Search Results (95)

Cardiovascular disorders and the medications used to treat them can affect physiological patterns of behavior. The aim of the present study was to determine whether the dual inhibition of neprilysin and angiotensin II—sacubitril/valsartan (ARNI) can modify anxiety-like behavior in male spontaneously hypertensive rats (SHR). We compared ARNI with two other drugs in the portfolio of heart failure treatment, captopril and ivabradine. Six groups (n = 13) of 12-week-old rats were treated for six weeks: control (Wistar rats), control + ARNI, SHR, SHR + ARNI, SHR + captopril, and SHR + ivabradine. The elevated plus maze test, the open field test, and the light–dark box test were used to determine anxiety-like behavior. SHRs exhibited higher systolic blood pressure (SBP), heart rate (HR), left ventricular weight (LVW), and hydroxyproline concentration (LVHP) but displayed a reduced level of anxiety-like behavior in comparison to controls. ARNI reduced SBP, HR, and LVW but had no significant effect on the level of anxiety in SHR, and similar results were achieved by captopril and ivabradine. Additionally, correlation analysis indicated that anxiety-like behavior in Wistar rats or SHR, either with or without cardiovascular therapy, was independent of SBP, HR, LVW, or LVHP. The level of anxiety-like behavior can, therefore, be considered part of the inherent neurobehavioral traits unrelated to fundamental hemodynamic or structural cardiovascular parameters. Full article

Background/Objectives: Cognitive impairment (CI) is a common complication of heart failure (HF) that undermines self-care, adherence, and outcomes. This systematic review assessed the cognitive effects of pharmacological HF management and related cardiovascular therapies, identifying potential risks and benefits. Methods: Following PRISMA 2020, we searched PubMed, EMBASE, and Scopus for articles published in English between 1 January 2010 and 31 January 2025 (last search 31 January 2025). We included RCTs and cohort studies in adults with HF or high cardiovascular risk that reported cognitive outcomes. Non-pharmacological interventions, studies without relevant cognitive endpoints, and non-original research were excluded. Risk of bias was assessed using RoB 2 for RCTs and the Newcastle–Ottawa Scale for observational studies. Due to heterogeneity in study designs and cognitive measures, results were synthesized qualitatively without meta-analysis. Results: Of 530 records screened, 11 studies encompassing 58,190 participants met the inclusion criteria. Intensive blood pressure (BP) lowering was consistently associated with reduced risk of mild cognitive impairment or dementia compared with standard BP control. In HF populations, sacubitril/valsartan showed no adverse cognitive effects versus other RAAS inhibitors. Across RCTs and observational studies, β-blockers, ACE inhibitors, ARBs, diuretics, and statins showed no evidence of significant cognitive impairment. Comparisons of anticoagulants (dabigatran vs. warfarin; warfarin vs. aspirin) revealed no differences in cognitive trajectories, while optimized medical therapy was associated with parallel improvements in cognitive scores, left ventricular function, and renal parameters. Limitations: Evidence remains constrained by heterogeneity in study design and cognitive assessment tools (often brief screening instruments), inconsistent reporting, and generally short follow-up durations, which may obscure subtle or long-term effects. Conclusions: Contemporary pharmacological therapies for HF appear cognitively safe. Intensive BP control may confer cognitive benefit in high-risk populations, while guideline-directed treatments show no consistent evidence of cognitive harm. Optimized medical therapy may even support cognitive improvement alongside cardiac and renal recovery. Routine cognitive assessment should be integrated into HF care to support individualized management. Full article

