Therapy For Heart Failure Patients Research Articles

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<0.001) were more prevalent in those with reduced compared to mildly-reduced LVEF. ACEI/ARB/ARNI and BBC were used by >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.

Features of treatment of transthyretin amyloid cardiomyopathy: clinical case

For several years, there has been a significant increase in the number of patients diagnosed with cardiac amyloidosis or amyloid cardiomyopathy (AC). The reason is the growing concern of specialists about amyloidosis and the increased accuracy of the instrumental methods of examination of patients of cardiological profile. Nowadays, more than 30 types of amyloidosis are known, however, the two main types are most commonly associated with cardiac involvement: amyloidosis of light chains (AL) and transthyretin amyloidosis (ATTR). Regardless of the underlying pathogenesis of amyloid production, cardiac involvement is the main cause of mortality in systemic amyloidosis. In addition to difficulties in early diagnosis, there are difficulties with further management of the disease. With the appearance of specific treatment, different depending on the type of amyloidosis, the problem of symptomatic therapy in these patients has become acute. Heart failure (HF) signs are usually prevalent in cardiac signs. Besides, patients with AC often have various arrhythmias and heart conduction disorders. However, the selection of heart failure therapy in patients with AC is complicated by the development of restrictive hemodynamic phenotype and concomitant autonomic dysfunction, making it impossible to manage standard heart failure therapy. The article presents a clinical case of a patient with a hereditary type of transthyretin amyloidosis with the cardiac involvement, whose main clinical manifestations were heart failure, cardiac rhythm and conductions disorders. This case demonstrates the importance of comprehensive and personalized approach in the management of ATTR-AC, the features of pathophysiology which require special approaches even to management of symptomatic therapy.

Role of ejection fraction in patients at risk for advanced heart failure: insights from the HELP-HF registry.

Patients with heart failure (HF) with reduced ejection fraction (EF) (HFrEF), mildly reduced EF (HFmrEF), and preserved EF (HFpEF) may all progress to advanced HF, but the impact of EF in the advanced setting is not well established. Our aim was to assess the prognostic impact of EF in patients with at least one 'I NEED HELP' marker for advanced HF. Patients with HF and at least one high-risk 'I NEED HELP' criterion from four centres were included in this analysis. Outcomes were assessed in patients with HFrEF (EF≤40%), HFmrEF (EF 41-49%), and HFpEF (EF≥50%) and with EF analysed as a continuous variable. The prognostic impact of medical therapy for HF in patients with EF<50% and EF>50% was also evaluated. All-cause death was the primary endpoint, and cardiovascular death was a secondary endpoint. Among 1149 patients enrolled [mean age 75.1±11.5years, 67.3% males, 67.6% hospitalized, median follow-up 260days (inter-quartile range 105-390days)], HFrEF, HFmrEF, and HFpEF were observed in 699 (60.8%), 122 (10.6%), and 328 (28.6%) patients, and 1year mortality was 28.3%, 26.2%, and 20.1, respectively (log-rank P=0.036). As compared with HFrEF patients, HFpEF patients had a lower risk of all-cause death [adjusted hazard ratio (HRadj ) 0.67, 95% confidence interval (CI) 0.48-0.94, P=0.022], whereas no difference was noted for HFmrEF patients. After multivariable adjustment, a lower risk of all-cause death (HRadj for 5% increase 0.94, 95% CI 0.89-0.99, P=0.017) and cardiovascular death (HRadj for 5% increase 0.94, 95% CI 0.88-1.00, P=0.049) was observed at higher EF values. Beta-blockers and renin-angiotensin system inhibitors or sacubitril/valsartan were associated with lower mortality in both EF<50% and EF≥50% groups. Among patients with HF and at least one 'I NEED HELP' marker for advanced HF, left ventricular EF is still of prognostic value.

A scoring evaluation for the practical introduction of guideline-directed medical therapy in heart failure patients.

