Heart Failure And Reduced Ejection Fraction Research Articles

Depressive symptoms are associated with clinical outcomes in heart failure with reduced ejection fraction.

The objective of this study was to examine associations between elevated depressive symptoms and increased risk of adverse clinical events patients with heart failure and reduced ejection fraction (HFrEF), as well as the potential contribution of health behaviours. One hundred forty-two men and women with HFrEF were enrolled through heart failure (HF) clinics and followed over time. At baseline and 6months, depressive symptoms were assessed by the Beck Depression Inventory-II (BDI-II) and HFrEF disease activity by B-type natriuretic peptide (BNP). The Self-Care of Heart Failure Index (SCHFI) was used to assess HF self-care behaviours. Proportional hazards regression models assessed the contribution of depressive symptoms and HFrEF disease biomarkers on death or cardiovascular hospitalization. Over a median follow-up period of 4years, 42 patients (30%) died, and 84 (60%) had cardiovascular hospitalizations. A 10-point higher baseline BDI-II score was associated with a 35% greater risk of death or cardiovascular hospitalization. Higher baseline BDI-II scores were associated with poorer HF self-care maintenance behaviours (R=-0.30, P<0.001) and fewer daily steps (R=-0.19, P=0.04), suggesting that elevated depressive symptoms may diminish important health behaviours. Increases in plasma BNP over 6months were associated with worse outcomes. Changes in BDI-II and plasma BNP over 6months were positively related (R=0.25, P=0.004). This study confirms that elevated depressive symptoms are associated with an increased likelihood of adverse clinical outcomes in patients with HFrEF. Poor health behaviours may contribute to the adverse association of elevated depressive symptoms with the increased hazard of adverse clinical outcomes.

Dapagliflozin and quality of life measured using the EuroQol 5-dimension questionnaire in patients with heart failure with reduced and mildly reduced/preserved ejection fraction.

Although much is known about the usefulness of heart failure (HF)-specific instruments for assessing patient well-being, less is known about the value of generic instruments for the measurement of health-related quality of life (HRQL) in HF. The aim of this study was to assess the relationship between the EuroQol 5-dimension 5-level (EQ-5D-5L) visual analogue scale (VAS) and index scores, clinical characteristics, and outcomes in patients with HF and the effect of dapagliflozin on these scores. We performed a patient-level pooled analysis of the DAPA-HF and DELIVER trials, which investigated the effectiveness and safety of dapagliflozin in patients with HF and reduced ejection fraction (HFrEF) and mildly reduced/preserved ejection fraction (HFmrEF/HFpEF), respectively. Patients reporting higher (better) EQ-5D-5L VAS and index scores had a lower prevalence of comorbidities, including atrial fibrillation and hypertension, than patients with a worse score. They were also more likely to have better investigator-reported (New York Heart Association class) and patient-self-reported (Kansas City Cardiomyopathy Questionnaire) health status and lower median N-terminal pro-B-type natriuretic peptide levels. Compared to patients with the lowest scores (Q1), those with higher EQ-5D-5L VAS scores had better outcomes: the hazard ratio for the composite of cardiovascular death or worsening HF was 0.81 (95% confidence interval 0.72-0.91) in Q2, 0.74 (0.65-0.84) in Q3, and 0.62 (0.54-0.72) in Q4. The risk of each component of the composite outcome, and all-cause death, was also lower in patients with better scores. Similar findings were observed for the index score. Treatment with dapagliflozin improved both EQ-5D-5L VAS and index scores across the range of ejection fraction. Both higher (better) EQ-5D-5L VAS and index scores were associated with better outcomes. Dapagliflozin treatment improved EQ-5D-5L VAS and index scores, irrespective of ejection fraction.