Heart failure with reduced ejection fraction (HFrEF) continues to impose a high burden of morbidity and mortality despite significant advances in pharmacologic and device-based therapy. Cardiac resynchronization therapy (CRT) and angiotensin receptor–neprilysin inhibitors (ARNIs) have independently demonstrated substantial benefits in symptoms, health-related quality of life (HRQoL), and survival. Cardiac rehabilitation (CR), incorporating structured exercise, education, and lifestyle optimization, is well established as an effective intervention in HFrEF, yet its role in the era of combined CRT and ARNI therapy remains insufficiently characterized. This literature review synthesizes current evidence on CR in HFrEF populations receiving CRT, ARNI, or both, highlighting its impact on HRQoL, exercise capacity, and functional outcomes. Across diverse study designs—including randomized trials, observational cohorts, and meta-analyses—CR consistently yielded clinically meaningful improvements in patient-reported HRQoL and objective measures such as six-minute walk distance (6MWD) and peak oxygen uptake. Data directly evaluating CR in patients concurrently receiving both CRT and ARNI are lacking; indirect evidence suggests CR is compatible with, and may add to, contemporary device and drug therapy. However, referral rates remain low, indicating an implementation gap despite strong evidence of benefit. The review underscores the importance of integrating CR into contemporary HFrEF care and identifies a pressing need for targeted prospective studies to define its role in patients receiving dual device–pharmacologic therapy. Full article

Background/Objectives: Heart failure with reduced ejection fraction (HFrEF) remains a major global health burden. Sacubitril/valsartan, an angiotensin receptor neprilysin inhibitor (ARNI), improves outcomes in HFrEF but may cause hyperkalemia. Methods: A single-center retrospective cohort study was conducted at King Abdulaziz Cardiac Center, Riyadh, including 238 HFrEF patients initiated on sacubitril/valsartan (2016–2021). Potassium levels were assessed pre-initiation and at 0–3, 3–6, and 6–12 months post-initiation. Hyperkalemia was analyzed at thresholds >5.0, >5.5, and >6.0 mmol/L. Results: Median age was 58 years (IQR 48–69); 75.2% were male. Hyperkalemia >5.0 mmol/L occurred in 44.4% (95% CI: 38.1–51.0) within three months post-initiation versus 8.2% (95% CI: 5.3–12.4) pre-initiation. Only 17.3% exceeded 5.5 mmol/L. Treatment discontinuation occurred in 7.1% of patients, with 1.3% stopping due to clinically significant hyperkalemia. McNemar’s test confirmed a significant increase in prevalence across time points (p < 0.0001). Conclusions: Despite increased hyperkalemia incidence, discontinuation rates were low, consistent with prior trials (PARADIGM-HF, PARAGON-HF). Sacubitril/valsartan remains an effective and generally safe therapy for HFrEF, with hyperkalemia manageable through monitoring. Limitations include missing potassium data, potential confounding factors, and the lack of a control group; future prospective studies with regular electrolyte monitoring are recommended. Full article

Background/Objectives: Angiotensin receptor–neprilysin inhibitor (ARNI) has a well-established advantage over angiotensin-converting enzyme inhibitor or angiotensin receptor blocker (ACEI/ARB) therapy in patients (pts) with heart failure with reduced ejection fraction (HFrEF), but in pts after acute myocardial infarction (AMI) with left ventricular (LV) systolic dysfunction, the advantage of ARNI has not been clearly proven. The efficacy of ARNI is compared with that of ACEI/ARB therapy in patients with their first AMI in terms of improvement of post-infarction LV systolic function. Methods: The study was conducted as a retrospective one-center cross-sectional analysis. Overall, 1473 pts (990 M, median age 71 [64; 77]) with AMI (their first AMI, complete coronary revascularization, no prior coronary revascularization or history of HF) hospitalized in 2022–2024 were enrolled in a retrospective cross-sectional analysis. The study population was categorized into pts receiving ARNI and ACEI/ARB. Then, based on the ARNI subgroup, matching that included age, sex, and LV ejection fraction (LVEF) was performed by using the 1:1 nearest neighbor method without returning. Finally, two groups (ARNI vs. ACEI/ARB) of 30 pts were obtained and analyzed at baseline and at a 6-week follow-up. The improvement of post-infarction LV systolic function was obtained in terms of LVEF, ΔLVEF, and relative ΔLVEF values (ΔLVEF/baseline LVEF). Results: The comparison of baseline characteristics revealed borderline lower initial LVEF (30 vs. 36%, p = 0.076) and a higher frequency of SGLT-2 inhibitor use (70% vs. 36.7%, p = 0.01) in the ARNI subgroup. At the 6-week follow-up, in both subgroups, a significant improvement in the median LVEF values was achieved—from a median LVEF value of 30% (27.3; 38) to 37% (30; 43; p = 0.0008) in the ARNI subgroup and from a median LVEF value of 36% (33; 39) to 45% (42; 52; p < 0.0001) in the ACEI/ARB subgroup. The median ΔLVEF in the ACEI/ARB subgroup was higher [10% (6; 12)] than in the ARNI subgroup [6% (2; 10.25), p = 0.018]. Similarly, the median relative ΔLVEF was higher in the ACEI/ARB subgroup [30% (15.4; 40)] than in the ARNI group [17.5% (7; 31.9), p = 0.047]. The vast majority of patients, particularly in the ARNI group (99.7%), were treated with the lowest available dose of the drug. Conclusions: Our current experience in ARNI therapy after AMI is promising; however, it is limited to a small group of patients with severe impairment of LV systolic function. Regardless of the significant improvement in the baseline LVEF observed in patients receiving both ACEI/ARB and ARNI at the 6-week follow-up, the absolute and relative increases in the LVEF were higher in subjects treated with ACEI/ARB. However, the clinical benefits of ARNI therapy may emerge more gradually, and its advantages could become more apparent over a longer follow-up period. The clinical efficacy of early use of ARNI in the setting of AMI needs further evaluation. Full article

