Search Results (4,711)

Background: Implant-surface decontamination is required before reconstructive treatment of peri-implantitis, but no protocol has demonstrated consistent clinical superiority. Objective: To compare the immediate reduction in recoverable bacterial target DNA after electrolytic cleaning and 0.2% chlorhexidine (CHX). Materials and Methods: Forty nonsmoking patients with peri-implantitis (one implant per patient) were randomized to GalvoSurge (n = 20) or CHX (n = 20). Microbiological samples were collected from the exposed implant surface before and immediately after the assigned decontamination protocol and standardized terminal sterile-saline irrigation. Five periodontal pathogens were assessed using semiquantitative DNA-based real-time PCR (qPCR). Laboratory categories were converted to an exploratory summed ordinal score (range 0–15). A post hoc cumulative logit model compared post-treatment scores between groups while adjusting for the pretreatment score. Results: Pretreatment scores were higher in the GalvoSurge group (median 4.5, IQR 3.0–6.0) than in the CHX group (median 3.0, IQR 2.75–4.0; p = 0.043). After baseline adjustment, GalvoSurge was associated with lower post-treatment scores (adjusted common odds ratio for a higher score, 0.047; 95% profile-likelihood CI, 0.009–0.202; p < 0.001). Unadjusted analyses also favored GalvoSurge for absolute reduction (median 4.0 vs. 1.0), relative reduction (83.3% vs. 26.7%), and post-treatment score (median 1.0 vs. 2.0; all p < 0.001). Complete target non-detection occurred in 7/20 (35.0%) and 2/20 (10.0%) patients, respectively (Fisher’s exact p = 0.127). Conclusions: In this exploratory randomized pilot sample, GalvoSurge was associated with a greater immediate reduction in recoverable bacterial target DNA than CHX after adjustment for pretreatment score. DNA-based qPCR does not distinguish viable from non-viable bacteria; therefore, the findings do not establish bacterial killing, sterility, or long-term clinical superiority. Full article

Background/Objectives: The development of multifunctional biomaterials for bone regeneration remains a key challenge in additive manufacturing. Although polylactic acid (PLA) is widely used in fused deposition modeling (FDM), its limited bioactivity and lack of intrinsic antibacterial functionality restrict its application in implantable constructs. This study aimed to develop a PLA-based composite filament combining ion-mediated bioactive potential and local antibacterial functionality using a Quality by Design (QbD) approach. Methods: PLA-based composite filaments incorporating a mollusk shell-derived biogenic calcium-containing filler (20 wt.%) and gentamicin (5 wt.%) were fabricated by solvent-free melt extrusion. A QbD framework was applied to define the Quality Target Product Profile (QTPP), identify critical quality attributes (CQAs), and assess critical material attributes (CMAs) and critical process parameters (CPPs). The material was characterized by SEM–EDS combined with ImageJ-based quantitative image analysis, TGA/DSC, mechanical testing, ICP-AES analysis of aqueous extracts, agar diffusion antibacterial assays, FDM printability assessment, and in vivo biocompatibility testing in a rat subcutaneous implantation model. Results: The developed PLA–Gen–MS material was obtained as a continuous filament with a diameter of 1.75 ± 0.05 mm and was successfully used for FDM printing of model scaffold structures. SEM–EDS confirmed matrix continuity and distribution of the calcium-containing mineral phase. ICP-AES revealed a calcium-dominant multicomponent ion release profile, with Ca as the predominant element and measurable levels of Sr, Mg, P, Mn, and Fe. TGA/DSC confirmed thermal compatibility of the components under melt-processing conditions. PLA–Gen–MS demonstrated antibacterial activity against all tested strains, with inhibition zones of approximately 20–21 mm. In vivo, the material showed a favorable preliminary tissue response compared with TiLOOP^®, including faster reduction of inflammatory infiltration and absence of foreign body giant cells by day 14. Conclusions: The QbD-guided strategy enabled the development of a multifunctional PLA-based filament integrating melt processability, structural integrity, ion-mediated bioactive potential, antibacterial functionality, printability, and favorable preliminary biocompatibility. PLA–Gen–MS can be considered a promising platform for further development of personalized bioactive and antibacterial scaffold constructs for bone regeneration. Full article

