Therapy For Heart Failure Patients Research Articles

Intravenous Iron Therapy in Heart Failure Patients With Iron Deficiency: Benefits, Safety, and Guidelines.

Iron deficiency is a common comorbidity in heart failure (HF) patients, with up to 50% of ambulatory patients with HF affected. Intravenous (IV) iron therapy has emerged as a promising treatment approach for HF patients with concomitant iron deficiency. This review summarizes the current literature on the use of IV iron therapy in HF patients, focusing on its benefits in improving quality of life, and exercise capacity, and reducing HF hospitalizations. However, concerns about the long-term cardiotoxic effects of IV iron, including the risk of iron overload, are also addressed. The review highlights the importance of a balanced approach to iron replacement and provides an overview of the 2022 American College of Cardiology/American Heart Association guidelines, which recommend IV iron therapy for eligible patients. Additionally, the review underscores the need for further research, particularly in HF patients with preserved ejection fraction and acute HF. While IV iron therapy shows promise, questions about its safety and specific formulations remain to be fully addressed.

Effect of adaptive cardiac resynchronization therapy in heart failure patients with pacemaker dependency

Effect of adaptive cardiac resynchronization therapy in heart failure patients with pacemaker dependency

Prognostic Value of Standard Heart Failure Medication in Patients with Cardiac Transthyretin Amyloidosis.

Introduction: Cardiac transthyretin amyloidosis (ATTR) is a progressive, fatal disease leading to heart failure due to accumulation of amyloid fibrils in the interstitial space and may occur as a hereditary (ATTRv) or wild-type (ATTRwt) form. Guidelines recommend the use of ACE inhibitors (ACEis) and beta-blockers (BBs) as heart failure therapy (HFT) in all patients with symptomatic heart failure and reduced ejection fraction, independent of the underlying etiology. However, the prognostic benefit of ACEis and BBs in ATTR has not been elucidated in detail yet. We thus sought to retrospectively investigate the outcome of patients with ATTRwt or ATTRv under HFT. Methods: Medical records of 403 patients with cardiac ATTR (ATTRwt: n = 268, ATTRv: n = 135) were screened for long-term medication as well as clinical, laboratory, electrocardiographic and echocardiographic data. Patients were assessed between 2005 and 2020 at the University Hospital Heidelberg. Kaplan-Meier analysis was used to analyze potential differences in survival among different subgroups. Results: The mean follow-up was 28 months. In total, 43 patients (32%) with ATTRv and 140 patients (52%) with ATTRwt received HFT. Survival was significantly shorter in patients receiving HFT in ATTRv (46 vs. 83 months, p = 0.0007) vs. non-HFT. A significantly better survival was observed in patients with comorbidities (coronary artery disease, arterial hypertension) and HFT among ATTRwt patients (p = 0.004). No significant differences in survival were observed in the other subgroups. Conclusions: Survival analysis revealed a potential benefit of HFT in patients with ATTRwt and cardiac comorbidities such as coronary artery disease and/or arterial hypertension. In contrast, HFT should be used with caution in patients with ATTRv.

The Effect of Using a Remote Patient Management Platform in Optimizing Guideline-Directed Medical Therapy in Heart Failure Patients: A Randomized Controlled Trial

BackgroundGuideline-directed medical therapy (GDMT) remains underutilized in patients with heart failure with reduced ejection fraction, leading to morbidity and mortality. ObjectivesThe Medly Titrate (Use of Telemonitoring to Facilitate Heart Failure Mediation Titration) study was an open-label, randomized controlled trial to determine whether remote medication titration for patients with heart failure with reduced ejection fraction was more effective than usual care (UC). MethodsIn this study, 108 patients were randomized to remote GDMT titration through the Medly heart failure program (n = 56) vs UC (n = 52). The primary outcome was the proportion of patients completing GDMT titration at 6 months. Secondary outcomes included the number of clinic visits and time required to achieve titration, patient health outcomes, and health care utilization, including urgent clinic/emergency department visits and hospitalization. ResultsAt 6 months, GDMT titration was completed in 82.1% (95% CI: 71.2%-90.8%) of patients in the intervention arm vs 53.8% in UC (95% CI: 41.1%-67.7%; P = 0.001). Remote titration required fewer in-person (1.62 ± 1.09 vs 2.42 ± 1.65; P = 0.004) and virtual clinic visits (0.50 ± 1.08 vs 1.29 ± 1.86; P = 0.009) to complete titration. Median time to optimization was shorter with remote titration (3.42 months [Q1-Q3: 2.99-4.04 months] vs 5.47 months [Q1-Q3: 4.14-7.33 months]; P < 0.001). The number of urgent clinic/emergency department visits (incidence rate ratio of remote vs control groups: 0.90 [95% CI: 0.53-1.56]; P = 0.70) were similar between groups, with a reduction in all-cause hospitalization with remote titration (incidence rate ratio: 0.55 [95% CI: 0.31-0.97]; P = 0.042). ConclusionsRemote titration of GDMT in heart failure with reduced ejection fraction was effective, safe, feasible, and increased the proportion of patients achieving target doses, in a shorter period of time with no excess adverse events compared with UC. (Use of Telemonitoring to Facilitate Heart Failure Mediation Titration [Medly Titrate]; NCT04205513)