Background: Sacubitril/Valsartan is a first-line treatment for heart failure with reduced ejection fraction (HFrEF) according to international guidelines. However, achieving the target doses of guideline-directed medical therapy (GDMT) remains a challenge in clinical practice and its efficacy at suboptimal dose (<200 mg/day) versus angiotensin-converting enzyme (ACE) inhibitors remains debated. Our objective was to evaluate the titration of Sacubitril/Valsartan within 3 months of hospital discharge in patients with HFrEF. Methods: A cross-sectional study was conducted in a secondary care hospital in Geneva, Switzerland. Patients hospitalized between 2020 and 2022 with HFrEF, discharged with Sacubitril/Valsartan, were included. Physicians managing patients discharged with a Sacubitril/Valsartan dose of less than 200 mg/day were contacted and asked to complete a structured 7-item questionnaire regarding dose adjustments within the first 3 months following hospital discharge. The primary outcome was the proportion of patients who did not achieve GDMT doses of Sacubitril/Valsartan, along with reasons for inadequate titration. Results: Overall, 30 patients out of 79 (38%, 95% confidence interval [27–49%]) had not been titrated to an effective dose of Sacubitril/Valsartan 3 months after hospitalization. Of these thirty patients, the primary reason for not titrating cited by their practitioners (n = 27) was that titration was perceived to be within the cardiologist’s scope of responsibility (15/27, 56%). While most physicians (66%) knew the target doses for Sacubitril/Valsartan, 83% of them were unaware that the clinical benefit of sacubitril/valsartan at doses below 50% of the target compared to ACE inhibitors remains uncertain and is not well supported by current evidence. Conclusions: In this cohort, more than a third of patients with HFrEF were not titrated to guideline-recommended target doses of sacubitril/valsartan within 3 months of hospital discharge. This finding raises questions about the clinical and economic value of initiating sacubitril/valsartan without subsequent dose optimization, especially given the uncertainty surrounding the efficacy of suboptimal dosing compared to ACE inhibitors. Full article