The guideline-directed medical therapy (GDMT) has been recommended for heart failure (HF) with reduced ejection fraction (HFrEF) based on the accumulating clinical evidence. However, it is difficult to implement all the trial-proven medications for every patient in the real world. A simple GDMT score was created, according to the combination of GDMT drugs (renin-angiotensin system inhibitors, beta-blockers, mineralocorticoid receptor antagonists, and sodium-glucose transporter 2 inhibitors) administration and their dosage (0-9 points). Its impact on the prognosis of HF patients was investigated. Admitted HF patients [HFrEF and HF with mildly reduced ejection fraction (HFmrEF), n=1054] were retrospectively analysed (excluding those with in-hospital death and dialysis). A simple GDMT score ≥5, but not the number of medications, was significantly associated with a reduction of all-cause death, HF readmission, and composite outcome (HF readmission and all-cause death) (P<0.001). Subgroup analysis showed that almost all groups with a simple GDMT score of 5 or higher had a better prognosis. The developed simple GDMT score was associated with prognosis in HFrEF and HFmrEF patients. Even if all four drugs cannot be introduced for some reason, a regimen with a simple GDMT score ≥5 may lead to a prognosis in HF patients.

The effectiveness of cognitive-behavioral therapy for heart failure patients: a narrative review.

Heart failure (HF) remains a major cause of morbidity, mortality and healthcare costs, despite available treatments. Psychological issues such as depression, anxiety and poor self-care are prevalent in HF patients. Such issues adversely affect patients' daily lives and increase hospitalization and mortality rates; therefore, effective approaches to address these are needed. Cognitive-behavioral therapy (CBT) has been proposed as potentially useful for psychological comorbidities in HF patients, but its efficacy is not well-established. This narrative review aimed to summarize the evidence on the effectiveness of CBT for HF patients. A search was conducted using PubMed and Google Scholar for randomized controlled trials (RCTs) on CBT for HF patients. Ten studies (nine RCTs and one case study) were included in the review. CBT was found to be an effective intervention for managing depression, anxiety, low quality of life, and impaired social and physical functioning in HF patients. The results suggest that CBT can improve psychological well-being and enhance the benefits of rehabilitation programs. Face-to-face CBT appears to be superior to conventional therapy and can be implemented in cardiac rehabilitation settings. Further research is needed to evaluate the efficacy of internet-based CBT for cardiac patients and identify factors that promote treatment adherence.

Transcatheter Edge-to-Edge Repair in 5,000 Patients With Secondary Mitral Regurgitation: COAPT Post-Approval Study

BackgroundReal-world applicability of the COAPT (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation) randomized controlled trial (RCT) has been debated because of careful patient selection and the contrasting results of the MITRA-FR (Multicentre Study of Percutaneous Mitral Valve Repair MitraClip Device in Patients with Severe Secondary Mitral Regurgitation) RCT. ObjectivesThe COAPT-PAS (COAPT Post-Approval Study) was initiated to assess the safety and effectiveness of the MitraClip in patients with secondary mitral regurgitation (SMR). MethodsCOAPT-PAS is a prospective, single-arm, observational study of 5,000 consecutive patients with SMR treated with the MitraClip at 406 U.S. centers participating in the TVT (Transcatheter Valve Therapy) registry from 2019 to 2020. The 1-year outcomes from the COAPT-PAS full cohort and the COAPT-like and MITRA-FR–like subgroups who met RCT inclusion/exclusion criteria are reported. ResultsPatients in the COAPT-PAS had more comorbidities, more severe HF and functional limitations, and less guideline-directed medical therapy than those in the COAPT or MITRA-FR RCTs. Patients in the COAPT-PAS full cohort and the COAPT-like (n = 991) and MITRA-FR–like (n = 917) subgroups achieved a 97.7% MitraClip implant rate, a similar and durable reduction of mitral regurgitation to ≤2+ at 1 year (90.7%, 89.7%, and 86.6%, respectively), a large improvement in quality of life at 1 year (Kansas City Cardiomyopathy Questionnaire +29 COAPT-PAS, +27 COAPT-like, and +33 MITRA-FR–like), faster procedure times, similar or lower clinical event rates compared with the RCTs’ MitraClip arms, and lower clinical event rates than the RCTs’ guideline-directed medical therapy only arms. One-year heart failure hospitalizations was 18.9% in COAPT-PAS, 19.7% in COAPT-like compared with 24.9% in COAPT-RCT, and 28.7% in COAPT-PAS-MITRA-FR–like compared with 47.4% in MITRA-FR-RCT. ConclusionsThis large, contemporary, real-world study reinforces the safety and effectiveness of the MitraClip System in patients with SMR, including those who met the COAPT or MITRA-FR RCT inclusion/exclusion criteria and patients excluded from the RCTs.