Long-term cost-effectiveness of transcatheter mitral valve repair in HF patients with secondary mitral regurgitation.

The long-term cost-effectiveness of MitraClip in heart failure patients with secondary mitral regurgitation is still unclear. This study aimed to evaluate the long-term cost-effectiveness of MitraClip added to guideline-directed medical therapy vs. guideline-directed medical therapy alone in heart failure patients with secondary mitral regurgitation from the perspective of the healthcare systems of mainland China, the United Kingdom, Germany, and the United States. A two-stage (decision+Markov) model was built. Health utilities were defined by the New York Heart Association class, heart failure re-hospitalization, and death and were calculated based on the 5year follow-up results of the Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation trial. Direct healthcare costs were derived from the nationally representative data. Future utilities and costs were discounted at country-specific rates. The primary outcome was the lifetime incremental cost-effectiveness ratio. The mean age of the base case in our model was 72.2years. Over a lifetime horizon, treatment with MitraClip was associated with 829 fewer heart failure re-hospitalizations per 1000 treated patients. The MitraClip treatment was associated with incremental quality-adjusted life-year gains of 0.71, 0.76, 0.78, and 0.78, as well as incremental cost-effectiveness ratios of ¥468462, £28910, €26045, and $71199 per quality-adjusted life-year for a lifetime horizon in mainland China, the United Kingdom, Germany, and the United States, respectively. In probabilistic sensitivity analysis, 0.2%, 59.4%, 99.6%, and 84.7% of patients were cost-effective in mainland China, the United Kingdom, Germany, and the United States at the country-specific willingness-to-pay thresholds. MitraClip+guideline-directed medical therapy was cost-effective in heart failure patients with secondary mitral regurgitation in the United Kingdom, Germany, and the United States, but not in mainland China from the perspective of the national healthcare system.

Incremental diagnostic and prognostic utility of left atrial deformation in heart failure using speckle tracking echocardiography.

Left atrium (LA) is a very important component of cardiovascular performance. The assessment of LA function has gathered the interest with expanding research supporting the utility as a biomarker for outcomes in heart failure (HF). Echocardiography is the main imaging modality which helps in a qualitative and quantitative assessment of the LA size and function. Recent advances in probe technology and software analysis have provided a better understanding of LA anatomy, physiology, pathology, and function. A variety of parameters have been defined as markers of LA function but there is no single parameter that best defines LA function. Speckle tracking echocardiography-derived analysis of LA deformation provides a window on all phases of LA function (reservoir, conduit, and booster pump). There is accumulative published data that supported the diagnostic and prognostic values of LA deformation integration during echo assessment of LA in HF. This review article summarized the clinical utility of LA deformation that may help in prediction, diagnosis, categorization, risk stratification, and guiding the proper selection of therapy in HF patients in daily practice.

Advancements in MitraClip Intervention for Mitral Regurgitation: A Comprehensive Review and Comparative Analysis of Clinical Trials.

