 group in both LVEF subgroup (log-rank p=0.0233 in HFrEF and p=0.0265 in HFpEF). Multivariate Cox analysis showed that free T 3 was significantly associated with ACD after multivariable adjustment for major confounders, such as age, sex, systolic blood pressure and plasma brain natriuretic peptide level in both LVEF subgroup (p=0.0039 in HFrEF, p=0.0487 in HFpEF). Conclusion: Low T 3 syndrome was significantly associated with poor outcome in ADHF patients with both HFrEF and HFpEF.

Abstract 10141: Outcomes in Elderly Patients with Hospitalized Heart Failure Stratified by Left Ventricular Ejection Fraction

Introduction: The prevalence of heart failure (HF) has increased markedly with age. Given the influence of age and left ventricular ejection fraction (LVEF) on the mortality in HF, the assessment of clinical outcomes in elderly patients stratified LVEF categories may provide better care decisions in clinical settings. Methods: Between 2006 and 2017, 3558 consecutive patients enrolled in a prospective multicenter registry in Japan (the West Tokyo Heart Failure registry) were analyzed. We divided the patients into three age groups: &lt;65 years (younger), 75-84 years (elderly), and ≥85 years (very-elderly) by each LVEF subgroup (HF with preserved ejection fraction [HFpEF, LVEF ≥50%] or non-HFpEF [LVEF &lt;50%]). The primary endpoint was all-cause mortality after discharge. We performed a multivariate cox proportional hazards analysis to identify the risk factors for all-cause death using several covariates. Results: Overall, 1505 HFpEF (younger: n=182, elderly: n=894, very-elderly: n=429) and 2053 non-HFpEF (younger: n=575, elderly: n=1159, very-elderly: n=319) were included in this study. During the median follow-up period of 2.0 years, the incidence of all-cause death was almost similar in both HFpEF and non-HFpEF groups (19.2% vs. 20.3%, p=0.60 for log-rank test). The mortality increased substantially with increasing age categories, and also differed by LVEF categories (Figure). After multivariable adjustments, age (per 1-year increase) and LVEF (per 1% decrease) were the significant predictors of all-cause death (age: hazard ratio [HR] 1.04, 95% confidence interval [CI] 1.03-1.05, p&lt;0.001; LVEF: HR 1.01, 95% CI 1.01-1.02, p&lt;0.01). Conclusions: In contemporary Japanese clinical practice with aging, age was closely associated with higher risks for all-cause death, and the mortality was stratified by LVEF categories.

Myocardial Work by Speckle Tracking Echocardiography Accurately Assesses Left Ventricular Function of Coronary Artery Disease Patients.

Objective: Myocardial work (MW) is a novel non-invasive method that uses speckle tracking echocardiography (STE) to assess left ventricular (LV) function. MW incorporates the global longitudinal strain and afterload conditions. Here we aimed to use MW to assess the LV function of patients with coronary artery disease (CAD) with or without heart failure (HF).Methods: We enrolled a total of 150 individuals (50 each) with CAD and a normal LV ejection fraction (LVEF), CAD with HF, and healthy controls. Patients were divided into the hypertension (HTN) and normal blood pressure (no HTN) subgroups. MW was determined from the pressure-strain loop using STE. The relationships between MW indices and conventional echocardiographic parameters were evaluated, and the MW indices were compared among groups.Results: Univariate and multivariate analyses showed that MW indices were strongly correlated with LVEF. The global work index (GWI) was increased in the CAD with normal LVEF subgroup with HTN vs. controls (1,922.3 ± 393.1 vs. 1,639.7 ± 204.6 mmHg%, p < 0.05) and decreased in CAD patients with HF (no HTN: 940.9 ± 380.6 vs. 1,639.7 ± 204.6 mmHg%, p < 0.05; HTN: 857.3 ± 369.3 vs. 1,639.7 ± 204.6 mmHg%, p < 0.05). Global waste work was increased in all CAD subgroups vs. controls. Global constructive work had the same tendency as GWI in patients with CAD. Global MW efficiency was decreased in all patients with CAD.Conclusion: MW using STE accurately quantifies LV function in patients with CAD. It offers additional information about LV function with respect to disease progression, particularly in CAD patients with a normal LVEF.

