Management Of Heart Failure With Reduced Ejection Fraction Research Articles

Effects of trimetazidine on heart failure with reduced ejection fraction and associated clinical outcomes: a systematic review and meta-analysis

BackgroundDespite maximal treatment, heart failure (HF) remains a major clinical challenge. Besides neurohormonal overactivation, myocardial energy homoeostasis is also impaired in HF. Trimetazidine has the potential to restore myocardial energy...

Beyond Quadruple Therapy and Current Therapeutic Strategies in Heart Failure with Reduced Ejection Fraction: Medical Therapies with Potential to Become Part of the Therapeutic Armamentarium.

Heart failure with reduced ejection fraction (HFrEF) is a complex clinical syndrome with significant morbidity and mortality and seems to be responsible for approximately 50% of heart failure cases and hospitalizations worldwide. First-line treatments of patients with HFrEF, according to the ESC and AHA guidelines, include β-blockers, angiotensin receptor/neprilysin inhibitors, sodium-glucose cotransporter 2 inhibitors, and mineralocorticoid receptor antagonists. This quadruple therapy should be initiated during hospital stay and uptitrated to maximum doses within 6 weeks after discharge according to large multicenter controlled trials. Quadruple therapy improves survival by approximately 8 years for a 55-year-old heart failure patient. Additional therapeutic strategies targeting other signaling pathways such as ivabradine, digoxin, and isosorbide dinitrate and hydralazine combination for African Americans, as well as adjunctive symptomatic therapies, seem to be necessary in the management of HFrEF. Although second-line medications have not achieved improvements in mortality, they seem to decrease heart failure hospitalizations. There are novel medical therapies including vericiguat, omecamtiv mecarbil, genetic and cellular therapies, and mitochondria-targeted therapies. Moreover, mitraclip for significant mitral valve regurgitation, ablation in specific atrial fibrillation cases, omecamtiv mecarbil are options under evaluation in clinical trials. Finally, the HeartMate 3 magnetically levitated centrifugal left ventricular assist device (LVAD) has extended 5-year survival for stage D HF patients who are candidates for an LVAD.

Optimization of GDMT for patients with heart failure and reduced ejection fraction: can physiological and biological barriers explain the gaps in adherence to heart failure guidelines?

Heart failure is a growing epidemic with high mortality rates and recurrent hospital admissions that creates a burden on affected individuals, their caregivers and the whole healthcare system. Throughout the years, many randomized trials have established the effectiveness of several pharmacological therapies and electrophysiological devices to reduce hospitalizations and improve quality of life and survival, mostly for patients with heart failure with reduced ejection fraction (HFrEF). These studies led to the publication of national societies' recommendations to guide clinicians in the management of HFrEF. Yet, many reports have shown significant care gaps in adherence to these recommendations in clinical practice, highlighting suboptimal use and/or dosing of evidence-based therapies. Adherence to guidelines has been shown to be associated with the best prognosis in HFrEF, with patients presenting with intolerances or contraindications having the highest risk of events; however, it remains unclear whether this association is causal or merely a marker of more advanced disease. Furthermore, individual characteristics may limit the possibility of reaching the targeted dosage of specific agents. Herein, we provide a comprehensive overview of clinicians' adherence to heart failure guidelines in a specialized real-life setting, particularly regarding use and optimization of guideline-derived medical therapies, as well as the implementation of more recent agents such as sacubitril/valsartan and SGLT2 inhibitors. We seek potential explanations for suboptimal treatment and its impact on patient outcomes.

The Pathophysiology and New Advancements in the Pharmacologic and Exercise-Based Management of Heart Failure With Reduced Ejection Fraction: A Narrative Review.