This comprehensive review explores the evolution and clinical impact of MitraClip intervention in the management of mitral regurgitation. Mitral regurgitation results from dysfunction in the mitral valve (MV) apparatus. The MitraClip Clip Delivery System was approved by the Food and Drug Administration (FDA) in 2013. The discussion delves into the procedural foundation of MitraClip intervention, primarily based on Alfieri's technique of edge-to-edge leaflet approximation. As highlighted by key clinical trials, includingEndovascular Valve Edge-to-Edge Repair(EVEREST) II Trial, Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation (COAPT) Trial, and Percutaneous Repair with the MitraClip Device for Severe Functional/Secondary Mitral Regurgitation (MITRA-FR) trial, the efficacy and safety of MitraClip were evaluated in comparison to surgical interventions and guideline-directed medical therapy. Notably, the COAPT demonstrated significant benefits in reducing all-cause mortality and heart failure hospitalization, while the MITRA-FR presented contrasting results, emphasizing the importance of patient selection. An analysis of the EVEREST II trial underscores MitraClip's potential to achieve comparable outcomes to surgical intervention, emphasizing its role in reducing mitral regurgitation and improving clinical status. However, limitations and complications, such as device-related issues and the potential impact on future MV surgery, are discussed. The study also explores the evolving landscape of MV interventions, reflecting advancements and the growing acceptance of MitraClip. In conclusion, the MitraClip device represents a significant advancement in the treatment of mitral regurgitation. The data presented highlights its promising results in terms of reduced hospitalization rates, improved in-hospital mortality, and enhanced quality of life for patients. However, challenges remain, and careful consideration of patient selection and underlying pathology is crucial in determining the optimal treatment approach. Ongoing research and clinical experience will continue to refine our understanding of MitraClip's role in the evolving landscape of MV interventions.

Cardiac contractility modulation in patients with heart failure - A review of the literature.

Experimental in vivo and in vitro studies showed that electric currents applied during the absolute refractory period can modulate cardiac contractility. In preclinical studies, cardiac contractility modulation (CCM) was found to improve calcium handling, reverse the foetal myocyte gene programming associated with heart failure (HF), and facilitate reverse remodeling. Randomized control trials and observational studies have provided evidence about the safety and efficacy of CCM in patients with HF. Clinically, CCM therapy is indicated to improve the 6-min hall walk, quality of life, and functional status of HF patients who remain symptomatic despite guideline-directed medical treatment without an indication for cardiac resynchronization therapy (CRT) and have a left ventricular ejection fraction (LVEF) ranging from 25 to 45%. Although there are promising results about the role of CCM in HF patients with preserved LVEF (HFpEF), further studies are needed to elucidate the role of CCM therapy in this population. Late gadolinium enhancement (LGE) assessment before CCM implantation has been proposed for guiding the lead placement. Furthermore, the optimal duration of CCM application needs further investigation. This review aims to present the existing evidence regarding the role of CCM therapy in HF patients and identify gaps and challenges that require further studies.

An Insidious Comorbidity: Depression and Chronic Heart Failure

Depression and heart failure (HF) are in a close bilateral relationship: the appearance of one is potentiated by the other entity and the effects on the outcome are amplified within this ”dangerous liaison”. Depression is present in about one in five HF patients and is severe in almost half of them. The risk factors for depression in HF are female gender, elderly, the severity of HF symptoms, a history of isolated systolic hypertension or coronary heart disease (CHD), previous hospitalization and previous depressive episodes. Depression in HF patients increases medication non-adherence, is associated with poor outcomes after heart transplantation and is predictive of events and mortality in cardiac resynchronization therapy (CRT). The current assumptions related to the physiopathological mechanisms include a common genetic polymorphisms, inflammation, generalized immune system disturbance, disturbances of platelet function, increased catecholamine levels, deamination of monoamines linked with monoamine oxidase activity, a dysregulation of the autonomic nervous system, increased serotonin levels, ischemia, life-style and medication non-compliance, a poor familial support and social isolation. Assessment of cognitive functioning should be part of routine clinical examination in HF, the diagnosis of depression is based on questionnaires (e.g. Patient Health Questionnaire-2 - PHQ-2) and on clinical interview. There is still no consensus on the best therapy for HF patients with depression (non-pharmacological and pharmacological therapies) but, for sure, depression in HF is harder to treat.