ENHANCING FUNCTIONAL CAPACITY AND QUALITY OF LIFE WITH ECCENTRIC CYCLING TRAINING IN HEART FAILURE PATIENTS: A RANDOMIZED CONTROLLED TRIAL

INTRODUCTION Exercise training is recommended for comprehensive management of patients with heart failure and reduced ejection fraction (HFrEF). However, limited exercise capacity prevents many patients from gaining optimal training benefit. Given eccentric cycling is well tolerated in HFrEF, and enables greater power output, we hypothesized that eccentric cycling training would result in superior functional outcomes than concentric cycling training when the interventions were matched for heart rate (HR). METHODS Forty-five participants (9♀, 57±13 y; BMI 27±5 kg/m2) with HFrEF (ejection fraction 33±10%, New York Heart Association class II) were randomized in a 1:1 superiority clinical trial to either eccentric cycling training (ET, n = 25) or concentric cycling training (CT, n = 20). Each intervention involved 2-weeks of familiarization and 12-weeks of training at matched relative intensity (40-80% of HR reserve), twice weekly. Primary outcome was peak oxygen consumption (V̇O2peak), secondary outcomes included 6-minute walk, functional lower extremity strength and health-related quality of life (Minnesota Living with Heart Failure, MLHF). RESULTS Repeated measures ANOVA revealed significant interaction effects for 6-min walk (ET 476±77 to 547±80 m vs CT 485±106 to 516±113 m, P=0.015), 30s sit-to-stand (ET 12±3 to 16±3 repetitions vs CT 13±4 to 14±3 repetitions, P=0.002), and timed up-and-go (ET 7.2±1.2 to 6.2±1.1 s vs CT 7.6±1.5 to 7.3±1.9 s, P=0.019). There were significant time effects for V̇O2peak (ET: 17.7±4.8 to 19.1±5.2 ml/kg/min and CT 17.4±6.0 to 19.8±6.0 ml/kg/min, P&amp;lt;0.001), and MLWHF (ET 31±24 to 23±16 and CT 32±19 to 27±16, P=0.003). CONCLUSION When matched for heart rate to control cardiovascular burden, ET demonstrated superior effect in functional capacity, and similar benefits in aerobic capacity (V̇O2peak) and health-related quality of life, when compared to CT. ET is a novel and efficacious approach for clinical benefit in highly compromised HFrEF patients, who represent a challenge in terms of exercise prescription.

How to Manage Beta-Blockade in Older Heart Failure Patients: A Scoping Review.

Beta blockers (BBs) play a crucial role in enhancing the quality of life and extending the survival of patients with heart failure and reduced ejection fraction (HFrEF). Initiating the therapy at low doses and gradually titrating the dose upwards is recommended to ensure therapeutic efficacy while mitigating potential adverse effects. Vigilant monitoring for signs of drug intolerance is necessary, with dose adjustments as required. The management of older HF patients requires a case-centered approach, taking into account individual comorbidities, functional status, and frailty. Older adults, however, are often underrepresented in randomized clinical trials, leading to some uncertainty in management strategies as patients with HF in clinical practice are older than those enrolled in trials. The present article performs a scoping review of the past 25 years of published literature on BBs in older HF patients, focusing on age, outcomes, and tolerability. Twelve studies (eight randomized-controlled and four observational) encompassing 26,426 patients were reviewed. The results indicate that BBs represent a viable treatment for older HFrEF patients, offering benefits in symptom management, cardiac function, and overall outcomes. Their role in HF with preserved EF, however, remains uncertain. Further research is warranted to refine treatment strategies and address specific aspects in older adults, including proper dosing, therapeutic adherence, and tolerability.

Unraveling the Predictors for Delirium and ICU Stay Duration in Patients with Heart Failure and Reduced Ejection Fraction (HFrEF) Undergoing Coronary Artery Bypass Grafting-A Multicentric Analysis.

Objective: This study assesses predictors for postoperative delirium (POD) and ICU stay durations in HFrEF patients undergoing CABG, focusing on ONCAB versus OPCAB surgical methods. Summary Background Data: In cardiac surgery, especially CABG, POD significantly impacts patient recovery and healthcare resource utilization. With varying incidences based on surgical techniques, this study provides an in-depth analysis of POD in the context of HFrEF patients, a group particularly susceptible to this complication. Methods: A retrospective analysis of 572 patients who underwent isolated CABG surgery with a preoperative ejection fraction under 40% was conducted at four German university hospitals. Patients were categorized into ONCAB and OPCAB groups for comparative analysis. Results: Age and Euro Score II were significant predictors of POD. The ONCAB group showed higher incidences of re-sternotomy (OR: 3.37), ECLS requirement (OR: 2.29), and AKI (OR: 1.49), whereas OPCAB was associated with a lower incidence of delirium. Statistical analysis indicated a significant difference in ICU stay durations between the two groups, influenced by surgical complexity and postoperative complications. Conclusions: This study underscores the importance of surgical technique in determining postoperative outcomes in HFrEF patients undergoing CABG. OPCAB may offer advantages in reducing POD incidence. These findings suggest the need for tailored surgical decisions and comprehensive care strategies to enhance patient recovery and optimize healthcare resources.