Periprosthetic joint infection (PJI) remains one of the most serious complications of arthroplasty, largely due to the formation of microbial biofilms on implant surfaces. Biofilm-associated infections exhibit increased tolerance to antimicrobial therapy and host immune responses, making eradication difficult and often requiring repeated surgical interventions. Consequently, there is a growing need for effective local therapeutic strategies capable of delivering high concentrations of antimicrobial agents directly to the site of infection while minimizing systemic toxicity. Hydrogels have emerged as promising drug delivery platforms for the management of biofilm-associated PJI. Their biocompatibility, injectability, high water content, and tunable physicochemical properties enable controlled and localized release of therapeutic agents within the infected peri-implant environment. This narrative review summarizes recent advances in hydrogel-based approaches, including antibiotic-loaded hydrogels, systems incorporating anti-biofilm enzymes, bacteriophage-loaded formulations, and nanoparticle-enhanced platforms. It also highlights future research directions, with particular emphasis on the need for expanded clinical studies to facilitate the translation of emerging hydrogel-based therapies into clinical practice. Further development of these systems should focus on the incorporation of novel therapeutic agents into hydrogel platforms, aiming to enhance biofilm eradication and improve treatment outcomes in patients with PJI. Particular attention is given to stimuli-responsive (“smart”) hydrogels that release therapeutic payloads in response to infection-related triggers such as pH changes, with emphasis on the need for expanded clinical studies to facilitate the translation of emerging hydrogel-based therapies into clinical practice. Further development of these systems should focus on the incorporation of novel therapeutic agents into hydrogel platforms, aiming to enhance biofilm eradication and improve treatment outcomes in patients with PJI. Full article

Titanium alloys are widely used in clinical settings due to their excellent mechanical properties and biocompatibility. However, the biologically inert surface of titanium alloys limits interfacial bioactivity and bone integration, which may compromise long-term implant stability. Therefore, this study innovatively proposes a synergistic “composition design and process adaptation” strategy. Specifically, borosilicate bioactive glasses (BSBGs) with a high B₂O₃ content (36 mol%), co-doped with strontium (Sr) and magnesium (Mg), were designed and systematically compared with Sr/Mg-doped silicate bioactive glasses (SBGs). Both glasses were subsequently deposited onto Ti6Al4V substrates using atmospheric plasma spraying. The results showed that the BSBG coating exhibited an initial boron release concentration of up to 116 mg/L but exhibited excellent cytocompatibility, which is likely related to the synergistic regulation of Sr, Mg, and B ions. Moreover, the BSBG coating induced Ca-P compound mineralization within 24 h, significantly faster than the SBG coating, which required a minimum of 3 days, confirming superior biomineralization kinetics. Both coatings achieved a bonding strength of 30 MPa, meeting clinical requirements. In vivo experiments confirmed that the BSBG coating significantly promoted new bone regeneration and implant osseointegration. This work not only delivers experimental validation supporting the implementation of high-boron-content bioactive glass coatings but also provides a practical method for designing rapidly degradable and highly bioactive coatings to facilitate improved osseointegration. Full article