P 036: The effects of intravenous iron therapy in heart failure patients with iron deficiency in Hospital University Sains Malaysia

P 036: The effects of intravenous iron therapy in heart failure patients with iron deficiency in Hospital University Sains Malaysia

Guideline-directed medical therapy in heart failure patients with reduced ejection fraction in Palestine: Retrospective clinical audit study

ObjectivesTo assess the characteristics of patients with heart failure with reduced ejection fraction (HFrEF) and heart failure with mid-range ejection fraction (HFmrEF), as well as the current application of guideline-directed medical therapy (GDMT) in Palestine. MethodsThis retrospective cohort study involved a population of heart failure (HF) patients who visited cardiology clinics at An-Najah National University Hospital and the National Hospital, Palestine. The primary outcome measures of interest were the proportions of patients prescribed guideline-based cardiovascular medications (GBCMs), such as angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin II receptor blockers (ARBs), β-blockers, and mineralocorticoid receptor antagonists (MRAs), and the corresponding optimized doses at ≥ 50 % of targets and the reasons underlying the non-prescription of GDMT. ResultsA total of 70.5%, 56.6%, and 88.6% of patients were on ACEIs/ARBs, MRAs, and β-blockers, respectively. Of all patients, 38.7% were on the triple GDMT regimen. ConclusionLess than half the patients received the triple combination treatment. Age, diabetes mellitus, chronic renal disease, and admission to the hospital for HF all had significant independent relationships with the reduced utilization and inadequate dosage of GDMT.

Remote Monitoring Titration Clinic To Implement Guideline-directed Medical Therapy For Heart Failure Patients With Reduced Ejection Fraction: A Pilot Intervention Study

Remote Monitoring Titration Clinic To Implement Guideline-directed Medical Therapy For Heart Failure Patients With Reduced Ejection Fraction: A Pilot Intervention Study

Relationship between serum iron level and physical function in heart failure patients is lost by presence of diabetes.

Iron deficiency (ID) is common in patients with heart failure (HF) and is reportedly associated with exercise intolerance and impaired quality of life. Iron supplementation therapy in HF patients with ID improves exercise capacity. Conversely, protective roles of iron depletion in the development of diabetes mellitus (DM) and its complications have been proposed. This study aimed to determine the impact of ID on physical function in HF patients with and without DM. We enrolled consecutive patients who were admitted to our institute for HF diagnosis and management. The short physical performance battery (SPPB) was used to evaluate physical function, and low physical function was defined as an SPPB score of <10 points as individuals with SPPB scores of <10 points are most likely to be classified as frail and are at high risk for disability and future adverse events, including death. ID was defined as serum ferritin<100 or 100-299ng/mL when transferrin saturation (TSAT) was <20% according to the HF guidelines. Among the 562 HF patients (72±14years old; 56% male), 329 patients (58%) and 191 patients (34%) had ID and low physical function, respectively. Multivariate logistic regression analysis showed that TSAT as a continuous variable, but not ID, was a predictor of low physical function (odds ratio: 0.980, P=0.024). Subgroup analysis showed that a significant association between low TSAT and low physical function was lost in HF patients with DM (P for interaction<0.001). A spline dose-response curve for the relationship between TSAT and risk of low physical function with adjustments for covariates associated with low physical function in non-DM patients was almost linear with an increase in the risk of low physical function as the TSAT increased, but such a relationship was not found in the analyses of DM patients. A lack of close TSAT-SPPB relationship in HF patients with DM was confirmed also in a propensity-score-matched cohort. TSAT as a continuous variable, but not ID, was independently associated with physical function in HF patients, and a significant association was lost in patients with HF and DM, suggesting a limited impact of iron supplementation therapy in HF patients with DM.

Regurgitant volume to LA volume ratio in patients with secondary MR: the COAPT trial.