Background: Sacubitril/valsartan (S/V) improves left ventricular (LV) function and clinical outcome in heart failure (HF) with reduced ejection fraction (HFrEF). Data on its clinical value in the specific cohort of HFrEF patients demonstrating no adequate response to cardiac resynchronization therapy (CRT nonresponders; CRT-NRs) are limited. Herein, we investigated the impact of S/V initiated as a replacement for ACEi/ARB therapy in CRT nonresponder (CRT-NR) patients. Methods: Our HF database was searched to identify CRT-NRs who received S/V treatment for at least 6 months as a replacement for ACEi/ARB (Group I; 70 patients) and CRT-NRs who remained on ACEi/ARB (Group II, 70). In addition, HFrEF patients without CRT indication who received S/V therapy for at least 6 months (Group III; 135) were also included in this analysis. The primary endpoint was the composite of all-cause mortality including heart transplantation (HTx) or left ventricular assist device implantation (LVAD) and HF hospitalization (HFH). Secondary endpoints were (i) all-cause mortality+HTx+LVAD and (ii) HFH analyzed separately. Results: Over a median follow-up of 22 months, the primary composite endpoint occurred in 27 out of 70 patients (38.57%) in Group I, 43 out of 70 patients (61.42%) in Group II, and 60 out of 135 patients (44.42%) in Group III. The differences were significant between Groups I and II (p: 0.005), as well as between Group II and III (p: 0.012), while the two groups on S/V (Group I and III) demonstrated similar outcomes (p = 0.465). HFH analyzed separately as a secondary endpoint occurred in 19 out of 70 patients (27.14%) in Group I, 38 out of 70 patients (54.28%) in Group II, and 36 out of 135 patients (26.66%) in Group III (Group I vs. II p: 0.001; Groups II vs. III p: 0.001, Group I vs. III, p: 0.896). All-cause mortality+HTx+LVAD analyzed separately as the other secondary endpoint demonstrated no significant differences among the three groups. Conclusions: S/V therapy improved HFH but not mortality in CRT-NR patients. Comparable improvement was demonstrated after SV in the CRT-NR and in the general HFrEF cohort with no CRT indication. Full article

Background/Objective: Sacubitril/Valsartan are a combination drug approved for heart failure treatment, known to enhance natriuretic peptide activity and inhibit the renin–angiotensin–aldosterone system (RAAS). While its clinical efficacy is well-established, its broader impact on human metabolism remains insufficiently characterized. This study aimed to explore the time-resolved metabolic changes induced by Sacubitril/Valsartan in healthy individuals using an untargeted metabolomics approach. Methods: Fourteen healthy male volunteers received a single oral dose of Sacubitril/Valsartan (200 mg; 97.2 mg Sacubitril and 102.8 mg Valsartan) across two phases separated by a two-week washout period. Plasma samples were collected at eight individualized time points based on pharmacokinetic profiles. Metabolites were extracted and analyzed using high-resolution liquid chromatography–mass spectrometry (LC-QToF HRMS). Data processing included peak alignment, annotation via HMDB and METLIN, and statistical modeling through multivariate (PLS-DA, OPLS-DA) and univariate (ANOVA with FDR correction) analyses. Results: Out of 20,472 detected features, 13,840 were retained after quality filtering. A total of 315 metabolites were significantly dysregulated (FDR p < 0.05), of which 31 were confidently annotated as endogenous human metabolites. Among these, key changes were observed in the pyrimidine metabolism pathway, particularly elevated levels of uridine triphosphate (UTP) associated with cellular proliferation and metabolic remodeling. OPLS-DA models demonstrated clear separation between pre-dose and Cmax samples (R²Y = 0.993, Q² = 0.768), supporting the robustness of the time-dependent effects. Conclusions: This is the first study to characterize the dynamic metabolomic signature of Sacubitril/Valsartan in healthy humans. The findings reveal a distinctive perturbation in pyrimidine metabolism, suggesting possible links to drug mechanisms relevant to cardiac cell cycle regulation. These results underscore the utility of untargeted pharmacometabolomics in uncovering systemic drug effects and highlight potential biomarkers for monitoring therapeutic response or guiding precision treatment strategies in heart failure. Full article