Heart failure with reduced ejection fraction (HFrEF) is a clinical syndrome whose management has significantly evolved based on the pathophysiology and disease process. It is widely prevalent, has a relatively high mortality rate, and is comparatively more common in men than women. In HFrEF, the series of maladaptive processes that occur lead to an inability of the muscle of the left ventricle to pump blood efficiently and effectively, causing cardiac dysfunction. The neurohormonal and hemodynamic adaptations play a significant role in the advancement of the disease and are critical to guiding the treatment and management of HFrEF. The first-line therapy, which includes loop diuretics, β-blockers, angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers, hydralazine/isosorbide-dinitrate, and mineralocorticoid receptor antagonists (MRAs), has been proven to provide symptomatic relief and decrease mortality and complications. The newly recommended drugs for guideline-based therapy, angiotensin receptor/neprilysin inhibitor (ARNI), sodium-glucose cotransporter 2 inhibitors, soluble guanylate cyclase, and myosin activators and modulators have also been shown to improve cardiac function, reverse cardiac remodeling, and reduce mortality rates. Recent studies have demonstrated that exercise-based therapy has resulted in an improved quality of life, exercise capacity, cardiac function, and decreased hospital readmission rates, but it has not had a considerable reduction in mortality rates. Combining multiple therapies alongside holistic advances such as exercise therapy may provide synergistic benefits, ultimately leading to improved outcomes for patients with HFrEF. Although first-line treatment, novel pharmacologic management, and exercise-based therapy have been shown to improve prognosis, the existing literature suggests a need for further studies evaluating the long-term effects of MRA and ARNI.

Personalized lifetime prediction of survival and treatment benefit in patients with heart failure with reduced ejection fraction: The LIFE-HF model.

Although trials have proven the group-level effectiveness of various therapies for heart failure with reduced ejection fraction (HFrEF), important differences in absolute effectiveness exist between individuals. We developed and validated the LIFEtime-perspective for Heart Failure (LIFE-HF) model for the prediction of individual (lifetime) risk and treatment benefit in patients with HFrEF. Cox proportional hazards functions with age as the time scale were developed in the PARADIGM-HF and ATMOSPHERE trials (n = 15 415). Outcomes were cardiovascular death, heart failure (HF) hospitalization or cardiovascular death, and non-cardiovascular mortality. Predictors were age, sex, New York Heart Association class, prior HF hospitalization, diabetes mellitus, extracardiac vascular disease, systolic blood pressure, left ventricular ejection fraction, N-terminal pro-B-type natriuretic peptide, and glomerular filtration rate. The functions were combined in life-tables to predict individual overall and HF hospitalization-free survival. External validation was performed in the SwedeHF registry, ASIAN-HF registry, and DAPA-HF trial (n = 51 286). Calibration of 2- to 10-year risk was adequate, and c-statistics were 0.65-0.74. An interactive tool was developed combining the model with hazard ratios from trials to allow estimation of an individual's (lifetime) risk and treatment benefit in clinical practice. Applying the tool to the development cohort, combined treatment with a mineralocorticoid receptor antagonist, sodium-glucose cotransporter 2 inhibitor, and angiotensin receptor-neprilysin inhibitor was estimated to afford a median of 2.5 (interquartile range [IQR] 1.7-3.7) and 3.7 (IQR 2.4-5.5) additional years of overall and HF hospitalization-free survival, respectively. The LIFE-HF model enables estimation of lifelong overall and HF hospitalization-free survival, and (lifetime) treatment benefit for individual patients with HFrEF. It could serve as a tool to improve the management of HFrEF by facilitating personalized medicine and shared decision-making.

Heart failure with reduced ejection fraction: clinical and economic burden and insights into current and emerging treatments.

Heart failure (HF) imposes a large and growing burden on the population, with a prevalence that is projected to increase to more than 8 million adults by 2030. The high risk of morbidity and mortality associated with HF is further exacerbated by the frequent presence of comorbidities. The coexistence of HF and comorbid conditions can result in emergency department visits and hospitalizations that not only affect patients and their families but also pose a growing economic burden on health care systems. The largest costs arise from hospitalization for HF, with outpatient care and associated medication costs comprising the second largest component. For patients with HF with reduced ejection fraction (HFrEF), defined as left ventricular ejection fraction of 40% or less, remarkable improvements in outcomes have been observed in recent decades due to the availability of disease-modifying therapies. However, the management of HFrEF remains suboptimal, with many patients either not receiving guideline-directed medical therapy (GDMT) or experiencing delays in receiving target doses. Since this can result in preventable hospitalizations and deaths, action is needed to ensure rapid initiation of GDMT. Optimal treatment can be hindered by such patient factors as the presence of comorbidities and socioeconomic barriers that include the cost of multiple treatments. Furthermore, poor treatment adherence is common among patients with HF. Measures aimed at tailoring therapies to individual patients and reducing medical costs are important to increase the uptake of and adherence to therapy and therefore improve clinicaloutcomes.