The conceptual framework of proportionate vs. disproportionate mitral regurgitation (MR) translates poorly to individual patients with heart failure (HF) and secondary MR. A novel index, the ratio of MR severity to left atrial volume (LAV), may identify patients with 'disproportionate' MR and a higher risk of events. The objectives, therefore, were to investigate the prognostic impact of MR severity to LAV ratio on outcomes among HF patients with severe secondary MR randomized to transcatheter edge-to-edge repair (TEER) with the MitraClip™ device plus guideline-directed medical therapy (GDMT) vs. GDMT alone in the COAPT trial. The ratio of pre-procedural regurgitant volume (RVol) to LAV was calculated from baseline transthoracic echocardiograms. The primary endpoint was 2-year covariate-adjusted rate of HF hospitalization (HFH). Among 567 patients, the median RVol/LAV was 0.67 (interquartile range 0.48-0.91). In patients randomized to GDMT alone, lower RVol/LAV was independently associated with an increased 2-year risk of HFH (adjHR: 1.77; 95% CI: 1.20-2.63). RVol/LAV was a stronger predictor of adverse outcomes than RVol or LAV alone. Treatment with TEER plus GDMT compared with GDMT alone was associated with lower 2-year rates of HFH both in patients with low and high RVol/LAV (Pinteraction = 0.28). Baseline RVol/LAV ratio was unrelated to 2-year mortality, health status, or functional capacity in either treatment group. Low RVol/LAV ratio was an independent predictor of 2-year HFH in HF patients with severe MR treated with GDMT alone in the COAPT trial. TEER improved outcomes regardless of baseline RVol/LAV ratio. Trial Name: Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation (The COAPT Trial) (COAPT) ClinicalTrial.gov Identifier NCT01626079URL https://clinicaltrials.gov/ct2/show/NCT01626079.

Developing an AI-based decision engine for disease-modifying therapy in heart failure – A pilot study

Abstract Aim Heart failure is an escalating burden on global health care systems. Modernizing heart failure care is inevitable, with eHealth products poised to play an important role. However, eHealth devices that can initiate and adjust heart failure medication are currently lacking. Consequently, this study aimed to develop an artificial intelligence-based decision engine to provide guideline-based recommendations for disease-modifying medication in heart failure patients. Methods and Results We developed the decision engine by converting the ESC heart failure guidelines into Business Process Model and Notation, a visual modeling language suitable for developing complex decision engines. A safety evaluation, based on clinical parameters, was conducted to ascertain the system’s applicability to specific cases. The decision engine renders specific decisions concerning disease- modifying therapy for heart failure patients. We defined 72 virtual heart failure patient scenarios, encompassing a broad spectrum of baseline characteristics and background medication. All recommendations offered by the engine were evaluated by an independent heart failure specialist. All but three recommendations (94%) were identical to the treatment decisions by the heart failure specialist and all (100%) were in line with the 2021 ESC heart failure guidelines. Conclusion The decision engine offers guideline-based recommendations for disease-modifying therapy, positioning it as a tool to enhance self-care among heart failure patients. To validate our results, the decision engine is being prospectively tested in real-world patients in a multicenter clinical trial (NCT04699253).

Evidence-based heart failure therapies at discharge of patients with acute coronary syndromes and reduced ejection fraction: Data from the ACSIS survey

Abstract Background Guideline-directed medical therapies for heart failure (HF) may benefit patients with reduced left ventricular ejection fraction (LVEF) following acute coronary syndromes (ACS), even in the absence of overt HF. Few real-world data are available regarding early implementation of HF therapies in patients with ACS and reduced LVEF. Methods Data collected from the 2021 nationwide, prospective ACS Israeli Survey (ACSIS). Drug classes included: (a) angiotensin-converting enzyme inhibitors (ACEI), angiotensin receptor blockers (ARB) or angiotensin receptor-neprilysin inhibitor (ARNI); (b) beta-blockers; (c) mineralocorticoid receptor antagonist (MRA) and (d) sodium-glucose cotransporter-2 inhibitors (SGLT2I). Utilization of HF therapies at discharge or 90-days following ACS was analyzed in relation to LVEF [reduced ≤40% (n=406) or mildly-reduced 41-49% (n=255)] and short-term adverse outcomes. Results History of HF, anterior wall myocardial infarction and Killip class II-IV (32% vs. 14% p&amp;lt;0.001) were more prevalent in those with reduced compared to mildly-reduced LVEF. ACEI/ARB/ARNI and BBC were used by &amp;gt;85% of patients in both LVEF groups, though ARNI was prescribed to only 3.9% (LVEF≤40%). MRA was used by 42.9% and 12.2% of patients with LVEF ≤40% and 41-49%, respectively, and SGLT2I in a quarter of both LVEF groups. Overall, ≥3 HF drug classes were documented in 44% of the patients. A trend towards higher rates of 90-day HF rehospitalizations, recurrent ACS or all-cause death was noted in those with reduced (7.6%) vs. mildly-reduced (3.7%) LVEF, p=0.084. No association was observed between the number of HF drug classes, or the use of ARNI and/or SGLT2I with adverse clinical outcomes. Conclusions In current clinical practice, the majority of patients with reduced and mildly-reduced LVEF are treated by ACEI/ARB and beta-blockers early following ACS, whereas MRA is underutilized and the adoption of SGLT2I and ARNI is low. A greater number of therapeutic classes was not associated with reduced short-term rehospitalizations or mortality.Drug therapies for heart failure