Background and Objectives: Optimal pharmacological treatment following left ventricular ejection fraction (LVEF) improvement remains largely unknown. This study compared the clinical outcomes of patients with heart failure (HF) with improved EF (HFimpEF) based on the maintenance of sacubitril/valsartan (S/V) or transition to a renin–angiotensin system blocker (RASB). Material and Method: A total of 354 patients with recovered LVEF of at least 40% after S/V treatment from a single center were retrospectively analyzed. Patients were categorized into three groups: those who continued S/V (n = 294), those who switched to RASB (n = 47), and those who discontinued both S/V and RASB (n = 13). The primary endpoint was HF relapse, defined as a two-fold increase in baseline serum N-terminal-pro hormone B-type natriuretic peptide (NT-proBNP) concentration exceeding 400 pg/dL. Secondary endpoints included the ratio and difference between baseline and peak NT-proBNP levels. Result: Baseline clinical characteristics were well balanced among groups. Over a median follow-up of 399 (252–589) days, HF relapse occurred more frequently in patients who discontinued both S/V and RASB compared to those who maintained either treatment (53.8% vs. 16.3% vs. 10.6%; p = 0.001). NT-proBNP levels also showed a more pronounced increase in this group. However, there were no significant differences in primary or secondary outcomes between the S/V and RASB groups. Conclusions: Our findings suggest that replacing S/V with another RASB does not worsen outcomes in patients with HFimpEF after S/V treatment, whereas discontinuation of both therapies is associated with a significantly higher risk of HF relapse. A prospective trial is warranted to confirm the safety and effectiveness of this approach in maintaining remission. Full article

Background: Adherence to current clinical guidelines is crucial for ensuring optimal therapy in patients with heart failure (HF). This study aims to explore how cardiologists, as specialists in heart failure, approach the clinical scenarios encountered in the management of HF patients, in line with the recommended guidelines. A heart failure-focused meeting was organized, during which participating cardiologists engaged actively. During HF meetings in which cardiologists participated, 108 questionnaires were distributed electronically. In total, 57 men and 51 women expressed their opinions regarding the Delphi analysis. Results: A strong consensus on the benefits of beta-blockers in improving prognoses for, and reducing mortality in, patients with HF and reduced systolic function emerged. The majority of cardiologists continue to prefer intravenous therapy with continuous loop-diuretic administration in combination with thiazide diuretics. The use of metolazone elicits fewer preferences, probably due to concerns about side effects. Certainly, SGLT2i is useful in reducing hospitalizations and reducing congestion; however, there is no full consensus on whether MRAi should be discontinued in favor of SGLT2i alone. The majority of participants would discontinue MRAs in the presence of hyperkalemia and worsening renal function, maintaining sacubitril/valsartan, and indicating a priority for renal safety. There was near-unanimous agreement on the early initiation of sacubitril/valsartan after the stabilization of patients hospitalized for heart failure. Conclusions: A significant majority (97%) of cardiologists expressed a preference for utilizing all of the guideline-recommended drug classes in the management of heart failure, even if this meant not always reaching the maximum tolerated dose for each medication. This approach underscores the importance of comprehensive therapy, targeting multiple pathophysiological mechanisms in heart failure. Cardiologists emphasized that while achieving optimal dosing is ideal, flexibility in treatment regimens is often necessary to accommodate individual patient characteristics, tolerance, and clinical status. The findings highlight the need for personalized treatment strategies that align with current guidelines, while also recognizing the challenges and variability in patient responses to therapy. Full article