Electrocardiographic predictors of response to sacubitril/valsartan therapy in heart failure with reduced ejection fraction

BackgroundSacubitril/valsartan (SV) is currently recommended as a first-line therapy in patients with heart failure and reduced ejection fraction (HFrEF) due to its significant clinical and prognostic benefit; however, not all patients respond to therapy and predictors of clinical response to SV remain under-studied. AimsTo identify electrocardiographic (ECG) predictors of response to SV therapy in HFrEF patients. MethodsA retrospective analysis of a hospital heart failure registry was undertaken. Consecutive HFrEF patients (New York Heart Association class II–III) on maximal-dose SV were studied. Response to SV was defined as ≥10% relative improvement in left ventricular ejection fraction (LVEF) at 3-months post-maximal-dose therapy. Pre-therapy ECGs were retrospectively analyzed for axes and standard wave and interval durations. Logistic regression was used to estimate odds ratios and 95% confidence intervals for associations between predictors and therapeutic response. Backward stepwise regression was employed to develop a parsimonious model. ResultsP-wave duration (PWD) 100–120 ms, PWD >120 ms, and QTc >460 ms were associated with response to SV on univariate analysis: OR 18.00 (4.45–122.90), 5.00 (1.47–20.42), and 3.10 (1.18–9.22), respectively. The preferred model that included the former two predictors in combination with pre-therapy creatinine, mineralocorticoid receptor antagonist use, and LVEF was highly selective (area under the ROC curve = 0.868). ConclusionsProlongation of both PWD and QTc interval on baseline ECG in HFrEF patients is predictive of therapeutic response to maximal-dose SV therapy and may indicate early cardiac remodeling that is highly amenable to reversal.

Sodium-glucose cotransporter 2 inhibitors influence skeletal muscle pathology in patients with heart failure and reduced ejection fraction.

Patients with heart failure and reduced ejection fraction (HFrEF) exhibit skeletal muscle pathology, which contributes to symptoms and decreased quality of life. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) improve clinical outcomes in HFrEF but their mechanism of action remains poorly understood. We aimed, therefore, to determine whether SGLT2i influence skeletal muscle pathology in patients with HFrEF. Muscle biopsies from 28 male patients with HFrEF (New York Heart association class I-III) treated with SGLT2i (>12 months) or without SGLT2i were compared. Comprehensive analyses of muscle structure (immunohistochemistry), transcriptome (RNA sequencing), and metabolome (liquid chromatography-mass spectrometry) were performed, and serum inflammatory profiling (ELISA). Experiments in mice (n = 16) treated with SGLT2i were also performed. Myofiber atrophy was ~20% less in patients taking SGLT2i (p = 0.07). Transcriptomics and follow-up measures identified a unique signature in patients taking SGLT2i related to beneficial effects on atrophy, metabolism, and inflammation. Metabolomics identified influenced tryptophan metabolism in patients taking SGLT2i: kynurenic acid was 24% higher and kynurenine was 32% lower (p < 0.001). Serum profiling identified that SGLT2i treatment was associated with lower (p < 0.05) pro-inflammatory cytokines by 26-64% alongside downstream muscle interleukin (IL)-6-JAK/STAT3 signalling (p = 008 and 0.09). Serum IL-6 and muscle kynurenine were correlated (R = 0.65; p < 0.05). Muscle pathology was lower in mice treated with SGLT2i indicative of a conserved mammalian response to treatment. Treatment with SGLT2i influenced skeletal muscle pathology in patients with HFrEF and was associated with anti-atrophic, anti-inflammatory, and pro-metabolic effects. These changes may be regulated via IL-6-kynurenine signalling. Together, clinical improvements following SGLT2i treatment in patients with HFrEF may be partly explained by their positive effects on skeletal muscle pathology.