Trajectories of Left Ventricular Ejection Fraction After Acute Decompensation for Systolic Heart Failure: Concomitant Echocardiographic and Systemic Changes, Predictors, and Impact on Clinical Outcomes.

BackgroundProspective longitudinal follow‐up of left ventricular ejection fraction (LVEF) trajectories after acute cardiac decompensation of heart failure is lacking. We investigated changes in LVEF and covariates at 6‐months' follow‐up in patients with a predischarge LVEF ≤40%, and determined predictors and prognostic implications of LVEF changes through 18‐months' follow‐up.Methods and ResultsInterdisciplinary Network Heart Failure program participants (n=633) were categorized into subgroups based on LVEF at 6‐months' follow‐up: normalized LVEF (>50%; heart failure with normalized ejection fraction, n=147); midrange LVEF (41%–50%; heart failure with midrange ejection fraction, n=195), or persistently reduced LVEF (≤40%; heart failure with persistently reduced LVEF , n=291). All received guideline‐directed medical therapies. At 6‐months' follow‐up, compared with patients with heart failure with persistently reduced LVEF, heart failure with normalized LVEF or heart failure with midrange LVEF subgroups showed greater reductions in LV end‐diastolic/end‐systolic diameters (both P<0.001), and left atrial systolic diameter (P=0.002), more increased septal/posterior end‐diastolic wall‐thickness (both P<0.001), and significantly greater improvement in diastolic function, biomarkers, symptoms, and health status. Heart failure duration <1 year, female sex, higher predischarge blood pressure, and baseline LVEF were independent predictors of LVEF improvement. Mortality and event‐free survival rates were lower in patients with heart failure with normalized LVEF (P=0.002). Overall, LVEF increased further at 18‐months' follow‐up (P<0.001), while LV end‐diastolic diameter decreased (P=0.048). However, LVEF worsened (P=0.002) and LV end‐diastolic diameter increased (P=0.047) in patients with heart failure with normalized LVEF hospitalized between 6‐months' follow‐up and 18‐months' follow‐up.ConclusionsSix‐month survivors of acute cardiac decompensation for systolic heart failure showed variable LVEF trajectories, with >50% showing improvements by ≥1 LVEF category. LVEF changes correlated with various parameters, suggesting multilevel reverse remodeling, were predictable from several baseline characteristics, and were associated with clinical outcomes at 18‐months' follow‐up. Repeat hospitalizations were associated with attenuation of reverse remodeling.RegistrationURL: https://www.controlled‐trials.com; Unique identifier: ISRCTN23325295.

The Interrelationship between Ventilatory Inefficiency and Left Ventricular Ejection Fraction in Terms of Cardiovascular Outcomes in Heart Failure Outpatients.

The relationship between left ventricular ejection fraction (LVEF) and cardiovascular (CV) outcome is documented in patients with low LVEF. Ventilatory inefficiency is an important prognostic predictor. We hypothesized that the presence of ventilatory inefficiency influences the prognostic predictability of LVEF in heart failure (HF) outpatients. In total, 169 HF outpatients underwent the cardiopulmonary exercise test (CPET) and were followed up for a median of 9.25 years. Subjects were divided into five groups of similar size according to baseline LVEF (≤39%, 40–58%, 59–68%, 69–74%, and ≥75%). The primary endpoints were CV mortality and first HF hospitalization. The Cox proportional hazard model was used for simple and multiple regression analyses to evaluate the interrelationship between LVEF and ventilatory inefficiency (ventilatory equivalent for carbon dioxide (VE/VCO2) at anaerobic threshold (AT) >34.3, optimized cut-point). Only LVEF and VE/VCO2 at AT were significant predictors of major CV events. The lower LVEF subgroup (LVEF ≤ 39%) was associated with an increased risk of CV events, relative to the LVEF ≥75% subgroup, except for patients with ventilatory inefficiency (p = 0.400). In conclusion, ventilatory inefficiency influenced the prognostic predictability of LVEF in reduced LVEF outpatients. Ventilatory inefficiency can be used as a therapeutic target in HF management.