Chronic heart failure: the role of di vericiguat.

The introduction of multiple new pharmacological agents over the past three decades in the field of heart failure with reduced ejection fraction (HFrEF) has led to reduced rates of mortality and hospitalizations, and consequently, the prevalence of HFrEF has increased, and up to 10% of patients progress to more advanced stages, characterized by high rates of mortality and hospitalizations and poor quality of life. Vericiguat, a novel oral soluble guanylate cyclase stimulator, has proved effective in patients with HFrEF who had recently been hospitalized or had received intravenous diuretic therapy. In these patients, vericiguat reduced the primary outcome of death from cardiovascular causes or first hospitalization for heart failure in comparison with placebo. By reducing hospital admissions in a population at a very high risk of re-hospitalization, vericiguat might have a positive impact on healthcare costs for the management of HFrEF.

Advances in the Management of Heart Failure with Reduced Ejection Fraction; The Role of SGLT2is, ARNI, Myotropes, Vericiguat, and Anti-inflammatory Agents: A Mini-review.

Heart failure with reduced ejection fraction (HFrEF) has been associated with poor prognosis, reduced quality of life, and increased healthcare expenditure. Despite tremendous advances in HFrEF management, reduced survival and a high rate of hospitalization remain unsolved issues. Furthermore, HFrEF morbidity and economic burden are estimated to increase in the following years; hence, new therapies are constantly emerging. In the last few years, a series of landmark clinical trials have expanded our therapeutic armamentarium with a ground-breaking change in HFrEF-related outcomes. Sodium-glucose co-transporter 2 inhibitors (mainly dapagliflozin and empagliflozin) have already revolutionized the management of HFrEF patients via a significant reduction in cardiovascular mortality and heart failure hospitalizations. Furthermore, vericiguat and omecamtiv mecarbil have emerged as promising and novel disease-modifying therapies. The former restores the impaired cyclic guanosine monophosphate pathway, and the latter stimulates cardiac myosin without marked arrhythmogenesis. Both vericiguat and omecamtiv mecarbil have been shown to reduce heart failure admissions. Sacubitril/valsartan is an established and effective therapy in HFrEF patients and should be considered as a replacement for angiotensin-converting enzyme inhibitors (ACEi) or angiotensin II receptor blockers (ARBs). Lastly, inflammasome activity is implicated in HFrEF pathophysiology, and the role of anti-inflammatory agents in HFrEF trajectories is readily scrutinized, yet available therapies are ineffective. This mini-review summarizes the major and most recent studies in this field, thus covering the current advances in HFrEF therapeutics.

Management of Heart Failure with Reduced Ejection Fraction Globally and in Lebanon: Where Do SGLT-2is Stand?

Heart failure (HF) is a clinical syndrome due to structural and/or functional cardiac anomalies, accompanied by elevated natriuretic peptide levels and/or cardiogenic pulmonary or systemic congestion; severely compromising patients’ health, performance and quality of life. The advancement of novel treatment and their endorsement by international medical and scientific societies have shifted the treatment of HF with reduced ejection fraction (HFrEF) towards quadruple therapy: an angiotensin receptor-neprilysin inhibitor or an angiotensin-converting enzyme inhibitor, a beta-blocker, a mineralocorticoid receptor antagonist and a sodium/glucose co-transporter-2 inhibitor (SGLT2i). This paper reviews the available literature on state-of-the-art diagnostic and therapeutic advances in HFrEF, discusses landmark trials that shifted the paradigm towards quadruple therapy in HFrEF, visits the potential challenges in Lebanon and globally, proposes an algorithm for treatment introduction and sequencing in HFrEF and highlights clinical considerations for HFrEF management and patient education and follow-up. This practical guidance could serve cardiologists and other medical specialists in identifying clinical signs of HFrEF, diagnosing patients, referring them or prescribing the components of quadruple therapy, and offering medical advice and follow-up. We highlight the role of SGLT2is in HF management and their effectiveness in reducing rates of hospitalization for HF as well as cardiovascular deaths, with satisfactory safety profile.