One-year real-world outcomes for patients undergoing transcatheter mitral valve repair: the Gulf MTEER registry (GULF Mitral Transcatheter Edge to Edge Repair)

BackgroundSevere mitral regurgitation (MR) with left ventricular dysfunction portends worse outcomes. Over the course of the last two decades, transcatheter repair of the mitral valve offered an alternative therapeutic modality...

Changes in Left Ventricular Global Longitudinal Strain in Patients With Heart Failure and Secondary Mitral Regurgitation: The COAPT Trial.

Background Left ventricular (LV) global longitudinal strain (GLS) provides incremental prognostic information over LV ejection fraction in patients with heart failure (HF) and secondary mitral regurgitation. We examined the prognostic impact of LV GLS improvement in this population. Methods and Results The COAPT (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation) trial randomized symptomatic patients with HF with severe (3+/4+) mitral regurgitation to transcatheter edge-to-edge repair with the MitraClip device plus maximally tolerated guideline-directed medical therapy (GDMT) versus GDMT alone. LV GLS was measured at baseline and 6-month follow-up. The relationship between the improvement in LV GLS from baseline to 6 months and the composite of all-cause death or HF hospitalization between 6- and 24-month follow-up were assessed. Among 383 patients, 174 (45.4%) had improved LV GLS at 6-month follow-up (83/195 [42.6%] with transcatheter edge-to-edge repair+GDMT and 91/188 [48.4%] with GDMT alone; P=0.25). Improvement in LV GLS was strongly associated with reduced death or HF hospitalization between 6 and 24 months (P<0.009), with similar risk reduction in both treatment arms (Pinteraction=0.40). By multivariable analysis, LV GLS improvement at 6 months was independently associated with a lower risk of death or HF hospitalization (hazard ratio [HR], 0.55 [95% CI, 0.36-0.83]; P=0.009), death (HR, 0.48 [95% CI, 0.29-0.81]; P=0.006), and HF hospitalization (HR, 0.50 [95% CI, 0.31-0.81]; P=0.005) between 6 and 24 months. Conclusions Among patients with HF and severe mitral regurgitation in the COAPT trial, improvement in LV GLS at 6-month follow-up was associated with improved outcomes after both transcatheter edge-to-edge repair and GDMT alone between 6 and 24 months. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01626079.

Novel potassium binders to optimize RAASi therapy in heart failure: A systematic review and meta-analysis

AimsHyperkalemia often occurs among heart failure (HF) patients, particularly when treated with renin-angiotensin-aldosterone system inhibitors (RAASi). Even modest potassium levels variations raise the risk of mortality and prompt patients to discontinue disease-modifying treatment, as RAASi. Novel potassium binders (NPB), patiromer and sodium zirconium cyclosilicate, are effective in reducing potassium levels and are approved for the treatment of hyperkalemia in HF, but whether their use results in a real optimization of HF treatment remains to be seen. The aim of the present meta-analysis was to assess the efficacy of NPB on the optimization of RAASi therapy in HF patients. Methods and resultsPubMed, Web of Science and Clinicaltrial.gov were searched without restrictions from inception to 06 August 2022 to identify valuable articles. The studies that met the inclusion criteria were analyzed. The prespecified primary outcome was the optimization of RAASi therapy in HF patients, defined as the proportion of patients on RAASi at the end of follow-up. Secondary outcomes were hyperkalemia events, reduction in potassium levels, and adverse drugs reactions. Six studies with a total of 1390 patients were included. NPB improved RAASi therapy optimization in HF by 14% (95% CI: 4–26%), decreased hyperkalemia events by 29% (95% CI: 55–92%), and reduced potassium levels by 0.31 mEq/L (95% CI: 0.18–0.44) compared to placebo, maintaining a good safety profile. ConclusionNPB are effective in allowing RAASi therapy optimization in patients affected by HF, in reducing hyperkalemia events and potassium levels. Systematic Review registrationCRD42022351811 URL: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=351811