Virtual Multi-disciplinary Team (vMDT) platform improves workflows and productivity within the heart failure pathway for patients in the UK National Health Service (NHS)

Abstract Background We implemented a virtual MDT platform as a technical solution to assist a heart failure MDT. vMDT would enable the team to document discussions and create actions for individual team members that were visible and transparent and thus ensuring rapid completion relating to patient care plans. Patients cases processed via this pathway in comparison to traditional approaches were able to access treatment optimisation and newer heart failure therapies more rapidly. Data from the vMDT platform helped plan for wider transformation. Purpose Integrating care between general practice (GP), community and hospital specialists is the current focus for the National Health Service (NHS) in the UK. An integrated approach necessitated better communication and sharing of information between MDTs. We decided that it was necessary to have the digital infrastructure to deliver this approach. Method The vMDT system harnessed information relevant to the patients heart failure and presented it to MDT members to view and contribute to the patients treatment plan, before, during and after a scheduled MDT meeting. Following the meeting the platform would instantly communicate actions to members of the professional team, ensuring transparency and rapid completion of actions. Processes were simplified, meaning that patients could be referred onwards at the click of a button. The patients could be referred into this pathway by a GP when patients continued to have symptoms. Pathway was made available to GP clinics covering a 200,000 patient population. Led by the commissioning transformation team, who managed the project alongside the GP cardiovascular lead, community heart failure nurse lead, and Hospital heart failure specialist nurse leads. Clinical pharmacists linked to the GP clinics were included and were the ones who would prepare, upload and present the heart failure cases. Results 98% (150 processed over 10 months) of patients referred along this pathway could be managed effectively. 5% would otherwise have been lost to follow up. 100% of actions created through this pathway were completed. 62% had their treatment optimised. Clinician satisfaction improved. Conclusion Virtual MDTs are the rave but there needs to be digital infrastructure to support this novel way of working, especially if we are to scale this up. A digital platform needs to have the safeguards for information security but also needs to align to an improved workflow for the health professionals working within the service. In future we would like to look at whether addition of decision support can further improve productivity and outcomes relating to optimisation of therapy for heart failure patients.

Abstract 14525: Mapping Disparities in Use of Guideline-Directed Medical Therapies for Heart Failure Patients With Reduced Ejection Fraction

Introduction: Current guidelines recommend simultaneous or rapid sequence initiation of multidrug guideline-directed medical therapy (GDMT) classes for heart failure with reduced ejection fraction (HFrEF). Despite this, well documented gaps in implementation exist; however, little is known regarding geographic disparities at the county level. Methods: A cohort study was conducted using Medicare claims (2013-2019). Patients from the study cohort were assigned to counties based on their residential ZIP codes. County level triple therapy use- defined as simultaneous prescription fills for beta blockers, renin-angiotensin system inhibitors (RASi), and mineralocorticoid receptor antagonists (MRAs), within 90 days of a medical encounter where HF was recorded- were calculated as %s. Features of counties including area-level indicators of poverty, employment, and educational attainment and aggregated patient-level sociodemographic and medical history variables were compared by quintiles of triple therapy use. Results: 304,857 patients from 2,600 counties were included. The median (interquartile range [IQR]) for three drug therapy use was 14.3% (10.3%-18.8%) across included counties with a wide variation (range: 0% to 54.5%). Counties in the lowest quintile of triple therapy use were concentrated in the South. Compared to counties in the highest use quintile, counties in lowest triple therapy use quintile had worse area-level indicators of socioeconomic status and were more frequently rural. Among patient-level sociodemographic factors, counties in lowest quintile had higher proportion of Blacks and patients with low-income subsidy. Conclusion and Relevance: Simultaneous use of three GDMT classes was infrequent in patients with HFrEF and a marked variation across counties was observed correlating with indicators of socioeconomic disadvantage. Addressing implementation gaps in GDMT use is a pressing need that requires urgent attention.