Background and Objectives: Cerebrovascular events remain among the most feared complications after transcatheter aortic valve implantation (TAVI). Whether early and post-discharge cerebrovascular events are associated with distinct clinical, echocardiographic, haemodynamic, and procedural predictors remains incompletely clarified. Materials and Methods: This retrospective, observational, two-center cohort study included 556 patients who underwent TAVI for severe symptomatic aortic stenosis between October 2011 and May 2023. The primary outcomes were in-hospital stroke and mid-to-long term stroke occurring after hospital discharge. Stroke diagnoses were established by neurological assessment and confirmed by cranial computed tomography and/or magnetic resonance imaging. Univariable comparisons and Firth penalized multivariable logistic regression analyses were performed to identify predictors of each outcome. Results: In-hospital stroke occurred in 14 patients (2.5%), whereas mid-to-long term stroke occurred in 16 patients (2.9%). In Firth penalized multivariable analysis, baseline mitral regurgitation grade (odds ratio [OR] 2.174, 95% confidence interval [CI] 1.299–3.638; p = 0.003), HbA1c (OR 1.644, 95% CI 1.111–2.433; p = 0.013), and prior cerebrovascular event (OR 4.269, 95% CI 1.150–15.846; p = 0.030) were independently associated with in-hospital stroke. For mid-to-long term stroke, post-dilatation (OR 9.862, 95% CI 2.555–38.067; p < 0.001) and very severe aortic stenosis phenotype (OR 3.649, 95% CI 1.343–9.916; p = 0.011) were independently associated with the outcome. Conclusions: Early and post-discharge cerebrovascular events after TAVI were infrequent but associated with distinct predictor profiles. In-hospital stroke was associated with baseline mitral regurgitation grade, HbA1c, and prior cerebrovascular event, whereas mid-to-long term stroke was associated with post-dilatation and very severe aortic stenosis phenotype. Given the limited number of events, these findings should be interpreted as exploratory and require validation in larger prospective cohorts. Full article

A naive Bayesian classifier (NBC) combined with principal component analysis (PCA) effectively differentiates the dose-dependent effects of certain groups of psychoactive drugs based on their impact on the amplitude–spectral characteristics of electrocorticograms (ECoG) in rats. This approach has been shown to be useful for pharmacological screening of agents with unknown or poorly understood activity. Despite previously obtained optimistic results, classification determination for some drugs was inaccurate, necessitating the search for possible ways to improve the predictive effectiveness of the proposed algorithm. One possible approach would be to use as input quantitative data not only the impact of the psychoactive drugs studied on the amplitude–spectral characteristics of ECoG but also connectivity changes, including the average coherence power of different pairs of leads. The aim of this study was to compare the accuracy of NBC in classifying the pharmacological mechanism of action of agents with well-known mechanisms (test set) using pharmaco-EEG data on changes in the amplitude–spectral characteristics of ECoG, coherence, and the combined use of two data sets. Materials and methods. Experiments were performed on Wistar rats with chronically implanted ECoG electrodes. The training set, relative to which the effects of the pharmacological agents from the test set were classified, were the matrices of effects of 12 pharmacological agents: the NMDA antagonist dizocilpine, the D2/D3 antagonists haloperidol and sulpiride, the M-anticholinergic tropicamide, the H1/5HT2A receptor blocker hydroxyzine, the acetylcholinesterase inhibitor galantamine, the alpha-2 adrenergic agonist dexmedetomidine, the alpha-2 adrenergic antagonist atipamezole, the adenosine receptor blocker caffeine and the GABA-mimetics aminophenylbutyric acid (phenibut), bromdihydrochlorophenylbenzodiazepine (phenazepam) and 5-ethyl-5-phenyl-2,4,6(1H,3H,5H)-pyrimidinetrione. The test set included various drugs with tropism for the targets of the training set drugs: dopamine receptor antagonists chlorpromazine, droperidol, tiapride and raclopride, H1-histamine blockers diphenhydramine and promethazine, 5-HT2-receptor blockers ritanserin and glemenserin, acetylcholinesterase inhibitor ipidacrine, alpha2-adrenergic receptor antagonist yohimbine, alpha2-adrenergic agonists medetomidine and xylazine, GABA-mimetics 5-ethyl-5-(1-methylbutyl)-2,4,6(1H,3H,5H)-pyrimidinetrione and chloral hydrate. The analysis of the ECoG signal included the calculation of 132 amplitude–spectral characteristics and 75 coherence indicators, which, using the PCA, led to new integrative indicators used for further classification of the NBC. Results and discussion. For each drug in the test set, the median similarity probability with a particular group from the training set was calculated, which was used to assess the classification quality. It was found that, when using the amplitude–spectral characteristics of ECoG, the proposed methodological approach allows for the identification of the ECoG effects of several groups of psychoactive drugs, including D2/D3-dopamine, M-cholinergic, H1-histamine, and 5-HT2-serotonin receptor blockers, AChE inhibitors, GABA-mimetics, and alpha-2-adrenergic receptor agonists and antagonists. This approach enabled the correct classification of 18 of 24 groups in the test set. When using changes in coherence indices as the initial data, the classification accuracy also amounted to 18 of 24 groups. When combining the two data sets, the number of correctly identified NBC groups was 20 of 24 groups. When comparing the classification during training (confusion matrix), it was found that coherence data or adding coherence data to the data based on changes in amplitude–spectral characteristics leads to a statistically significant (p < 0.01 in both cases) increase in accuracy. Conclusions. The obtained data demonstrated high accuracy in classifying the pharmacological activity of the test sample drugs using any of the three compared approaches. Despite the lack of statistically significant differences between them, classification based on the combined dataset demonstrated a higher number of “correct” similarities. This allows us to recommend the approach based on combined data of drug effects on amplitude–spectral characteristics and coherence as the most promising for further studies using pharmaco-EEG screening. Full article