Safety and Efficacy of Traditional Heart Failure Therapies in Patients With Cardiac Amyloidosis and Heart Failure

Randomized controlled trials have demonstrated mortality benefits for several medication classes in patients with heart failure (HF), especially with reduced ejection fraction (EF). However, the benefit of these traditional HF therapies in patients with HF from cardiac amyloidosis is unclear. our study aimed to evaluate the safety and efficacy of traditional HF therapies in patients with cardiac amyloidosis and HF with reduced EF or HF with mid-range EF (HFmrEF). We conducted a single-center retrospective study. Patients were included if they were diagnosed with cardiac amyloidosis and HF with reduced EF or HF with mid-range EF between January 2012 and 2022. The primary outcomes of interest were medication use patterns (for β blockers [BB], angiotensin-converting enzyme inhibitors [ACEI], angiotensin receptor blockers [ARBs], angiotensin receptor neprilysin inhibitors [ARNI], and mineralocorticoid receptor antagonists [MRAs]); potential medication side effects (symptomatic bradycardia, fatigue, hypotension, lightheadedness, and syncope); hospitalization; and death. The associations of BB, ACEI/ARB/ARNI, and MRA use with clinical outcomes were evaluated using Kaplan-Meier and Cox proportional hazards regression. A total of 82 patients met study criteria. At time of cardiac amyloidosis diagnosis, 63.4% were on a BB, 51.2% were on an ACEI/ARB/ARNI, and 43.9% were on an MRA. At last follow-up, 51.2% were on a BB, 35.4% were on an ACEI/ARB/ARNI, and 43.9% were on an MRA. There were no statistically significant differences in rates of potential medication side effects in patients on the medication class compared with those who were not. There was no association with hospitalization or mortality for baseline or follow-up BB, ACEI/ARB/ARNI, or MRA use. In conclusion, BBs, ACEI/ARB/ARNIs, and MRAs may be safely used in this population. However, their use does not appear to improve mortality or hospitalization.

Clinical effects of cognitive behavioral therapy in heart failure patients: a meta-analysis of randomized controlled trials

BackgroundAbout 20–40% of people with Heart failure (HF) suffer from some depression, which is 4–5% greater than the overall population. This depression can lead to undesirable outcomes, including elevated mortality rate and frequent hospitalization.PurposeThe current study aims to evaluate the impact of cognitive behavioural therapy (CBT) on self-care and the symptoms of depression and anxiety in HF patients.MethodsWe searched PubMed, Web of Science (WOS), Scopus, and Cochrane Library till 15 October 2022. All relevant randomized controlled trials (RCTs) were included. The data were extracted and pooled using Review Manager software (RevMan 5.4). Continuous data were pooled as mean difference and 95% confidence interval (CI).ResultsOur search retrieved 1146 records, and 7 studies (611 patients) were finally included. We assessed the Beck Depression Inventory-II (BDI-II) as the primary outcome of the study. Hamilton Rating Scale for Depression (HRSD-17), Change in Beck Anxiety Inventory, Kansas City Cardiomyopathy Questionnaire (KCCQ), and Self-Care of Heart Failure Index (SCHFI) were also assessed as secondary outcomes. With CBT, BDI-II showed a significant reduction after 4 to 6 months follow-up (MD = -4.87, 95% CI: [-8.06; -1.69], P = 0.003) as well as 8 to 9 months follow-up (MD = -5.71, 95% CI: [-8.95; -2.46], P = 0.0006). But no significant difference was shown with 3 months follow-up (M.D=-4.34; 95%CI: [-10.70; 2.03], P = 0.18).ConclusionsCBT has long-term (4–9 months) significant favorable outcomes decreasing anxiety and depression compared to non-CBT groups. No significant short-term (less than 3 months) impact on HF patients’ self-care, depression, or anxiety were shown.

