Search Results (81)

Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous syndrome with increasing prevalence and substantial morbidity and mortality. Recent advances in pharmacotherapy have transformed its management. This review summarizes current evidence supporting the use of sodium–glucose cotransporter 2 inhibitors, non-steroidal mineralocorticoid receptor antagonists, and glucagon-like peptide-1 receptor agonists, alongside selected use of angiotensin receptor–neprilysin inhibitors. Emphasis is placed on early initiation of disease-modifying therapies, phenotypic tailoring, and comorbidity-targeted strategies, especially in obese and diabetic patients. Together, these approaches define a new era of guideline-directed, personalized care for patients with HFpEF. Full article

Background/Objectives: Guidelines recommend patients with heart failure with reduced ejection fraction (HFrEF) receive four-pillar heart failure (4P-HF) therapy, which significantly reduces cardiac morbidity and mortality. However, implementing these guidelines effectively into clinical practice remains challenging. Methods: Patients with HFrEF on submaximal 4P-HF therapy were identified from a large, multicentre Cardiology network database using a natural language processing tool, supported by manual file review. A nurse-led, remotely delivered, medication uptitration program aimed to optimise therapy in this real-world cohort. Results: The final cohort included 2004 patients with a mean age of 72.7 ± 11.6 years. Utilisation of 4P-HF increased from 11.1% at baseline to 49.8% post intervention, and each individual medication class increased significantly post intervention (all p < 0.001). The largest increase was observed with the use of sodium–glucose cotransporter 2 inhibitors, which rose from 17.3% to 73.9%, followed by mineralocorticoid receptor antagonists (51.6% to 65.7%), beta-blockers (88.4% to 97.0%), and angiotensin-converting enzyme inhibitors/angiotensin receptor blockers/angiotensin receptor blocker–neprilysin inhibitors (89.8% to 96.4%). In patients on submaximal therapy, barriers were documented in all cases. Following medication optimisation, left ventricular ejection function (LVEF) improved significantly (38.5% ± 10.8% vs. 42.5% ± 11.7, p < 0.001). Conclusions: This nurse-led, remotely delivered, medication optimisation program significantly improved the adoption of 4P-HF therapy and LVEF in patients with HFrEF. The program demonstrates a practical, scalable solution for the optimisation of HFrEF therapy across a large healthcare network. Full article

Background/Objectives: Contextual memory associated with methamphetamine (METH) use contributes to relapse and persistence of addiction. Angiotensin II type 1 receptor (AT1R) signaling has been implicated in drug reinforcement. LCZ696, a clinically used combination of sacubitril (a neprilysin inhibitor) and valsartan (an AT1R antagonist), may interfere with METH-associated memory through the modulation of dopaminergic pathways. Methods: Male C57BL/6J mice were tested in a conditioned place preference (CPP) paradigm to assess the effects of LCZ696, sacubitril (AHU377), and valsartan on METH-induced memory expression and reinstatement. Synaptic plasticity in the nucleus accumbens (NAc) was examined by assessing the levels of synaptophysin (Syp) and postsynaptic density protein 95 (Psd95), as well as dendritic spine density. Dopaminergic signaling in the ventral tegmental area (VTA) was evaluated via ELISA, Western blotting, and chromatin immunoprecipitation (ChIP), targeting cAMP response element-binding protein (Creb) binding to the tyrosine hydroxylase (Th) promoter. To further assess the role of Th, an adeno-associated virus (AAV9) carrying a CRISPR-Cas9-based sgRNA targeting Th (AAV9-Th-sgRNA) was microinjected into the VTA. Results: LCZ696 and valsartan significantly reduced METH-induced CPP and reinstatement. LCZ696 reversed METH-induced synaptic and dopaminergic alterations and suppressed Creb-mediated Th transcription. Th knockdown attenuated both CPP acquisition and relapse. Conclusions: LCZ696 disrupts METH-associated contextual memory by modulating dopaminergic signaling and Creb-dependent Th expression, supporting its potential as a treatment for METH use disorder. Full article