Background and Objectives: Conduction disorders (CDs) and permanent pacemaker implantation (PPI) remain among the most common complications after transcatheter aortic valve implantation (TAVI). Given their potential impact on long-term outcomes, improved preprocedural identification of patients at high risk for new-onset CDs is increasingly important. We investigated whether selected preprocedural inflammatory and fibrotic biomarkers, along with echocardiographic indices of regional myocardial remodeling, were associated with new-onset CDs after TAVI. Materials and Methods: This single-center prospective observational study included 112 patients with severe aortic stenosis undergoing TAVI. Peripheral blood samples were obtained within 24 h before TAVI for measurement of inflammatory and fibrotic biomarkers, including interleukin-6 (IL-6), C-reactive protein (CRP), CRP-to-albumin ratio (CAR), procalcitonin, ferritin, lactate dehydrogenase, and transforming growth factor-β1. The primary outcome was the occurrence of new-onset CDs during the index hospitalization or within three months after TAVI. Results: New-onset CDs occurred in 58 patients (51.8%). IL-6 showed the strongest association with the outcome in univariable analysis (OR per 1-SD increase, 9.55; 95% CI 3.00–30.40; p < 0.001), remained associated after adjustment for selected clinical and procedural predictors in exploratory models (adjusted OR 10.70; 95% CI 2.43–47.07; p = 0.002), and demonstrated the highest, although moderate, discriminatory performance among the evaluated biomarkers (AUC 0.730; 95% CI 0.637–0.823). CRP and CAR were higher in patients with CDs and were significant in univariable analysis, but showed weaker and less consistent adjusted associations. Among echocardiographic markers, AB strain ratio ≥ 2 was the most consistent imaging correlate in exploratory biomarker–echocardiographic models. Conclusions: Elevated preprocedural IL-6 was the biomarker most consistently associated with new-onset CDs after TAVI. These findings suggest that higher preprocedural IL-6 levels may reflect patient-specific susceptibility to new-onset CDs after TAVI and could have potential value as an adjunctive biomarker, alongside echocardiographic assessment, for preprocedural risk evaluation, with further validation required in larger prospective studies. Full article