Efficacy of Sacubitril-Valsartan on Survival and Cardiac Remodeling in Hypotensive Heart Failure With Reduced Ejection Fraction: A Multicenter Study

ObjectiveTo investigate whether hypotensive patients diagnosed with heart failure and reduced ejection fraction (HFrEF) might benefit from angiotensin receptor–neprilysin inhibitors (ARNis) in real-world practice because patients with baseline systolic blood pressure (SBP) of less than 100 mm Hg have been excluded from landmark trials. Patients and MethodsIn this multicenter study conducted between January 1, 2013, and December 31, 2021, a total of 7562 symptomatic patients with HFrEF were enrolled and grouped by SBP (hypotension was defined as an SBP of less than 100 mm Hg) and ARNi use as follows: group 1, hypotensive/non-ARNi users (n=484); group 2, hypotensive/ARNi users (n=308); group 3, nonhypotensive/non-ARNi users (n=4560); and group 4, nonhypotensive/ARNi users (n=2210). Inverse probability of treatment weighting was used to balance baseline characteristics for survival analysis. ResultsDiverse baseline characteristics and lower rates of medication use were found among non-ARNi users compared with ARNi users. Hypotensive/ARNi users had lower ARNi initiation doses than nonhypotensive/ARNi users. We observed significantly lower mortality, composite heart failure hospitalization, and CV death for hypotensive/ARNi and the other 2 nonhypotensive groups (groups 3 and 4) during a median follow-up of 3.43 years (all P<.05), with a similar effect on reverse remodeling for the hypotensive/ARNi group compared with the hypotensive/non-ARNi group. The event-free survival benefits of ARNi vs renin-angiotensin system inhibitors were consistent with the lower boundary of SBP for clinical benefits found until 88 mm Hg (spline curves) after inverse probability of treatment weighting. ConclusionPatients with HFrEF and hypotension may still benefit from ARNi treatment. Patients with hypotensive HFrEF should not be routinely excluded from ARNi use in a real-world setting.

Taiwan Society of Cardiology Heart Failure Registry 2020: Rationale and Design.

Heart failure (HF) is a significant public health problem worldwide. Death and rehospitalization rates are similar across different HF phenotypes. However, the existing Taiwanese HF registries mainly enrolled inpatients with HF and reduced ejection fraction (HFrEF) before 2019, so their results may not apply to outpatients or patients with HF with mildly reduced ejection fraction (HFmrEF) and HF with preserved ejection fraction (HFpEF) phenotypes. The Taiwan Society of Cardiology Heart Failure Registry 2020 is a prospective, multicenter, observational registry that will enroll patients with HF from 27 hospitals in Taiwan between 2020 and 2022 and will be followed for two years. Patients eligible for enrollment include those admitted due to acute decompensated heart failure or outpatients with a history of hospitalization for heart failure within the past six months. The registry will collect patient demographics, medical history, HF diagnosis, medication use, examination results, and comorbidities. The registry plans to enroll 3,370 patients, with the distribution of HFrEF/HFmrEF/HFpEF as 59%/13%/28%. Follow-up intervals will occur every six months for up to two years to monitor clinical outcomes and major cardiac interventions. The registry will conclude in December 2024. The Taiwan Society of Cardiology Heart Failure Registry 2020 is a comprehensive and meticulous effort to demonstrate the epidemiology, adherence to guidelines, clinical outcomes, and disease progression of Taiwanese patients with HF in contemporary clinical practice.

Educational status affects prognosis of patients with heart failure with reduced ejection fraction: A post-hoc analysis from the WARCEF trial.

The influence of social determinants of health (SDOH) on the prognosis of Heart Failure and reduced Ejection Fraction (HFrEF) is increasingly reported. We aim to evaluate the contribution of educational status on outcomes in patients with HFrEF. We used data from the WARCEF trial, which randomized HFrEF patients with sinus rhythm to receive Warfarin or Aspirin; educational status of patients enrolled was collected at baseline. We defined three levels of education: low, medium and high level, according to the highest qualification achieved or highest school grade attended. We analysed the impact of the educational status on the risk of the primary composite outcome of all-cause death, ischemic stroke (IS) and intracerebral haemorrhage (ICH); components of the primary outcome were also analysed as secondary outcomes. 2295 patients were included in this analysis; of these, 992 (43.2%) had a low educational level, 947 (41.3%) had a medium education level and the remaining 356 (15.5%) showed a high educational level. Compared to patients with high educational level, those with low educational status showed a high risk of the primary composite outcome (adjusted hazard ratio [aHR]: 1.31, 95% confidence intervals [CI] 1.02-1.69); a non-statistically significant association was observed in those with medium educational level (aHR: 1.20, 95%CI: .93-1.55). Similar results were observed for all-cause death, while no statistically significant differences were observed for IS or ICH. Compared to patients with high educational levels, those with low educational status had worse prognosis. SDOH should be considered in patients with HFrEF. NCT00041938.