Introduction: Cardiac involvement in patients with systemic sclerosis (SSc) can present variably from being asymptomatic to manifesting with heart failure, conduction abnormalities, pulmonary hypertension, and pericardial effusion. Symptomatic cardiac involvement portends a poor prognosis and worse overall survival. Sacubitril/valsartan (SV), an angiotensin receptor neprilysin inhibitor, has been shown to significantly reduce hospitalization rates and morbidity in patients with heart failure with reduced ejection fraction (HFrEF). This study aimed to investigate the effects of SV treatment in patients with SSc and heart failure. Methods: A retrospective analysis of patients with SSc was conducted using an electronic data capture tool. Patients with SSc treated with SV between January 2015 and August 2023 were identified. Comprehensive clinical phenotyping and longitudinal data analysis were performed to characterize the sub-type of patients and evaluate clinical outcomes, including hospitalizations and mortality, laboratory markers, and echocardiographic findings. Results: Twenty-four patients with SSc were treated with SV for a mean duration of 20.6 months. HFrEF was the primary indication for SV use in 91% of patients, primarily due to non-ischemic cardiomyopathy (87.5%). There was a significant reduction in systolic blood pressure from 128 mmHg to 114 mmHg (p < 0.001) and NT-proBNP levels from 15,130 pg/mL to 5082 pg/mL (p = 0.046). In the 19 patients with baseline and follow-up echocardiograms, there was a significant improvement in LVEF from 40.3% to 47.7% (p = 0.014). Hypotension was a common side effect leading to discontinuation of SV (n = 4, 16.7%). Serum creatinine had trends of improvement (1.9 mg/dL to 1.3 mg/d), though it did not reach statistical significance (p = 0.057). Conclusions: This study showed that SV effectively improved cardiac symptoms and function in patients with SSc presenting with HFrEF. Further prospective studies are needed to confirm these findings and explore the role of SV in the treatment of other manifestations of SSc. Full article

Cardiovascular diseases and cancer are the two primary causes of mortality worldwide. Although traditionally regarded as distinct pathologies, they share numerous pathophysiological mechanisms and risk factors, including chronic inflammation, insulin resistance, obesity, and metabolic dysregulation. Notably, several cancers have been identified as closely linked to cardiovascular diseases, including lung, breast, prostate, and colorectal cancers, as well as hematological malignancies, such as leukemia and lymphoma. Additionally, renal and pancreatic cancers exhibit a significant association with cardiovascular complications, partly due to shared risk factors and the cardiotoxic effects of cancer therapies. Addressing the overlapping risk factors through lifestyle modifications—such as regular physical activity, a balanced diet, and cessation of smoking and alcohol—has proven effective in reducing both CV and oncological morbidity and mortality. Furthermore, even in patients with established cancer, structured interventions targeting physical activity, nutritional optimization, and smoking cessation have been associated with improved outcomes. Beyond lifestyle modifications, pharmacological strategies play a crucial role in the prevention of both diseases. Several cardiovascular medications, including statins, aspirin, beta-blockers, and metformin, exhibit pleiotropic effects that extend beyond their primary indications, demonstrating potential anti-neoplastic properties in preclinical and observational studies. Recently, novel therapeutic agents have garnered attention for their possible cardioprotective and metabolic benefits. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and sodium-glucose cotransporter-2 inhibitors (SGLT2is), initially developed for managing type 2 diabetes, have shown CV and renal protective effects, alongside emerging evidence of their role in modulating cancer-related metabolic pathways. Inclisiran, a small interfering RNA targeting PCSK9, effectively lowers LDL cholesterol and may contribute to reducing CV risk, with potential implications for tumor biology. Additionally, sacubitril/valsartan, an angiotensin receptor–neprilysin inhibitor, has revolutionized heart failure management by improving hemodynamic parameters and exerting anti-inflammatory effects that may have broader implications for chronic disease prevention. Given the intricate interplay between CVD and cancer, further research is essential to clarify the exact mechanisms linking these conditions and assessing the potential of CV therapies in cancer prevention. This review aims to examine shared risk factors, consider the role of pharmacological and lifestyle interventions, and emphasize crucial epidemiological and mechanistic insights into the intersection of CV and oncological health. Full article