Prognostic significance of cardiac I-123-metaiodobenzylguanidine imaging in patients with reduced, mid-range, and preserved left ventricular ejection fraction admitted for acute decompensated heart failure: a prospective study in Osaka Prefectural Acute Heart Failure Registry (OPAR).

Cardiac 123I-metaiodobenzylguanidine (123I-MIBG) imaging provides prognostic information in patients with chronic heart failure (HF). However, there is little information available on the prognostic role of cardiac 123I-MIBG imaging in patients admitted for acute decompensated heart failure (ADHF), especially relating to reduced ejection fraction [HFrEF; left ventricular ejection fraction (LVEF) < 40%], mid-range ejection fraction (HFmrEF; 40% ≤ LVEF < 50%) and preserved ejection fraction (HFpEF; LVEF ≥ 50%). We studied 349 patients admitted for ADHF and discharged with survival. Cardiac 123I-MIBG imaging, echocardiography, and venous blood sampling were performed just before discharge. The cardiac 123I-MIBG heart-to-mediastinum ratio (late H/M) was measured on the chest anterior view images obtained at 200 min after the isotope injection. The endpoint was cardiac events defined as unplanned HF hospitalization and cardiac death. During a follow-up period of 2.1 ± 1.4 years, 128 patients had cardiac events (45/127 in HFrEF, 28/78 in HFmrEF, and 55/144 in HFpEF). On multivariable Cox analysis, late H/M was significantly associated with cardiac events in overall cohort (P = 0.0038), and in subgroup analysis of each LVEF subgroup (P = 0.0235 in HFrEF, P = 0.0119 in HFmEF and P = 0.0311 in HFpEF). Kaplan-Meier analysis showed that patients with low late H/M (defined by median) had significantly greater risk of cardiac events in overall cohort (49% vs. 25% P < 0.0001) and in each LVEF subgroup (HFrEF: 48% vs. 23% P = 0.0061, HFmrEF: 51% vs. 21% P = 0.0068 and HFpEF: 50% vs. 26% P = 0.0026). Cardiac sympathetic nerve dysfunction was associated with poor outcome in ADHF patients irrespective of HFrEF, HFmrEF, or HFpEF.

Fragility is a key determinant of survival in heart failure patients

BackgroundHeart failure (HF) is a chronic condition with poor prognosis, and has a high prevalence among older adults. Due to older age, fragility is often present among HF patients. However, even young HF patients show a high degree of fragility. The effect of fragility on long-term prognosis in HF patients, irrespective of age, remains unexplored. The aim of this study was to assess the influence of fragility on long-term prognosis in outpatients with HF. Methods and resultsAt least one abnormal evaluation among four standardized geriatric scales was used to identify fragility. Predefined criteria for such scales were: Barthel Index, <90; OARS scale, <10 in women and <6 in men; Pfeiffer Test, >3 (±1, depending on educational grade); and ≥1 positive response for depression on the abbreviated Geriatric Depression Scale (GDS). We assessed 1314 consecutive HF outpatients (27.8% women, mean age years 66.7±12.4years with different etiologies. Fragility was detected in 581 (44.2%) patients. 626 deaths occurred during follow-up; the median follow-up was 3.6years [P25–P75: 1.8–6.7] for the total cohort, and 4.9years [P25–P75: 2.5–8.4] for living patients. Fragility and its components were significantly associated with decreased survival by univariate analysis. In a comprehensive multivariable Cox regression analysis, fragility remained independently associated with survival in the entire cohort, and in age and left ventricular ejection fraction subgroups. ConclusionFragility is a key determinant of survival in ambulatory patients with HF across all age strata.