Meta-Analysis on Drug and Device Therapy of New York Heart Association Functional Class IV Heart Failure With Reduced Ejection Fraction

Heart failure with reduced ejection fraction (HFrEF) is associated with significant morbidity and mortality, particularly in patients with New York Heart Association (NYHA) functional class IV symptoms. Decades of discovery have heralded significant advancements in the pharmacologic management of HFrEF. However, patients with NYHA IV symptoms remain an under-represented population in almost every clinical trial to date, leaving clinicians with limited evidence with which to guide drug treatment decisions in this patient group with severe heart failure. Randomized controlled trials of adult patients with NYHA IV symptoms of HFrEF randomized to current guideline-recommended medical therapy were included in this systematic review and meta-analysis. The outcomes of interest included the rate of all-cause mortality, cardiovascular mortality, and heart failure hospitalization. A total of 39 randomized controlled trials were included. A total of 6 studies examined angiotensin converting enzyme inhibitors, with meta-analyses of 2 demonstrating a reduced risk of all-cause mortality (relative risk (RR) 0.76, 95% confidence interval 0.59 to 0.97, p=0.03). A total of 11 studies examined β blockers, with meta-analysis of 6 demonstrating a reduced risk of all-cause mortality (risk ratio 0.74, 95% confidence interval 0.60 to 0.92, p=0.008). A study examined the mineralocorticoid antagonist spironolactone, reporting a reduced risk of all-cause mortality in the NYHA IV subgroup. A total of 6 studies examined device therapy, demonstrating the benefit of cardiac resynchronization therapy with or without an implantable cardiac defibrillator in reducing hospitalization in the NYHA IV subgroup. Although trial evidence exists for angiotensin converting enzyme inhibitors, β-blockers, and mineralocorticoid antagonist therapy in the NYHA IV population, the role of angiotensin receptor blockers is unclear. Ivabradine, angiotensin receptor neprilysin inhibitors, and sodium-glucose transport protein 2 inhibitors remain underinvestigated and have not been proved to provide any benefit above standard heart failure therapy in patients with HFrEF and NYHA IV symptoms.

Abstract 13725: The Dose Difference of Carvedilol for Heart Failure Management Between Asian-Americans and Japanese Could Show No Difference in the Improvement of Heart Function

Introduction: Carvedilol has improved cardiac mortality and morbidity for heart failure with reduced ejection fraction (HFrEF). The initial and target doses used in the Japanese randomized controlled trials (RCTs) were almost half of those in the USA leading to markedly lower recommended doses for HF management the in Japanese national guidelines compared to the USA. Hypothesis: Race may play a role in the optimal dose of carvedilol for HFrEF management. Methods: The international collaborative study was performed to compare the dose difference and the effect on heart functions, such as left ventricular EF (LVEF) and heart rate (HR), among Asian-Americans (AA), Caucasians (CA), and Japanese (JA) using real-world data. Each local ethics committee approved the study protocol at the University of California, San Diego (UCSD), the Osaka University Hospital (OUH), and the OU pharmaceutical sciences. The initial population at UCSD Health and OUH consisted of 1078 patients with HFrEF (≥ 20 years, EF<40%) treated with carvedilol (668 AA and CA and 410 JA). After inclusion/exclusion criteria, the study population consisted of 26 AA, 36 CA, and 96 JA. Results: Initial carvedilol dose (mg/day) (AA, 14.5 ± 11.9; CA, 19.1 ± 18.7; JA, 4.3 ± 4.2) and the dose at one year (30.9 ± 22.4; 34.5 ± 21.4; 11.2 ± 6.5) were significantly lower for JA compared to AA or CA ( p < 0.05 vs JA, respectively). AA had the highest frequency of carvedilol discontinuation (%; AA, 10.7; CA, 2.6; JA, 6.5) and dose reduction (18.4, 10.7, 2.2) ( p < 0.05, chi-square test). Clinical measurements of LVEF (%) measured before carvedilol initiation and after one year (before; 28.9 ± 8.8, 26.5 ± 8.0, 28.8 ± 7.4, after; 42.9 ± 11.1, 37.5 ± 15.3, 41.2 ± 13.1) and HR (beats/min) (before; 81.9 ± 19.0, 77.7 ± 13.5, 74.7 ± 10.9, after; 77.8 ± 10.6, 74.0 ± 12.5, 69.4 ± 9.4) showed no significant difference among the three groups. There were also no significant differences in event-free survival and in changes from baseline to 1 year in LVEF and HR, LVDd, or LVDs. Conclusions: JA patients exhibited similar effectiveness compared to AA and CA despite markedly lower carvedilol doses. Doses in AA were more similar to CA vs JA. Dose-deescalation may be an option in Asian HFrEF patients intolerable to high doses of carvedilol.