Background/Objectives: Cardiac resynchronization therapy (CRT) and angiotensin receptor–neprilysin inhibitors (ARNIs) are cornerstone therapies for patients with heart failure with reduced ejection fraction (HFrEF). However, nearly 30% of patients show no significant response to CRT alone. The potential of ARNI to enhance CRT outcomes—especially in non-responders—is an emerging field of interest. The objective of this review is to systematically evaluate and synthesize the available evidence on the clinical outcomes of combining CRT with ARNI therapy in patients with HFrEF. Methods: We conducted a comprehensive search of PubMed, Scopus, and Google Scholar up to September 2024, using the keywords “CRT and ARNI” and “cardiac resynchronization therapy and sacubitril/valsartan”. We included retrospective and prospective clinical studies, observational studies, and review articles reporting on patients with HFrEF treated with both CRT and ARNI. Studies not in English, animal studies, and those without full-text availability were excluded. Study selection and data extraction were performed in duplicate by independent reviewers, using PRISMA guidelines for transparency. The final selection included 8 studies published in the last four years, summarized by design, population, outcomes, and statistical significance. Results: The reviewed studies suggest that ARNI therapy, when combined with CRT, may contribute to improvements in left ventricle ejection fraction (LVEF), NYHA functional class, and ventricular remodeling, particularly in CRT non-responders. Some studies also report a potential reduction in ventricular arrhythmias and implantable cardioverter-defibrillator (ICD) interventions. However, outcomes varied across subgroups, and the influence of ARNI timing relative to CRT implantation remains inconclusive. Limitations: Heterogeneity in study designs and small sample sizes in some included studies limited the ability to conduct a meta-analysis. This review is not registered. Conclusions: ARNI therapy shows promise in enhancing CRT response in patients with HFrEF, particularly in non-responders. Further large-scale, prospective studies are needed to clarify optimal patient selection and treatment sequencing. Full article

Background: Current guidelines emphasize the importance of initiating or optimizing the four pillars of heart failure with reduced ejection fraction (HFrEF) therapy—beta-blockers (BB), mineralocorticoid receptor antagonists (MRA), angiotensin receptor–neprilysin inhibitors (ARNI), and sodium–glucose cotransporter-2 inhibitors (SGLT2i)—during hospitalization for acute decompensation. This study compares clinical characteristics and outcomes in HFrEF patients hospitalized for decompensated heart failure based on whether they were newly initiated on or were already receiving at least one of these four pillars. Methods: This prospective observational study included 203 HFrEF patients hospitalized for acute decompensation. Patients were divided into two groups: Group A (n = 126), not receiving any of the four pillars prior to admission, and Group B (n = 77), receiving at least one. Clinical and biological parameters were evaluated during hospitalization, with outcomes including changes in weight, blood pressure, heart rate, renal function (serum creatinine), electrolyte levels (sodium, potassium), and 30-day mortality. Statistical analyses included the non-parametric Mann–Whitney test and Chi-squared test. Results: Baseline characteristics (age, gender, LVEF, NT-proBNP) were similar between the two groups. No significant difference was observed in 30-day mortality (Group A: 7.14%, Group B: 5.55%, p = 0.74). Both groups experienced significant improvements in systolic and diastolic blood pressure and heart rate during hospitalization (p < 0.05). While serum creatinine levels remained stable in both groups, creatinine dynamics (Δcreatinine) were significantly different (p = 0.02), with Group B exhibiting a higher increase. The improvement in ejection fraction was more pronounced in Group A (p = 0.057) compared to Group B. Both groups demonstrated significant improvements in NYHA functional class (p < 0.001). In Group B, the use of MRAs and SGLT2 inhibitors significantly increased during hospitalization (p = 0.01 and p < 0.001, respectively). Conclusions: The initiation or optimization of the four pillars of HFrEF therapy during hospitalization for acute decompensation is feasible and well-tolerated. Early intervention leads to improvements in clinical parameters and functional status, supporting guideline recommendations for in-hospital initiation or optimization of HFrEF therapy. Special consideration should be given to renal function when optimizing therapy. Full article