Cardiac Troponin and Treatment Effects of Omecamtiv Mecarbil: Results From the GALACTIC-HF Study

BackgroundOmecamtiv mecarbil improves outcomes in patients with heart failure and reduced ejection fraction (HFrEF). We examined the relationship between baseline troponin, change in troponin over time, and the treatment effect of omecamtiv mecarbil in patients enrolled in the Global Approach to Lowering Adverse Cardiac Outcomes through Improving Contractility in Heart Failure (GALACTIC-HF) trial (NCT02929329). MethodsGALACTIC-HF was a double-blind, placebo-controlled trial that randomized 8256 patients with symptomatic HFrEF to omecamtiv mecarbil or placebo. High sensitivity troponin I (cTnI) was measured serially at a core laboratory. We analyzed the relationship between both baseline cTnI and change in cTnI concentrations with clinical outcomes and the treatment effect of omecamtiv mecarbil. ResultsHigher baseline cTnI concentrations were associated with a risk of adverse outcomes (hazard ratio for the primary endpoint of time to first HF event or CV death = 1.30; 95% CI 1.28, 1.33, p < 0.001 per doubling of baseline cTnI). Although the incidence of safety outcomes was higher in patients with higher baseline cTnI, there was no difference between treatment groups. Treatment with omecamtiv mecarbil led to a modest increase in cTnI that was related to plasma concentrations of omecamtiv mecarbil and peaked at 6 weeks. An increase in troponin from baseline to week 6 was associated with an increased risk of the primary endpoint (p < 0.001) which was similar regardless of treatment assignment (p value for interaction = 0.2). ConclusionsIn a cohort of patients with HFrEF, baseline cTnI concentrations were strongly associated with adverse clinical outcomes. Although cTnI concentrations were increased in patients treated with omecamtiv mecarbil, we did not find a differential effect of omecamtiv mecarbil on either safety or efficacy based on baseline cTnI status or change in cTnI.

Defining iron replete status in patients with heart failure treated with intravenous iron

Iron deficiency is an important therapeutic target in patients with heart failure and reduced ejection fraction (HFrEF). Over the past two decades, several trials of intravenous (IV) iron supplementation in HFrEF have shown favorable effects on symptoms, functional status, and heart failure (HF) hospitalizations...

Defining iron replete status in patients with heart failure treated with intravenous iron

Iron deficiency is an important therapeutic target in patients with heart failure and reduced ejection fraction (HFrEF). Over the past two decades, several trials of intravenous (IV) iron supplementation in HFrEF have shown favorable effects on symptoms, functional status, and heart failure (HF) hospitalizations...

Defining iron replete status in patients with heart failure treated with intravenous iron

Iron deficiency is an important therapeutic target in patients with heart failure and reduced ejection fraction (HFrEF). Over the past two decades, several trials of intravenous (IV) iron supplementation in HFrEF have shown favorable effects on symptoms, functional status, and heart failure (HF) hospitalizations...

Impact of the COVID-19 pandemic on implementation of novel guideline-directed medical therapies for heart failure in Germany: a nationwide retrospective analysis.