Guideline-based audit of the hospital management of heart failure with reduced ejection fraction.

Heart failure is a major burden in Australia in terms of morbidity, mortality and healthcare expenditure. Multiple evidence-based therapies are recommended for heart failure with reduced ejection fraction (HFrEF), but data on physician adherence to therapy guidelines are limited. To compare use of HFrEF therapies against current evidence-based guidelines in an Australian hospital inpatient population. A retrospective review of patients admitted with a principal diagnosis of HFrEF across six metropolitan hospitals in Sydney, Australia, between January 2015 and June 2016. Use of medical and device therapies was compared with guideline recommendations using individual patient indications/contraindications. Readmission and mortality data were collected for a 1-year period following the admission. Of the 1028 HFrEF patients identified, 39 were being managed with palliative intent, leaving 989 patients for the primary analysis. Use of beta-blockers (87.7% actual use/93.6% recommended use) and diuretics (88.4%/99.3%) was high among eligible patients. There were large evidence-practice gaps for angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers (ACEI/ARB; 66.4%/89.0%) and aldosterone antagonists (41.0%/77.1%). In absolute terms, use of these therapies each increased by over 11% from admission. Ivabradine (11.5%/21.2%), automated internal cardiac defibrillators (29.5%/66.1%) and cardiac resynchronisation therapy (13.1%/28.7%) were used in a minority of eligible patients. Over the 1-year follow-up period, the mortality rate was 14.8%, and 44.2% of patients were readmitted to hospital at least once. Hospitalisation is a key mechanism for initiation of HFrEF therapies. The large evidence-practice gaps for ACEI/ARB and aldosterone antagonists represent potential avenues for improved HFrEF management.

Use of a remote telemonitoring platform significantly improves medication optimisation in heart failure patients