Background/Objectives: Heart transplantation (HTX) is the definitive treatment for advanced heart failure (AdHF). The angiotensin receptor neprilysin inhibitor (ARNI) sacubitril/valsartan (S/V) has been shown to reduce heart failure (HF) hospitalizations and mortality when compared to conventionally administered HF medications (i.e. angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs)). Nevertheless, limited data are available on the hemodynamic (HD) effects of ARNI in patients with AdHF. Therefore, the aim of the present study was to compare echocardiographic, laboratory, and HD parameters relevant to HF before and after switching to ARNI in patients with AdHF awaiting HTX. Methods: A retrospective analysis was conducted utilizing available data on HD parameters, N-terminal pro-brain natriuretic peptide (NT-proBNP) levels, data on kidney function, HF therapy, and comorbidities. The study cohort comprised 13 AdHF patients (3 women, 10 men; mean age 56.4 ± 9 years) of whom 53.8% presented with non-ischemic and 46.2% with ischemic etiology. All patients were awaiting heart transplantation (HTX) and were transitioned to ARNI therapy between 2018 and 2021. Results: After switching to ARNI, we observed significant improvements: in left ventricular ejection fraction (LVEF: 27.27 ± 1.04% vs. 23.65 ± 1.02%, p = 0.03; data are given as mean ± SEM after vs. before ARNI therapy, respectively), cardiac output (CO: 4.90 ± 0.35 L/min vs. 3.83 ± 0.24 L/min, p = 0.013), and stroke volume (SV: 70.9 ± 5.9 mL vs. 55.5 ± 4.12 mL, p = 0.013). Significant reductions in systemic vascular resistance (SVR: 1188 ± 79.8 vs. 1600 ± 100 DS/cm⁵, p = 0.004) and pulmonary vascular resistance (PVR: 232.5 ± 34.8 vs. 278.9 ± 31.7 DS/cm⁵, p = 0.04) were also noted. Central venous pressure (CVP), pulmonary arterial systolic and diastolic pressures (PAPs and PAPd), pulmonary capillary wedge pressure (PCWP), and NT-proBNP levels did not exhibit significant changes upon ARNI administration. Conclusions: Early transition to ARNI therapy offers significant benefits for invasively measured hemodynamic parameters in patients with AdHF, potentially aiding in the stabilization and improvement of this vulnerable patient population. Full article

Introduction: Sacubitril/valsartan is an angiotensin receptor–neprilysin inhibitor (ARNI) drug used to treat patients with heart failure and has shown improvement in outcomes. Different studies reported the use of an ARNI in patients using left ventricular assist devices (LVADs). However, there are limited data on the use of ARNIs in this population. We aimed to assess the efficacy of ARNIs in LVAD patients. Methods: A systematic search was performed in PubMed, Scopus, Web of Science, Embase, and Cochrane from inception to November 2024. We used all relevant words for “ARNI” and “LVAD” to search, and we included studies that assessed ARNIs in patients with LVAD. Efficacy and safety outcomes were extracted from the included studies. R software version 4.4.2 was used for a meta-analysis. Results: Seven studies totaling 249 patients were included. The ARNI was found to be effective in improvements from baseline in the New York Heart Association (NYHA), B-type natriuretic peptide (BNP) (mean = −630.07 pg/mL, 95% CI [−1113.13, −147.01]), diuretic dose (furosemide equivalents) (mean= −76.05 mg/day, 95% CI [−145.11, −6.99]), left ventricular end-diastolic diameter (LVEED) (mean = −7.3 mm, 95% CI [−11.4, −3.1]), and left ventricular ejection fraction (LVEF) (mean =5, 95% CI [3.52, 6.48]). No improvement was found in the creatinine (Cr) level. However, a slight increase in the potassium level was noticed (mean= 0.17 mEq/L, 95% CI [0.02, 0.34]). The overall mortality in patients using the ARNI was 5%, 95% CI [0.00, 20], and discontinuation was found in 25%, 95% CI [0, 100]. Conclusions: The ARNI improved several cardiac structural and hemodynamic parameters in patients on LVAD support. Full article