Guideline-directed medical therapy (GDMT) is the cornerstone in the treatment of patients with heart failure and reduced ejection fraction (HFrEF) and novel substances such as sacubitril/valsartan (S/V) and sodium-glucose co-transporter-2 inhibitors (SGLT2i) have demonstrated marked clinical benefits. We investigated their implementation into real-world HF care in Germany before, during, and after the COVID-19 pandemic period. The IQVIA LRx data set is based on ∼80% of 73 million people covered by the German statutory health insurance. Prescriptions of S/V were used as a proxy for HFrEF. Time trends were analysed between Q1/2016 and Q2/2023 for prescriptions for S/V alone and in combination therapy with SGLT2i. The number of patients treated with S/V increased from 5260 in Q1/2016 to 351,262 in Q2/2023. The share of patients with combination therapy grew from 0.6% (29 of 5260) to 14.2% (31,128 of 219,762) in Q2/2021, and then showed a steep surge up to 54.8% (192,429 of 351,262) in Q2/2023, coinciding with the release of the European Society of Cardiology (ESC) guidelines for HF in Q3/2021. Women and patients aged >80 years were treated less often with combined therapy than men and younger patients. With the start of the COVID-19 pandemic, the number of patients with new S/V prescriptions dropped by 17.5% within one quarter, i.e., from 26,855 in Q1/2020 to 22,145 in Q2/2020, and returned to pre-pandemic levels only in Q1/2021. The COVID-19 pandemic was associated with a 12-month deceleration of S/V uptake in Germany. Following the release of the ESC HF guidelines, the combined prescription of S/V and SGLT2i was readily adopted. Further efforts are needed to fully implement GDMT and strengthen the resilience of healthcare systems during public health crises. Supported by Novartis Pharma GmbH, Nuremberg, Germany.

Beta-blocker management in patients admitted for acute heart failure and reduced ejection fraction: a review and expert consensus opinion.

The role of the beta-adrenergic signaling pathway in heart failure (HF) is pivotal. Early blockade of this pathway with beta-blocker (BB) therapy is recommended as the first-line medication for patients with HF and reduced ejection fraction (HFrEF). Conversely, in patients with severe acute HF (AHF), including those with resolved cardiogenic shock (CS), BB initiation can be hazardous. There are very few data on the management of BB in these situations. The present expert consensus aims to review all published data on the use of BB in patients with severe decompensated AHF, with or without hemodynamic compromise, and proposes an expert-recommended practical algorithm for the prescription and monitoring of BB therapy in critical settings.

Effect of empagliflozin on CMR-estimated pulmonary capillary wedge pressure in patients with type 2 diabetes, or prediabetes, and heart failure with reduced ejection fraction (SUGAR-DM-HF)

Abstract Background/Introduction Pulmonary capillary wedge pressure (PCWP) is a measure of left ventricular (LV) filling pressure usually invasively assessed during right heart catheterisation. A cardiac magnetic resonance (CMR) imaging-based model to non-invasively estimate PCWP was recently developed. Purpose In this exploratory analysis of the SUGAR-DM-HF trial (NCT03485092) we assessed the association of CMR-estimated PCWP (CMR-PCWP) with other imaging and circulating biomarker measures of congestion in patients with heart failure and reduced ejection fraction (HFrEF) and type 2 diabetes or prediabetes. We also investigated the effect of empagliflozin on CMR-PCWP and the relationship between CMR-PWCP and the remodelling effect of empagliflozin. Methods A total of 105 patients with HFrEF were randomly assigned 1:1 to empagliflozin 10 mg once daily or placebo. CMR-PCWP and other ultrasound and circulating biomarker measures of congestion were estimated at baseline and 36 weeks. CMR-PCWP (mmHg) was calculated using the formula: 6.1352 + (0.07204*left atrial volume) + (0.02256*LV mass). Results 105 patients with HFrEF, mean age 69 years, 73% males, mean left ventricular ejection (LVEF) 33% were randomised. Mean baseline CMR-PCWP was 15.0 mmHg. CMR-PCWP was ≥15 mmHg in 52 (50% patients) at baseline. At baseline, patients with higher PCWP (≥15 mmHg) were more frequently male, had higher body mass index, higher N-terminal pro-B-type natriuretic peptide (NT-proBNP), and a greater number of B-lines on lung ultrasound (LUS). Peripheral oedema was present in 69% and 57% of patients with higher PCWP and lower PCWP, respectively (p = 0.18). Pulmonary crepitations were present in 13% and 11% of patients with higher and lower PCWP, respectively (p = 0.74). At baseline, CMR-derived PCWP correlated with log-NT-proBNP (r = 0.31, p&amp;lt;0.001), left atrial (LA) volume (r = 0.94, p&amp;lt;0.001), E/e’ (r = 0.36, p = 0.02), MRI-derived LV volumes (LV end-systolic volume: r = 0.56 p&amp;lt;0.001; LV end-diastolic volume: r = 0.62 p&amp;lt;0.001), LVEF (r=-0.26 p = 0.01), and right ventricular (RV) volumes (RV end-systolic volume: r = 0.56 p&amp;lt;0.001; RV end-diastolic volume: r = 0.61 p&amp;lt;0.001). Mean CMR-PCWP decreased from baseline to 36 weeks by -0.37 (95% CI -0.78 to 0.05) mmHg and -0.17 (95% CI -0.69 to 0.36) mmHg in the empagliflozin and placebo groups, respectively; placebo-corrected difference -0.43 mmHg (95% CI -1.09 to 0.23), p = 0.20 (Figure 1). The beneficial effect of empagliflozin on reducing LV end-systolic volume index was not modified by baseline CMR-PCWP (p interaction = 0.98). Conclusions In patients with HFrEF, higher non-invasively measured CMR-derived PCWP was associated with NT-proBNP, MRI-derived LV and RV volumes and LUS markers of congestion. There were no between group difference in CMR-derived PCWP, although this study was not powered for this outcome.Figure 1