Abstract Background Guideline directed medical therapy (GDMT) has been shown to reduce morbidity and mortality in patients with heart failure with reduced ejection fraction (HFrEF). Despite this, a large number of eligible patients do not receive these treatments or have prolonged delays in achieving optimal doses. Purpose To determine whether a telemonitoring-supported, remote medication optimisation programme could increase the proportion of HFrEF patients reaching maximum tolerated GDMT, in a shorter period of time compared to usual care. Methods A prospective, randomised controlled trial recruited 108 patients with a diagnosis of HFrEF from the ambulatory heart function clinic of a North American cardiac centre. All patients were enrolled onto a non-invasive remote monitoring platform which allowed daily nurse coordinator-led assessment of patient-reported symptoms and trends in heart rate, blood pressure and weight. In the remote titration intervention group, telemonitoring data were used by treating physicians to make decisions on optimisation of GDMT every two weeks, which was enacted by the patient's nurse coordinator, with no physician visit required. Patients in the control group were reviewed in clinic by their treating physician, where medication doses were optimised as per standard of care. The proportion of patients achieving maximum tolerated GDMT, and the time taken for this were compared between groups. Continuous data are presented as mean±standard deviation and compared with Student's t-test, while categorical data are shown as number (%) and compared using the Chi-squared test. Results 108 patients (69.4% male, mean age 54.1±15.4 years) were recruited with a median follow-up of 740 days. Baseline characteristics and medication prescription were similar between groups (56 randomised to remote titration, RT, 52 to usual care, UC, see Table). There were three withdrawals from the RT group and two from the UC group. Significantly more patients in the RT group 52/53 (98.1%) achieved the primary outcome, reaching maximum tolerated GDMT, compared with 42/50 (84.0%) in the UC group (p=0.01). The RT group achieved GDMT earlier (123±70 vs. 183±136 days, p=0.01) with a 40% reduction in clinic visits (p<0.01). In a time-to-event analysis, time to optimisation was significantly shorter in the intervention group (median 105 vs. 165 days, p[log rank] <0.01, see Figure). There was a similar increase in prescription of GDMT in both groups and no differences in hospitalisation or urgent clinic review suggesting that there was no excess hazard of remote titration. Conclusion Remote titration of GDMT in HFrEF patients resulted in more patients achieving maximum tolerated doses, on average two months earlier, with a reduction in clinic visits and no excess adverse outcomes. Telemonitoring-supported remote GDMT titration is effective, safe and could reduce healthcare costs associated with the management of HFrEF. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): DHB is supported by a post-doctoral fellowship award from TRANSFORM-HF (Ontario, Canada).

SGLT2i uptake among heart failure patients with reduced ejection fraction: ongoing prescriber hesitancy and how to address this

Abstract Background The evidence of mortality benefit from sodium-glucose transport protein 2 inhibitors (SGLT2i) in the management of heart failure with reduced ejection fraction (HFrEF) has been observed since 2019. Its first-line use in HFrEF, regardless of diabetes status, has been recommended by The European Society of Cardiology (ESC) since September 2021. Yet prescriber hesitancy surrounding SGLT2i use is still an under investigated issue resulting in centres falling short of gold-standard care. A simple review of pharmacotherapy pattern can alert clinicians to under prescribing of SGLT2i inhibitors and respond by improving adherence to guidelines. Purpose To describe the pharmacotherapy pattern of HFrEF patients attending an outpatient (Heart Failure Support Unit) HFSU in Ireland. Methods A retrospective analysis was performed in HFrEF patients actively attending the HFSU. Active attendance was considered a single engagement with the service between 1st January 2021 and 31st December 2021, and patients who have not died, been transferred to another service, or loss to follow-up. Information collected from digital records included patient demographic, comorbidities, baseline investigations, and pharmacotherapy pattern. Sensitivity analysis was performed for patients with type 2 diabetes (T2DM). Results 156 HFrEF patients were actively attending the HFSU. The mean age was 72.1 (±12.5) years and majority were male 114 (73.1%). The following pharmacotherapy pattern was revealed: angiotensin-converting enzyme inhibitors/ angiotensin II receptor blockers (ACEi/ARBs) 80 (51.3%), ARNi 55 (35.3%), β-blockers 142 (91.0%), mineralocorticoid receptor antagonist (MRA) 58 (37.2%), SGLT2i 9 (5.8%) and Ivabradine 9 (5.8%). Sensitivity analysis for T2DM patients (n=45) reveals a pattern of ACEi/ARBs 46.7%, ARNi 37.8%, β-blockers 95.6%, MRA 42.2%, SGLT2i 20.0% and Ivabradine 8.9%. All 9 instances of SGLT2i use were in T2DM patients. Since identification of SGLT2i under-prescribing, an interim review on 28th February 2022 revealed that total SGLT2i prescription had increased by 19 (211.1%), all of which were outside the T2DM population. Conclusions SGLT2i is still under prescribed for HFrEF management and prescriptions have the tendency to be restricted to T2DM patients. Identification of pharmacotherapy pattern can alert clinicians to prescriber hesitancy and increase new SGLT2i prescriptions outside the T2DM population. Funding Acknowledgement Type of funding sources: None.