Abstract P2040: Pannexin 1 Activation Drives Neutrophil Recruitment In A Murine Model Of Non-ischemic Heart Failure Induced By Isoproterenol

Pannexin 1 (Panx1), a ubiquitously expressed ATP release membrane channel, has been shown to play a role in inflammation and blood pressure regulation. Panx1 channel function is inhibited by spironolactone, a frontline therapy for heart failure patients. Despite this, the function of Panx1 in cardiomyocytes and a possible role in heart failure has not yet been studied. To investigate if Panx1 is involved in the development of non-ischemic heart failure, we use an acute (14 day) model of adrenergic stimulation (isoproterenol) to induce non-ischemic heart failure in a novel mouse model we have generated with constitutive deletion of Panx1 in cardiomyocytes by crossing mice expressing loxP-flanked alleles of Panx1 to mice expressing Cre recombinase under the control of the cardiomyocyte specific MyHC6 promoter (Panx1 MyHC6-Cre ). Constitutive deletion of Panx1 in cardiomyocytes had no effect on heart function at baseline, but protected mice against isoproterenol-induced non-ischemic heart failure (15 mg/kg/day isoproterenol, i.p.). Panx1 MyHC6-Cre mice were protected from systolic and diastolic dysfunction and cardiac hypertrophy as measured by echocardiography and heart mass, respectively. Moreover, Panx1 MyHC6-Cre mice demonstrated decreased recruitment of immune cells (CD45 + ), particularly neutrophils (CD11b + , Ly6g + ) to the myocardium as measured by confocal microscopy and flow cytometry. In vitro , treatment of H9c2 rat myoblasts with isoproterenol led to Panx1-dependent release of ATP and Yo-Pro-1 uptake in a dose-dependent manner, as assessed by pharmacological blockade by spironolactone and siRNA-mediated knock-down of Panx1. These data demonstrate that that β-adrenergic stimulation in cardiomyocytes activates Panx1 channels and that Panx1 deficiency in cardiomyocytes protects against non-ischemic heart failure and the associated cardiac dysfunction at least in part by reducing immune cell recruitment. Taken together, our study provides evidence for Panx1 channel inhibition as a therapeutic approach to ameliorate cardiac dysfunction in heart failure patients.

Incidence, Predictors, and Outcomes Associated With Worsening Renal Function in Patients With Heart Failure and Secondary Mitral Regurgitation: The COAPT Trial.

Background The incidence and implications of worsening renal function (WRF) after mitral valve transcatheter edge-to-edge repair (TEER) in patients with heart failure (HF) are unknown. Therefore, the aim of this study was to determine the proportion of patients with HF and secondary mitral regurgitation who develop persistent WRF within 30 days following TEER, and whether this development portends a worse prognosis. Methods and Results In the COAPT (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation) trial, 614 patients with HF and severe secondary mitral regurgitation were randomized to TEER with the MitraClip plus guideline-directed medical therapy (GDMT) versus GDMT alone. WRF was defined as serum creatinine increase ≥1.5× or ≥0.3 mg/dL from baseline persisting to day 30 or requiring renal replacement therapy. All-cause death and HF hospitalization rates between 30 days and 2 years were compared in patients with and without WRF. WRF at 30 days was present in 11.3% of patients (9.7% in the TEER plus GDMT group and 13.1% in the GDMT alone group; P=0.23). WRF was associated with all-cause death (hazard ratio [HR], 1.98 [95% CI, 1.3-3.03]; P=0.001) but not HF hospitalization (HR, 1.47 [ 95% CI, 0.97-2.24]; P=0.07) between 30 days and 2 years. Compared with GDMT alone, TEER reduced both death and HF hospitalization consistently in patients with and without WRF (Pinteraction=0.53 and 0.57, respectively). Conclusions Among patients with HF and severe secondary mitral regurgitation, the incidence of WRF at 30 days was not increased after TEER compared with GDMT alone. WRF was associated with greater 2-year mortality but did not attenuate the treatment benefits of TEER in reducing death and HF hospitalization compared with GDMT alone. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01626079.