The effect of iron deficiency treatment with intravenous ferric carboxymaltose on the arrhythmic burden of patients with HFrEF and cardiac implantable electronic devices

Abstract Background The deleterious effect of iron deficiency (ID) on cardiomyocyte electrochemical stability is well-documented. In patients with heart failure and reduced ejection fraction (HFrEF), ID represents a key comorbidity associated with increased morbidity and mortality. Thus, it has been hypothesized that treating ID may lead to reduced incidence of arrhythmias in HFrEF patients. Purpose To study the effect of intravenous ferric carboxymaltose (IV FCM) treatment on the iron stores, arrhythmic burden, functional capacity and quality of life in HFrEF patients with ID and cardiac implantable electronic devices (CIEDs). Methods Patients with HFrEF, ID and CIEDs scheduled to receive IV FCM as per ESC guidelines were invited to participate. Follow-up lasted 12 months. The primary outcome was related to the amelioration of patients’ iron status. Secondary outcomes relative to arrhythmic burden included (i) the incidence of device-detected ventricular tachycardias (VTs) between the year before recruitment to the study and the follow-up period, (ii) patients’ Lown and Wolf classification as derived from 24hour Holter monitoring. Data related to non-invasive arrhythmic markers such as late potential, microvolt T-wave alternans and deceleration capacity were also available. Results This real-life cohort included 79 patients (84% male). Patients’ median age was 70.8 [IRQ:11.7] years. Median ferritin increased to 150 [125] ng/mL at 12 months (baseline 55 [68] ng/mL, P&amp;lt;0.001). At their final visit, 45 (57%) patients no longer met the ESC criteria for iron deficiency (P&amp;lt;0.001). The CIED-derived incidence of VT episodes decreased significantly after 12 months of IV FCM treatment (0.26±0.83 episodes per patient per year compared to 0.8±2.36, P = 0.048). Patients were also significantly likely to shift to a more favorable Lown and Wolf arrhythmic burden classification (P = 0.01). Patients’ late potential results and microvolt T-wave alternans also improved significantly (P = 0.01 for both tests). Conclusion The results of this real-life cohort analysis suggest significant reduction of the arrhythmic burden in HFrEF and ID after restitution of iron stores. Further studies are needed to further evaluate the impact of these results.

Relationship between change in Kansas City Cardiomyopathy Questionnaire scores and outcomes in patients with HFrEF