Omecamtiv mecarbil for the management of heart failure: a meta-analysis of randomized controlled trials

Abstract Background Omecamtiv mecarbil (OM) is a selective cardiac myosin activator that promotes contractility in patients with Heart Failure with Reduced Ejection Fraction (HFrEF). We aimed to study the clinical outcomes of OM in this population. Methods PubMed, Cochrane CENTRAL Registry of Controlled Trials, and ClinicalTrials.gov were searched for randomized controlled trials (RCTs) that compared OM with placebo for the management of HFrEF. Efficacy and safety data were summarized with odds ratios (OR) and a 95% confidence interval (CI) using a fixed-effect model predicting low heterogeneity between studies. Results Four RCTs were included, totalizing 9,364 patients, 4,779 treated with OM and 4,585 with placebo. Mean age ranged from 63–66 years, 15–22% female, ejection fraction 26–29%, ischemic etiology 53–66%. Length of follow up ranged from 1 to 21 months. There was no difference in the outcomes all cause death (OR 0.99, 95% CI 0.9–1.1, p=0.91), cardiovascular death (OR 1.01, 95% CI 0.91–1.12, p=0.87) and heart failure events or hospitalizations (OR 0.96, 95% CI 0.87–1.05, p=0.35), Figure. Conclusion In a meta-analysis of 4 RCTs, OM showed no difference compared with placebo in the risk of all-cause death, cardiovascular death, or heart failure events among patients with HFrEF. Funding Acknowledgement Type of funding sources: None.

The design of the Dashboard Activated Services and Telehealth for Heart Failure (DASH-HF) study: A pragmatic quality improvement randomized implementation trial for patients with heart failure with reduced ejection fraction

BackgroundGaps in the receipt and dosing of guideline-directed medical therapy (GDMT) persist for patients with heart failure with reduced ejection fraction (HFrEF) [1]. In 2020, the Veterans Affairs (VA) developed a heart failure (HF) specific population dashboard to monitor care quality and performance on standard HFrEF performance measures [2]. MethodsThe Dashboard Activated Services and Telehealth for HF (DASH-HF) study is a pragmatic randomized quality improvement study designed to evaluate the utility of proactive population management clinics using the VA's HF dashboard to optimize GDMT for patients with HFrEF. Panel management telemedicine clinics incorporated multidisciplinary clinicians to perform chart review and impromptu telephone encounters to evaluate current HFrEF management and opportunities to optimize GDMT. The study will evaluate the efficacy of proactive panel management to usual care at 6 months as quantified by the GDMT optimization potential score. Secondary outcomes include hospitalizations, mortality, and clinician time per intervention. The study completed enrollment and randomization of 300 participants. The intervention was performed from September to December 2021. ConclusionDASH-HF will contribute to the literature by evaluating use of the existing VA dashboard to identify HF patients with the lowest adherence to GDMT and proactively target this group for the intervention.Registration:https://clinicaltrials.gov/. Unique identifier: NCT05001165.

Daily ambulatory remote monitoring system for drug escalation in chronic heart failure with reduced ejection fraction: pilot phase of DAVID-HF study.

Underutilization of guideline-directed heart failure with reduced ejection fraction (HFrEF) medications contributes to poor outcomes. A pilot study to evaluate the safety and efficacy of a home-based remote monitoring system for HFrEF management was performed. The system included wearable armband monitors paired with the smartphone application. An HFrEF medication titration algorithm was used to adjust medication daily. The primary endpoint was HFrEF medication utilization at 120 days. Twenty patients (60.5 ± 8.2 years, men: 85%) with HFrEF were recruited. All received angiotensin-converting enzyme inhibitor (ACEI)/angiotensin receptor blocker (ARB)/angiotensin receptor-neprilysin inhibitor (ARNI) at recruitment; 45% received ≥50% maximal targeted dose (MTD) with % MTD of 44.4 ± 31.7%. At baseline, 90 and 70% received beta-adrenergic blocker and mineralocorticoid receptor antagonist (MRA), 35% received ≥50% MTD beta-adrenergic blocker with % MTD of 34.1 ± 29.6%, and 25% received ≥50% MTD MRA with % MTD of 25.0 ± 19.9%. At 120 days, 70% received ≥50% MTD ACEI/ARB/ARNI (P = 0.110) with % MTD increased to 64.4 ± 33.5% (P = 0.060). The proportion receiving ≥50% MTD ARNI increased from 15 to 55% (P = 0.089) with % MTD ARNI increased from 20.6 ± 30.9 to 53.1 ± 39.5% (P = 0.006*). More patients received ≥50% MTD MRA (65 vs. 25%, P = 0.011*) with % MTD MRA increased from 25.0 ± 19.9 to 46.2 ± 28.8% (P = 0.009*). Ninety-five per cent of patients had reduced NT-proBNP with the percentage reduction of 26.7 ± 19.7%. Heart failure with reduced ejection fraction medication escalation with remote monitoring appeared feasible.