Background: The wearable cardioverter defibrillator (WCD) has emerged as a valuable tool used for temporary protection from sudden cardiac death. However, since the WCD uses surface electrodes to detect arrhythmias, it is susceptible to inappropriate detection. Although shock conversion rates for the WCD are reported to be high for detected events, its efficacy in clinical practice tends to be degraded by patient noncompliance. Reasons for this include wearer discomfort and frequent false alarms, which may interrupt sleep and generate anxiety. Up to now, data on the incidence of false alarms emitted by the WCD and their predictors are rare. Objectives: The aim of our study was to assess the relationship between both artifact sensing and episode misclassification burden and wearing compliance in patients with a WCD (ZOLL LifeVest™ 4000 system, ZOLL CMS GmbH, Cologne, Germany). Methods and Results: We conducted a single-center retrospective observational study, analyzing patients with a WCD prescribed at our institution. A total of 134 patients (mean age 51.7 ± 13.8 years, 79.1% male) were included. Arrhythmia recordings were analyzed and categorized as non-sustained ventricular tachycardia, sustained ventricular tachycardia or fibrillation, artifact sensing or misclassified episodes. Indication for WCD prescription was both primary and secondary prophylaxis. A total of 3019 false WCD alarms were documented in 78 patients (average number of false alarms 38.7 ± 169.5 episodes per patient) over a mean WCD wearing time of 71.5 ± 70.9 days (daily WCD wearing time 20.2 ± 5.0 h). In a total of 78 patients (58.2% of the study population), either artifact sensing (76.9%), misclassified episodes (6.4%), or both (16.7%) occurred. Misclassified episodes included sinus tachycardias, atrial flutter, atrial fibrillation, premature ventricular contractions (PVCs), and intermittent bundle branch block. A multiple linear regression identified loop diuretics (regression coefficient [B] −0.11; 95% CI −0.21–(−0.0001); p = 0.049), angiotensin receptor–neprilysin inhibitors (ARNIs) (B −0.11; 95% CI 0.22–(−0.01); p = 0.033), and a higher R-amplitude of the WCD baseline electrocardiogram (ECG) (B −0.17; 95% CI −0.27–(−0.07); p = 0.001) as independent predictors for a lower number of artifact episodes per day. In addition, atrial fibrillation (B 0.05; 95% CI 0.01–0.08; p = 0.010), and calcium antagonists (B 0.07; 95% CI 0.02–0.12; p = 0.012) were independent predictors for increased numbers of misclassified episodes per day, while beta-blockers seemed to reduce them (B −0.06; 95% CI −0.10–(−0.01); p = 0.013). Patients terminated 61.0% of all false alarms manually by pressing the response button on average 1.9 times per false alarm with overall 3.6 manual terminations per affected patient per month. Conclusions: In conclusion, false alarms from the ZOLL LifeVest™ system were frequent, with artifact sensing being the most common cause. Hence, the occurrence of false alarms represents a significant side effect of WCD therapy, and efforts should be made to minimize false alarms. Full article

Background/Objectives: Angiotensin receptor neprilysin inhibitor (ARNI) and sodium-glucose co-transporter 2 inhibitors (SGLT2i) are essential medications in heart failure (HF) therapy, and their potential antiarrhythmic effects have been reported. Recently, ARNI and SGLT2i use for HF in adult congenital heart disease (ACHD) has been studied. However, whether any beneficial effects may be achieved on the arrhythmic burden in the complex population of ACHD with a systemic right ventricle (sRV) is still to be determined. Methods: We retrospectively collected all significant arrhythmic events from a cohort of patients with a failing sRV attending our tertiary care center on optimal guideline-directed medical therapy (GDMT) with ARNI and/or SGLT2i. Results: A total of 46 patients (mean age 38.2 ± 10.7 years, 58% male) on sacubitril/valsartan were included. Twenty-three (50%) patients were also started on dapagliflozin. After a median follow-up of 36 [Q1–Q3: 34–38] months, arrhythmic events occurred globally in 13 (28%) patients. Survival analysis showed significant reduction of clinically relevant atrial and ventricular arrhythmia at follow-up (p = 0.027). Conclusions: Our findings suggest that GDMT including sacubitril/valsartan and dapagliflozin may also offer an antiarrhythmic effect in ACHD patients with a failing sRV, by reducing the incidence of arrhythmic events at follow-up. Full article