Background: Despite improvements in medical therapy, heart failure with reduced ejection fraction (HFrEF) is a major burden on the healthcare system and remains a leading cause of death with a 5-year mortality rate of more than 60%. Novel therapeutic agents such as angiotensin-receptor-neprilysin-inhibitors (ARNIs) lead to significant improvement in clinical outcomes. Optimal therapy monitoring under these novel drugs is crucial for improving the outcome. In this trial, the diagnostic potential of four novel cardiovascular biomarkers—GDF-15, sST2, H-FABP, and suPAR—was evaluated during follow-up in patients with HFrEF. Methods: In this prospective cohort pilot study, 70 patients with HFrEF with ischemic (n = 34) and non-ischemic (n = 36) origin were included. All included patients were on a stable treatment regimen and in a non-decompensated state. The clinical parameters NYHA class, LVEF, MPI/Tei index and ESC Score 2 and the laboratory parameters sST2 (remodeling, inflammation), GDF-15 (remodeling, inflammation), H-FABP (subclinical ischemia and ischemia), suPAR (remodeling, inflammation) and NT-proBNP were assessed before ARNI therapy initiation and at 3 to 6 months at follow-up. Before starting ARNI therapy with sacubitril/valsartan patients had stable and well-established heart failure therapy. Results: There was a sufficient response to therapy with significant improvement in ejection fraction from 29.9% to 38.5% (p < 0.001) and a significant decrease in NT-proBNP from 1402 pg/mL to 572.0 pg/mL (p = 0.003). Interestingly, along with that, a significant increase in sST2 levels from 9602 pg/mL to 12,001 pg/mL (p = 0.039) but no significant change in H-FABP (p = 0.397), GDF-15 (p = 0.382) or suPAR (p = 0.328) were observed. Furthermore, the baseline sST2 level correlated with the risk of cardiovascular events calculated with the ESC Score 2 and the GDF15 level at follow-up correlated with the right ventricular global function, assessed with the MPI/Tei index and this correlation persisted after correction for confounders (r = 0.323, p = 0.039; r = 0.504, p = 0.011). Conclusions: The novel biomarker sST2 but not H-FABP, GDF-15 and suPAR was significantly affected by medical therapy with ARNIs. Monitoring sST2 might offer new opportunities for therapy guidance and disease management. However, these results are hypothesis generating and should be interpreted with caution, given the pilot nature of this study. 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

Heart failure (HF) is a highly prevalent cardiovascular clinical syndrome. Health care spending on HF treatment is high. Therefore, its treatment has generated a great deal of interest in pharmacological research in recent years. Recent guidelines have introduced several molecules for the treatment of HF that have demonstrated safety, and above all, efficacy. One of the worst aspects of HF is ventricular dyssynchrony (VD) with a wide QRS interval. Currently, the cornerstone of VD therapy is cardiac resynchronization therapy (CRT). Our comprehensive review aims to analyze the effects of new molecules on QRS width and understand whether these molecules can provide benefits. Full article

Sodium–glucose cotransporter 2 inhibitors (iSGLT2) have become the fourth pillar of the medical treatment for heart failure with reduced ejection fraction (HFrEF). However, the mechanisms of action of iSGLT2 remain poorly understood. The effectiveness of combined ARNI and iSGLT2 therapy in left ventricular (LV) remodeling is still under study. We aim to investigate the effects of ARNI + iSGLT2 combination therapy in patients affected by HFrEF in terms of ventricular remodeling using speckle tracking echocardiography (STE). In this observational study, 136 patients with HFrEF taking ARNI were enrolled. All patients were evaluated at baseline (before iSGLT2), at 3 months and at 12 months from the beginning of iSGLT2 therapy. Echocardiographic parameters, including STE analysis and volumetric and LV contractile function indices, were collected at the three timepoints. The objectives were (1) to evaluate the effects of ARNI + iSGLT2 combination therapy on ultrasound (US) measurements; (2) to evaluate the effects on the variation of laboratory data indicative of HF (NT-pro-BNP); and (3) to evaluate the medium-long term impact of the ARNI + iSGLT2 combination therapy in terms of major cardiovascular events (MACVE). After only three months of combined ARNI + iSGLT2 therapy, we reported a significant improvement in ventricular and atrial volumetric indices, systolic function indices and myocardial deformation parameters assessed by STE. We also reported a significant decrease in NTproBNP levels. This trend was confirmed at 12 months follow-up. Furthermore, narrowing down the analysis to patients who were already treated with ARNI when they started taking iSGLT2, we reported similar results in the improvement of US parameters and NTproBNP levels. Our study has shown that the ARNI + iSGLT2 combination therapy leads to a clinical improvement and positive ventricular remodeling. Even the single introduction of additional iSGLT-2 in HFrEF patients on an otherwise optimized therapy resulted in a significant improvement in US and laboratory variables. The results of our study suggest implementing iSGLT-2 therapy as soon as possible, as the structural and functional cardiac improvements achieved by these drugs are achieved in the short term and maintained in the long term. 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