Rapid Sequencing of Foundational Treatment for HFrEF: The Innovative Proposal of John McMurray and Milton Packer

The treatment of heart failure with reduced ejection fraction (HFrEF) involves implementing preventive measures, delaying disease progression, relieving symptoms and, above all, prolonging survival. The effectiveness of the drug arsenal for the management of HFrEF has been well established by several randomized clinical trials and is based on 4 foundational pillars of treatment: (1) β-blockers; (2) renin-angiotensin system inhibitors, including angiotensin-converting enzyme inhibitors (ACEis), angiotensin receptor blockers (ARBs), and angiotensin receptor-neprilysin inhibitors (ARNIs); (3) sodium-glucose cotransporter 2 inhibitors (SGLT2is); and [...]

SGLT-2 Inhibitor Use in Heart Failure: A Review for Nurses.

Sodium-glucose cotransporter-2 (SGLT-2) inhibitors (empagliflozin, canagliflozin, dapagliflozin, and ertugliflozin) are a new class of heart failure medications that have previously been exclusively utilized in the management of type 2 diabetes mellitus (T2DM). The rationale for using SGLT-2 inhibitors in patients with heart failure has stemmed from recent landmark clinical trials in T2DM in which reductions in mortality and hospitalization for heart failure were first observed. On the basis of these robust outcomes, empagliflozin has further been evaluated in heart failure with reduced ejection fraction (HFrEF) and preserved ejection fraction and dapagliflozin solely in the management of HFrEF. While cardiovascular outcomes among each agent vary depending on the patient population, updates among both the American and European guidelines have included SGLT-2 inhibitors as pillars of therapy. The exact mechanisms for how SGLT-2 inhibitors are beneficial in heart failure are unknown, but current hypotheses include multiple metabolic and hemodynamic mechanisms. The purpose of this review is to summarize available literature focusing on the use of the SGLT-2 inhibitors as adjunctive therapy in heart failure, as well as evaluate mechanisms for heart failure benefit, adverse effects, and practical considerations for using these agents in the clinical setting.

Electrical management of heart failure: from pathophysiology to treatment.

Electrical disturbances, such as atrial fibrillation (AF), dyssynchrony, tachycardia, and premature ventricular contractions (PVCs), are present in most patients with heart failure (HF). While these disturbances may be the consequence of HF, increasing evidence suggests that they may also cause or aggravate HF. Animal studies show that longer-lasting left bundle branch block, tachycardia, AF, and PVCs lead to functional derangements at the organ, cellular, and molecular level. Conversely, electrical treatment may reverse or mitigate HF. Clinical studies have shown the superiority of atrial and pulmonary vein ablation for rhythm control and AV nodal ablation for rate control in AF patients when compared with medical treatment. Ablation of PVCs can also improve left ventricular function. Cardiac resynchronization therapy (CRT) is an established adjunct therapy currently undergoing several interesting innovations. The current guideline recommendations reflect the safety and efficacy of these ablation therapies and CRT, but currently, these therapies are heavily underutilized. This review focuses on the electrical treatment of HF with reduced ejection fraction (HFrEF). We believe that the team of specialists treating an HF patient should incorporate an electrophysiologist in order to achieve a more widespread use of electrical therapies in the management of HFrEF and should also include individual conditions of the patient, such as body size and gender in therapy fine-tuning.