Background/Objectives: Despite significant advances in the management of heart failure with reduced ejection fraction (HFrEF), data concerning older patients remain limited. The purpose of this study was to evaluate the implementation of guideline-directed medical therapy (GDMT) in older patients with HFrEF along with cardiac events and variation in clinical and echocardiographic parameters during follow-up in a heart failure (HF) clinic. Methods: We conducted a retrospective observational analysis of patients with HFrEF aged ≥ 80 years who attended an HF clinic between March 2022 and February 2023. The primary outcome was a composite of the first episode of worsening HF or cardiovascular death. All-cause death was also recorded. Results: We included 110 patients (30.9% females; mean age 82.9 years). After a median follow-up of 25.5 months, left ventricular ejection fraction (LVEF) improved (mean difference 12.5% (p < 0.001)). New York Heart Association class improved in 37% of patients, and N-terminal pro-B-type natriuretic peptide levels decreased (3091 (158–53354) to 1802 (145–19509), p < 0.001). The primary outcome occurred in 34 patients (30.9%). Patients without the primary outcome were more likely to receive sodium-glucose co-transporter-2 inhibitors (SGLT2i) (23.5% versus 67.1%, p < 0.001) and angiotensin receptor-neprilysin inhibitors, angiotensin-converting enzyme inhibitors, or angiotensin-receptor blockers (67.6% versus 84.2%, p < 0.05). These patients also received a greater number of GDMT medications (2 (0–4) versus 3 (1–4), p < 0.01) and demonstrated a higher LVEF at the last visit (41.2 ± 10.2% versus 47.1 ± 9.4%, p < 0.05). Survival analysis demonstrated a significant association between LVEF recovery (hazard ratio (HR) 0.35, p < 0.01), treatment with two or more GDMT medications (HR 0.29, p < 0.01), vasodilator use (HR 0.36, p < 0.01), and SGLT2i prescription (HR 0.17, p < 0.001) and a reduced risk of the primary endpoint. Conclusions: The optimization of HF treatment is achievable in older patients and may be associated with a reduction in cardiac events. Full article

Pulmonary hypertension (PH) associated with heart failure with preserved ejection fraction (PH-HFpEF) represents a frequent form of PH related to left ventricular dysfunction. The pathophysiology of PH-HFpEF is intricate, and varied and includes vascular, cardiac, and pulmonary factors that contribute synergistically to developing this clinical syndrome. Improved knowledge of the pathophysiology of PH-HFpEF has paved the way for the use of new drugs such as angiotensin receptor neprilysin inhibitors (ARNIs), non-steroidal mineral corticoid receptor antagonist (nsMRA), sodium-glucose cotransporter inhibitors (SGLT2is), levosimendan, and glucagon-like peptide 1 (GLP-1) agonists. ARNIs are a widely used drug for the treatment of PH associated with heart failure with reduced ejection fraction. They have also recently been used in PH-HFpEF patients with hemodynamic benefits that need to be confirmed in future research. Finerenone is an innovative non-steroidal mineralocorticoid receptor antagonist that exhibits notable cardioprotective and renoprotective properties in individuals suffering from chronic diabetic kidney disease. It also enhances outcomes for patients with heart failure, whether they have mildly reduced or preserved ejection fraction. Moreover, in experimental studies, finerenone has been found to lower pulmonary artery pressure, reduce muscularization, and decrease the wall thickness of pulmonary arteries. SGLT2i have revolutionized the treatment of patients with heart failure irrespective of left ventricular ejection fraction, and their treatment is also associated with an improvement in the hemodynamics profile in patients with PH-HFpEF. Levosimendan is a widely used inodilator in the treatment of acute and advanced heart failure. In addition, its use in patients with PH-HFpEF (supported by the positive effects on pulmonary hemodynamics that levosimendan exerts) has recently demonstrated hemodynamic benefit in a small phase 2 study that paved the way for phase 3 studies and the creation of an oral formulation of levosimendan. Finally, GLP1 agonists are a class of drugs that, in preliminary evidence, have shown a positive effect on cardiac hemodynamics, mainly by facilitating left ventricular unloading. These effects, along with the reduction in insulin resistance and weight loss, likely lead to beneficial outcomes for PH-HFpEF patients, especially those with obesity as a comorbidity. Full article