Abstract Background Although a 5-point change in Kansas City Cardiomyopathy Questionnaire (KCCQ) scores is widely recognized as representing a clinically meaningful change in symptoms and quality of life, it is not known how changes KCCQ scores relate to risk of hospitalization and death. Purpose To evaluate how changes in KCCQ summary scores relate to subsequent risk of hospitalization and death in a large cohort of patients with heart failure and reduced ejection fraction (HFrEF). Methods We used individual patient data from 3 HFrEF trials (ATMOSPHERE, PARADIGM-HF, and DAPA-HF) to examine the association between changes in KCCQ summary scores between baseline and 8-months and the subsequent risk of cardiovascular death or HF hospitalization, using Cox-proportional hazard models. Change in score was categorized as very small (&amp;gt;0 &amp;lt;5), small (&amp;gt; = 5 &amp;lt;10), moderate (&amp;gt; = 10 &amp;lt;20), and large (&amp;gt; = 20) points. We examined the KCCQ total symptom score (KCCQ-TSS), KCCQ clinical summary score (KCCQ-CSS), and KCCQ overall summary score (KCCQ-OSS). Results Among 15,892 participants with HFrEF, 1403 patients (8.8%) had a large deterioration in KCCQ score, 1688 (10.6%) a moderate deterioration, 1442 (9.1%) a small deterioration, 1527 (9.6%) a very small deterioration, and 2326 (14.6%) no deterioration. Conversely, 1836 patients (11.6%) had a very small improvement, 1732 (10.9%) a small improvement, 2202 (13.9%) a moderate improvement, and 1736 (10.9%) a large improvement. Patients with larger changes in KCCQ scores were older and more often female and had lower baseline summary scores and worse heart failure characteristics. Worsening heath status i.e., decrease in the KCCQ-TSS, was associated with a higher risk of the composite outcome (and each of its components), as well as all-cause mortality (Figure 1). On the contrary, improvements in KCCQ-TSS were not associated with better clinical outcomes (Figure 1). The findings were similar for 4-month changes of KCCQ-TSS, and changes in other KCCQ scores (KCCQ-CSS and KCCQ-OSS) at both 4 and 8-months. Conclusion Decreases (deterioration) in KCCQ summary scores during follow-up were associated with worse outcomes in patients with HFrEF but no association was seen between improvement in KCCQ scores and outcomes. These findings have potential implications for the interpretation of the effect of treatment on KCCQ scores.

Effect of eplerenone according to duration of heart failure in EMPHASIS-HF: It is never too late to start an MRA in HFrEF

Abstract Background In the Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure trial (EMPHASIS-HF), the mineralocorticoid receptor antagonist (MRA) eplerenone reduced both the risk of death and heart failure (HF) hospitalization in patients with HF and reduced ejection fraction (HFrEF) and mild symptoms. However, many patients are still not prescribed an MRA and physicians may be reluctant to add another treatment in patients with longstanding HF who appear to be "stable" on their current therapy. Purpose As little is known about how the effect of MRA therapy varies by the duration of HF, we examined the efficacy of eplerenone according to time from HF diagnosis among patients in EMPHASIS-HF. The primary trial outcome was the composite of a first hospitalization for HF or cardiovascular death. Methods Three patient groups of similar size were created according to the duration of HF: &amp;lt;1 year, ≥1 to &amp;lt;5 years, and ≥5 years. Outcomes were analysed using Cox regression and the Kaplan-Meier estimate. Treatment effects were examined according to HF duration category and also using the duration of HF as a continuous variable. Results The number of patients in each group was: 975 (&amp;lt;1 year), 769 (1 - &amp;lt;5 years), and 988 (≥5 years), respectively. Patients with longer duration of HF were older and more frequently had an ischaemic aetiology of HF. Additionally, a longer duration of HF was associated with lower eGFR levels, wider QRS duration, and a higher proportion of atrial fibrillation at baseline. The rate of the primary outcome (per 100 person-year) increased with HF duration: 9.8 (95% CI: 8.4-11.4) for &amp;lt;1 year, 13.5 (11.6-15.7) for 1 - &amp;lt;5 years, and 17.6 (15.6-19.8) for ≥5 years. Similar trends were seen in all other outcomes (Figure 1). The hazard ratios for the effect of eplerenone compared to placebo on the primary outcome were 0.57 (95% CI: 0.42-0.79) for &amp;lt;1 year, 0.81 (0.60-1.10) for 1- &amp;lt;5 years, and 0.61 (0.48-0.78) for ≥5 years; P for interaction = 0.24. The benefits of eplerenone were also consistent across the duration of HF examined as a continuous variable (Figure 2). For the primary outcome, The number needed to treat (NNT) over the duration of the trial, for the primary outcome, was 14 for &amp;lt;1 year, 13 for 1 - &amp;lt;5 years and only 10 for ≥5 years duration. Conclusions Patients with a longer duration of HF had worse clinical status and a higher rate of events, but the benefit of eplerenone was consistent in people with longer-standing HF and HF of shorter duration. These data suggest that it is never too late to start an MRA in patients with HFrEF. Figure 1. Outcomes according to heart failure duration category Abbreviations: CV cardiovascular; HF heart failure Figure 2. Treatment effects according to the duration of heart failure Abbreviations: CV cardiovascular; HF heart failureFigure 1Figure 2