The long-term prognosis of left ventricular noncompaction (LVNC) compared to dilated cardiomyopathy (DCM) remains inconclusive, as prior studies have frequently failed to adequately adjust for heart failure severity. We conducted a single-center, retrospective, comparative study enrolling 96 patients with dilated LVNC (dLVNC) and 437 patients with DCM diagnosed at Peking Union Medical College Hospital between January 2010 and December 2022. dLVNC was defined as meeting the Jenni criteria, with left ventricular ejection fraction (LVEF) ≤45% and increased left ventricular end-diastolic diameter (LVEDD). A 1:1 propensity score matching (PSM) was performed, with matching variables including sex, age, history of heart failure (HF) hospitalization, arrhythmia, LVEF, and LVEDD, resulting in 96 matched pairs. The primary endpoint was major adverse cardiovascular events (MACEs), comprising cardiovascular death or heart transplantation, HF hospitalization or cardiac resynchronization therapy implantation, severe arrhythmias, and systemic embolism. After a median follow-up of 5.46 (2.14–8.62) years in the dLVNC group and 5.26 (2.47–8.50) years in the DCM group, the Kaplan–Meier survival curves between the groups were highly overlapping and revealed no significant differences in MACEs (log-rank p = 0.88), all-cause mortality (log-rank p = 0.84), and individual components of MACEs. After adjusting for heart failure severity, dLVNC and DCM exhibit no substantial difference in long-term prognosis, and the morphological feature of excessive trabeculation itself does not independently increase the risk of adverse events. Full article

Endometrial senescence and the endometrial microbiota have both been implicated in the regulation of endometrial receptivity, yet their relationship remains poorly understood. The aim of this study was to investigate associations between p16-positive endometrial cells and microbiota composition during the implantation window and to determine whether these relationships differ according to implantation outcome. Endometrial senescence was assessed by p16 immunohistochemistry and digital image analysis, whereas microbial composition was characterized by 16S rRNA gene sequencing in endometrial biopsies collected from 68 women prior to undergoing transfer of a single euploid embryo, which was performed within six months of biopsy under the same hormonal preparation protocol. No significant differences in luminal epithelial or stromal p16 abundance were observed according to subsequent implantation outcome. Although senescence was not directly associated with implantation success, stromal p16 expression demonstrated multiple associations with the endometrial microbiota. Increased stromal p16-positivity was associated with lower relative abundance of Lactobacillus and higher abundance of Delftia. Notably, in exploratory subgroup analyses more pronounced associations were observed in women who achieved pregnancy, including a negative correlation between stromal p16 expression and Lactobacillus abundance (ρ = −0.48, p = 0.005) and positive correlation with Delftia abundance (ρ = 0.42, p = 0.016). Species-level analyses revealed implantation outcome-specific associations involving Lactobacillus iners and Limosilactobacillus vaginalis. In addition, stromal p16 expression was associated with differences in microbial co-occurrence networks, indicating broader effects on microbial community organization. Together, these findings suggest that stromal, but not luminal, senescence is closely linked to endometrial microbiota composition and microbial community organization during the window of implantation. The observation that the strongest senescence–microbiota associations occurred in women who subsequently achieved successful implantation supports the hypothesis that coordinated senescence–microbiota relationships may represent a previously underrecognized feature of the receptive endometrial microenvironment. Full article

Benefiting from excellent high-frequency characteristics and superior radiation tolerance, InP is an indispensable material for next-generation high-speed communications, widely applied in optical communication, 6G radio frequency chips, AI optical interconnection, and aerospace radiation-hardened electronics. Although ion implantation greatly promotes the performance optimization of InP-based devices, it inevitably induces lattice displacement defects that degrade device reliability. Hence, quantitative evaluation of the threshold displacement energy (TDE) and dominant defect configurations in InP is essential. Our calculations reveal that the average threshold displacement energy is 18.20 eV for In atoms and 18.94 eV for P atoms. The E_d distributions for both In and P atoms predominantly lie below 30 eV and rarely exceed 40 eV. From 150 K to 900 K, In and P have a large mass difference and exhibit distinct temperature-dependent trends. The threshold displacement energy of In decreases with increasing temperature, whereas that of P rises as temperature increases. Based on the structural analysis of Frenkel pairs formed by displaced atoms, the dominant interstitial configurations are identified. These results provide detailed insights for damage evaluation and defect structure characterization in InP, benefiting ion implantation process optimization and radiation-hardening design of InP electronic devices. Full article