Long-term effects of angiotensin receptor neprilysin inhibitor therapy in heart failure patients with reduced ejection fraction: A retrospective cohort study.

Heart failure is an increasing public health issue with substantial morbidity and mortality rates. This study aimed to evaluate the efficacy, safety, and long-term outcomes of angiotensin receptor neprilysin inhibitor (ARNi) in the treatment of heart failure with reduced ejection fraction (HFrEF) 5 years after treatment initiation. This retrospective study analyzed a cohort of 75 patients diagnosed with HFrEF over a period of 5 years after the initiation of ARNi therapy. The initial clinical condition, laboratory and echocardiographic measurements including left ventricular ejection fraction (LVEF), New York Heart Association functional classes (NYHA-FC) and the prognostic nutritional index were compared to the corresponding values obtained after a 5-year period of ARNi therapy. In addition, the number of annual hospitalizations, mortality rates and any history of adverse effects during the follow-up period were recorded. The N-terminal pro-brain natriuretic peptide (NT-proBNP) level, LVEF, and NYHA-FC values demonstrated significant improvement at the end of the 5-year follow-up period (all parameters, P < .001). Although the observed increase in the prognostic nutritional index was not statistically significant (P = .077), it is worth noting. A significant reduction in daily diuretic doses and hospitalizations due to heart failure was observed following the use of ARNi (all comparisons, P < .001). The prevalence of hypotension was around 16% (being symptomatic in 4%), making it the most frequently observed adverse event. The 5-year cardiovascular mortality rate was 17.3%. The use of ARNi in HFrEF patients was associated with a notable improvement in NYHA-FC, LVEF, and NT-proBNP levels in the long-term, while also leading to a better nutritional status and reduced need for diuretics and annual hospitalization. Additionally, ARNi usage has been associated with improved nutritional status, decreased reliance on diuretics, and reduced frequency of annual hospitalizations. These effects were associated with a lack of significant increase in adverse effects. These results may contribute to a better understanding of ARNi's long-term effects on patient outcomes.

TNF-α protects from exacerbated myocarditis and cardiac death by suppressing expansion of activated heart-reactive CD4+ T cells.

Tumour necrosis factor α (TNF-α) represents a classical pro-inflammatory cytokine, and its increased levels positively correlate with the severity of many cardiovascular diseases. Surprisingly, some heart failure patients receiving high doses of anti-TNF-α antibodies showed serious health worsening. This work aimed to examine the role of TNF-α signalling on the development and progression of myocarditis and heart-specific autoimmunity. Mice with genetic deletion of TNF-α (Tnf+/- and Tnf-/-) and littermate controls (Tnf+/+) were used to study myocarditis in the inducible and the transgenic T cell receptor (TCRM) models. Tnf+/- and Tnf-/- mice immunized with α-myosin heavy chain peptide (αMyHC) showed reduced myocarditis incidence, but the susceptible animals developed extensive inflammation in the heart. In the TCRM model, defective TNF-α production was associated with increased mortality at a young age due to cardiomyopathy and cardiac fibrosis. We could confirm that TNF-α as well as the secretome of antigen-activated heart-reactive effector CD4+ T (Teff) cells effectively activated the adhesive properties of cardiac microvascular endothelial cells (cMVECs). Our data suggested that TNF-α produced by endothelial in addition to Teff cells promoted leucocyte adhesion to activated cMVECs. Analysis of CD4+ T lymphocytes from both models of myocarditis showed a strongly increased fraction of Teff cells in hearts, spleens, and in the blood of Tnf+/- and Tnf-/- mice. Indeed, antigen-activated Tnf-/- Teff cells showed prolonged long-term survival and TNF-α cytokine-induced cell death of heart-reactive Teff. TNF-α signalling promotes myocarditis development by activating cardiac endothelial cells. However, in the case of established disease, TNF-α protects from exacerbating cardiac inflammation by inducing activation-induced cell death of heart-reactive Teff. These data might explain the lack of success of standard anti-TNF-α therapy in heart failure patients and open perspectives for T cell-targeted approaches.