The Potential Role of Torsemide in Optimizing Loop Diuretic Therapy for Heart Failure Patients.

Heart failure is associated with an increased frequency of hospitalization, reduced life span, and greater risk to public health, thus posing a challenge. In India, torsemide is one of the commonly used loop diuretics for decongestion in heart failure. However, this use of torsemide, including its dosing, and up/down titration, is based on practical experience. Loop diuretic therapy for heart failure patients poses several dilemmas due to the lack of robust evidence based on which treatment decisions can be made. To guide physicians on the optimal use of torsemide in heart failure patients with or without renal impairment, a panel of expert cardiologists and nephrologists from India convened to develop this expert opinion document for the use of torsemide. This expert opinion on torsemide will pave the way for optimal management with loop diuretic therapy in real-world heart failure patients.

Initiation of Medical Therapy for Heart Failure Patients According to Kidney Function: A Danish Nationwide Study.

Use of medical therapies for heart failure (HF) patients with moderate kidney dysfunction is low. We hypothesized that lack of initiation of HF therapy reflects the clinicians' reluctance in very elderly and frail patients more than kidney dysfunction itself. HF patients were identified from nationwide registers between 2014 and 2021. Information was obtained on eGFR, frailty status, and prescription of HF therapy. Patients were divided into three groups: normal kidney function (eGFR ≥ 60); moderate kidney dysfunction (GFR between 30 and 59); and severe kidney dysfunction (GFR < 30). Multivariate Cox models were used to study the association of eGFR, age, and frailty with use of HF therapy. Of the 42,320 HF patients included those with lower eGFR were significantly older and frailer (median age 74.3 years and 37.8% frail). The crude initiation rate of all three drug classes decreased with decreasing eGFR in a stepwise fashion. After adjusting for age and frailty status, initiation of MRA decreased with decreasing kidney function (moderate kidney function HR 0.80(95% CI 0.77-0.84) and severe kidney function HR 0.24(0.21-0.27)). After adjusting for age and frailty status, initiation of RAS inhibitor and BB was not significantly lower for moderate kidney dysfunction (HR 0.97(0.93-1.02), and HR 1.06(0.97-1.16, respectively)). Initiation of RAS inhibitor was significantly lower for patients with severe kidney dysfunction, HR 0.45(0.41-0.50), but not for BB initiation HR 1.09(1.05-1.14). In a real-world HF cohort, patients with moderate and severe kidney dysfunction were associated with reduced use of MRA irrespective of age and frailty. Reduced use of RASi was associated with severe kidney dysfunction, whereas for patients with moderate kidney dysfunction, reduced use was mainly driven by aging and frailty. Reduced use of BB seemed to be primarily explained by aging and frailty.

Heart Failure Therapies following Acute Coronary Syndromes with Reduced Ejection Fraction: Data from the ACSIS Survey.

Guideline-directed medical therapies for heart failure (HF) may benefit patients with reduced left ventricular ejection fraction (LVEF) following acute coronary syndromes (ACS). Few real-world data are available regarding the early implementation of HF therapies in patients with ACS and reduced LVEF. 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 inhibitors (ARNI); (b) beta-blockers; (c) mineralocorticoid receptor antagonist (MRA) and (d) sodium-glucose cotransporter-2 inhibitors (SGLT2I). The 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. History of HF, anterior wall myocardial infarction and Killip class II-IV (32% vs. 14% p < 0.001) were more prevalent in those with reduced compared to mildly-reduced LVEF. ACEI/ARB/ARNI and beta-blockers were used by the majority 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 about 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. 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.