Primary implant stability arises from mechanical engagement at placement, and insertion torque is not a direct measure of osseointegration. This retrospective single-centre study included 101 MultiNeO titanium implant placements in 55 adults treated between April 2023 and January 2026. Four experienced operators placed implants subcrestally using a W&H Implantmed SI-1023, a bone-resistance-adapted drilling protocol, and a programmed target of 35 N·cm. Associations with recorded torque were assessed using a patient-clustered Gaussian generalized estimating equation adjusted for sex, age, anatomical sector, implant length and diameter, hard-tissue augmentation, and placement timing. The mean torque was 31.63 ± 5.57 N·cm; the median was 35 N·cm (Q1–Q3, 30–35). Recorded torque was 3.25 N·cm higher for implants placed in women than for those placed in men (95% CI 1.20–5.31; p = 0.002). Relative to maxillary anterior/premolar sites, mandibular molar sites showed higher torque (β = 4.02; p = 0.001), whereas mandibular anterior/premolar sites showed lower torque (β = −5.41; p = 0.013). Implant length had a modest adjusted association (β = 0.93 N·cm/mm; p = 0.022); age, diameter, augmentation, and placement timing did not. The concentration of recorded values at 35 N·cm reflects a clinical target rather than the device limit. These exploratory associations do not establish an intrinsic sex effect or predict osseointegration, and residual confounding due to unmeasured bone characteristics remains possible. Full article

Responsive neurostimulation (RNS) is a neuromodulation option for treatment of drug-resistant epilepsy (DRE). There is limited data reviewing bilateral thalamic and corticothalamic RNS therapy response. We performed a retrospective analysis of 21 patients undergoing RNS implantation with either bilateral thalamic (n = 17) or corticothalamic (n = 4) leads and ≥6 months of follow-up. Patients were classified as responders (≥50% seizure frequency reduction) vs. non-responders (<50% seizure frequency reduction). Among the bilateral thalamic cohort, 12/17 (70.6%) patients were responders, and 15/17 (88.2%) patients reported reduction in seizure severity. Pre-RNS seizure frequency was higher in bilateral thalamic nonresponders, although not found to be significant (median 13 vs. 30 seizures per month, p = 0.20). Among the corticothalamic cohort, 3/4 (75.0%) patients were responders, and all patients demonstrated improvement in seizure severity. These findings suggest that although bilateral thalamic targets were selected at our center more often, both bilateral thalamic and corticothalamic RNS approaches provided seizure frequency reduction. The majority of patients, including non-responders, reported seizure severity alleviation. Full article

Objectives: The aim of this study was to compare the surgical and postoperative clinical outcomes of punch-only and linear incision techniques for implantation of the Ponto^® bone conduction implant. Methods: Surgical and follow-up data were collected from 101 patients: 46 treated with Minimally Invasive Ponto^® Surgery (MIPS) and 55 with the linear incision technique (LT). The analysis focused on: (1) the surgical procedure, including operative time and intraoperative complications; (2) the healing process; and (3) long-term implant-site outcomes, including implant loss. Results: Median operative time was significantly shorter for MIPS than for LT (30 min vs. 40 min, p < 0.001). No major intraoperative complications were observed in either group. Adverse skin reactions were more frequent in the LT group than in the MIPS group (18.2% vs. 8.7%), but the difference was not statistically significant (p = 0.249). A single implant loss occurred in the LT group 18 months after surgery and was unrelated to failed osseointegration or the surgical technique, being caused by recurrent cholesteatoma. Conclusions: MIPS was associated with a significantly shorter operative time than the LT. Both MIPS and LT appear to be safe techniques. No statistically significant differences were detected between the groups with respect to adverse skin reactions or implant survival during the follow-up period. Full article