A dominant event determining the course of heart failure (HF) includes the disruption of the delicate sodium (Na⁺) and water balance leading to (Na⁺) and water retention and edema formation. Although incomplete decongestion adversely affects outcomes, it is unknown whether interventions directly targeting (Na⁺), such as strict dietary (Na⁺) restriction, intravenous hypertonic saline, and diuretics, reverse this effect. As a result, it is imperative to implement (Na⁺)-targeting interventions in selected HF patients with established congestion on top of quadruple therapy with angiotensin receptor neprilysin inhibitor, β-adrenergic receptor blocker, mineralocorticoid receptor antagonist, and sodium glucose cotransporter 2 inhibitor, which dramatically improves outcomes. The limited effectiveness of (Na⁺)-targeting treatments may be partly due to the fact that the current metrics of HF severity have a limited capacity of foreseeing and averting episodes of congestion and guiding (Na⁺)-targeting treatments, which often leads to dysnatremias, adversely affecting outcomes. Recent evidence suggests that spot urinary sodium measurements may be used as a guide to monitor (Na⁺)-targeting interventions both in chronic and acute HF. Further, the classical (2)-compartment model of (Na⁺) storage has been displaced by the (3)-compartment model emphasizing the non-osmotic accumulation of (Na⁺), chiefly in the skin. 23(Na⁺) magnetic resonance imaging (MRI) enables the accurate and reliable quantification of tissue (Na⁺). Another promising approach enabling tissue (Na⁺) monitoring is based on wearable devices employing ion-selective electrodes for electrolyte detection, including (Na⁺) and (Cl^–). Undoubtably, further studies using 23(Na⁺)-MRI technology and wearable sensors are required to learn more about the clinical significance of tissue (Na⁺) storage and (Na⁺)-related mechanisms of morbidity and mortality in HF. Full article

Cardiovascular complications are the major cause of diabetes mellitus-related morbidity and mortality. Increased renin–angiotensin–aldosterone system activity and decreased β-adrenergic receptor (β-AR) responsiveness contribute to diabetic cardiac dysfunction. We evaluated the effect of sacubitril/valsartan (neprilysin inhibitor plus angiotensin receptor antagonist combination) and valsartan treatments on the diabetic cardiac function through β-AR responsiveness and on protein expression of diastolic components. Six-week-old male Sprague Dawley rats were divided into control, diabetic, sacubitril/valsartan (68 mg/kg)-, and valsartan-treated (31 mg/kg) diabetic groups. Diabetes was induced by a high-fat diet plus low-dose streptozotocin (30 mg/kg, intraperitoneal). After 10 weeks of diabetes, rats were treated for 4 weeks. Systolic/diastolic function was assessed by in vivo echocardiography and pressure–volume loop analysis. β-AR-mediated responsiveness was assessed by in vitro papillary muscle and Langendorff heart experiments. Protein expression of sarcoplasmic reticulum calcium ATPase2a, phospholamban, and phosphorylated phospholamban was determined by Western blot. Sacubitril/valsartan improved ejection fraction and fractional shortening to a similar extent as valsartan alone. None of the treatments affected in vivo diastolic parameters or the expression of related proteins. β₁-/β₂-AR-mediated responsiveness was partially restored in treated animals. β₃-AR-mediated cardiac relaxation (an indicator of diastolic function) responses were comparable among groups. The beneficial effect of sacubitril/valsartan on systolic function may be attributed to improved β₁-/β₂-AR responsiveness. Full article