In this work, scanning microwave microscopy (SMM) is used to monitor the evolution of the local microwave response, in terms of variations in the S₁₁ input reflection coefficient, in two III–V heterostructures relevant to mid-infrared photonics, namely a 150 nm thick heavily doped InGaAs layer on InP and HfO₂ (35 nm)/InGaAs (150 nm)/InP, subjected to Ga⁺ FIB milling over a broad dose range. By correlating raw, uncalibrated two-dimensional S₁₁ maps with atomic force microscopy (AFM) and Raman spectroscopy, we observe a dose-dependent evolution from implantation-dominated behavior to progressive amorphization, layer thinning and surface roughening. In the uncapped InGaAs/InP system, the SMM response varies monotonically with ion dose, consistent with progressive FIB-induced modification of the exposed InGaAs layer and, at larger milling depths, of the underlying InP substrate. In the HfO₂-capped structure, the microwave response is more complex: the oxide initially acts as a partial buffer against ion penetration, delaying damage transfer, but this effect progressively weakens as the cap is thinned and structurally degraded. The resulting S₁₁ contrast may reflect the combined effects of FIB-induced structural modifications, layer removal, local material composition, and surface morphology. Overall, the combined dataset indicates that SMM is a potentially highly sensitive probe of FIB-induced nanoscale modifications in the local microwave response, especially at low doses, provided that suitable on-chip calibration and de-embedding structures are available. Full article

Background: Sacubitril/valsartan is a cornerstone of guideline-directed medical therapy for heart failure with reduced ejection fraction (HFrEF), yet data regarding reverse remodeling after ARNI initiation in patients previously treated with cardiac resynchronization therapy (CRT) remain limited. This study evaluated echocardiographic reverse remodeling following sacubitril/valsartan initiation in a real-world cohort of CRT-treated patients and explored the association between treatment timing and remodeling response. Methods: This single-center retrospective pilot study included 188 patients with HFrEF treated with CRT who subsequently initiated sacubitril/valsartan. Patients were categorized into early (≤12 months after CRT, n = 112) and late (>12 months, n = 76) initiation groups. Echocardiographic parameters and functional status were assessed at baseline and at approximately 12 months. Reverse remodeling was evaluated using changes in left ventricular ejection fraction (LVEF), ventricular volumes, and clinical status. Multivariable logistic regression was used to explore factors associated with reverse remodeling (ΔLVEF ≥ 10%). Results: Sacubitril/valsartan therapy was associated with significant improvements in LVEF, left ventricular end-diastolic volume, left atrial volume, and NYHA functional class in both groups. The magnitude of improvement in echocardiographic parameters was similar between early and late initiation groups. In exploratory multivariable analyses, earlier ARNI initiation was associated with clinically meaningful reverse remodeling (ΔLVEF ≥ 10%) (OR 6.36, 95% CI 1.59–25.50, p = 0.009). SGLT2 inhibitor therapy was also associated with reverse remodeling (OR 5.76, 95% CI 1.86–17.87, p = 0.002), while a longer CRT-to-ARNI interval was associated with lower odds of response (OR 0.77 per year, 95% CI 0.62–0.96, p = 0.018). Analysis of CRT-to-ARNI interval as a continuous variable showed only a weak association with reverse remodeling, while receiver operating characteristic analysis did not identify a meaningful temporal threshold (AUC 0.497). Conclusions: Sacubitril/valsartan initiation after CRT was associated with significant reverse remodeling, including in patients who initiated therapy several years after CRT implantation, although the late-initiation subgroup was of limited size, and treatment intervals beyond the interquartile range (4.0–7.0 years) were sparsely represented. Absolute echocardiographic improvements were broadly similar between groups, and receiver operating characteristic analysis did not identify a discriminative temporal threshold (AUC 0.497), indicating no discriminative ability beyond chance. Exploratory multivariable analysis identified an association between earlier initiation and clinically meaningful reverse remodeling, but this finding was not supported by a clinically meaningful temporal threshold. Full article