Search Results (311)

Background: Bipolar disorder (BD) is a chronic and disabling psychiatric condition characterized by recurring episodes of mania, hypomania, and depression. Despite the availability of mood stabilizers, antipsychotics, and antidepressants, long-term management remains challenging due to incomplete symptom control, adverse effects, and high relapse rates. Methods: This paper is a narrative review aimed at synthesizing emerging trends and future directions in the pharmacological treatment of BD. Results: Future pharmacotherapy for BD is likely to shift toward precision medicine, leveraging advances in genetics, biomarkers, and neuroimaging to guide personalized treatment strategies. Novel drug development will also target previously underexplored mechanisms, such as inflammation, mitochondrial dysfunction, circadian rhythm disturbances, and glutamatergic dysregulation. Physiological endophenotypes, such as immune-metabolic profiles, circadian rhythms, and stress reactivity, are emerging as promising translational tools for tailoring treatment and reducing associated somatic comorbidity and mortality. Recognition of the heterogeneous longitudinal trajectories of BD, including chronic mixed states, long depressive episodes, or intermittent manic phases, has underscored the value of clinical staging models to inform both pharmacological strategies and biomarker research. Disrupted circadian rhythms and associated chronotypes further support the development of individualized chronotherapeutic interventions. Emerging chronotherapeutic approaches based on individual biological rhythms, along with innovative monitoring strategies such as saliva-based lithium sensors, are reshaping the future landscape. Anti-inflammatory agents, neurosteroids, and compounds modulating oxidative stress are emerging as promising candidates. Additionally, medications targeting specific biological pathways implicated in bipolar pathophysiology, such as N-methyl-D-aspartate (NMDA) receptor modulators, phosphodiesterase inhibitors, and neuropeptides, are under investigation. Conclusions: Advances in pharmacogenomics will enable clinicians to predict individual responses and tolerability, minimizing trial-and-error prescribing. The future landscape may also incorporate digital therapeutics, combining pharmacotherapy with remote monitoring and data-driven adjustments. Ultimately, integrating innovative drug therapies with personalized approaches has the potential to enhance efficacy, reduce adverse effects, and improve long-term outcomes for individuals with bipolar disorder, ushering in a new era of precision psychiatry. Full article

Background: Despite significant advancements in diabetes care, many individuals with type 2 diabetes (T2D) do not receive optimal care and treatment. Digital interventions promoting behavioral changes have shown promising long-term results in supporting healthier lifestyles but are not implemented in most healthcare offerings, maybe due to lack of general practice support and collaboration. This study evaluates the efficacy of the Digital, Individualized, and Collaborative Treatment of T2D in General Practice Based on Decision Aid (DICTA), a randomized controlled trial integrating a patient-centered smartphone application for lifestyle support in conjunction with a clinical decision support (CDS) tool to assist general practitioners (GPs) in optimizing antidiabetic treatment. Methods: The present randomized controlled trial aims to recruit 400 individuals with T2D from approximately 70 GP clinics (GPCs) in Denmark. The GPCs will be cluster-randomized in a 2:3 ratio to intervention or control groups. The intervention group will receive one year of individualized eHealth lifestyle coaching via a smartphone application, guided by patient-reported outcomes (PROs). Alongside this, the GPCs will have access to the CDS tool to optimize pharmacological decision-making through electronic health records. The control group will receive usual care for one year, followed by the same intervention in the second year. Results: The primary outcome is the one-year change in estimated ten-year cardiovascular risk, assessed by SCORE2-Diabetes calculated from age, smoking status, systolic blood pressure, total and high-density lipoprotein cholesterol, age at diabetes diagnosis, HbA1c, and eGFR. Conclusions: If effective, DICTA could offer a scalable, digital-first approach for improving T2D management in primary care by combining patient-centered lifestyle coaching with real-time pharmacological clinical decision support. Full article

Background and Clinical Significance: Serratus Anterior Muscle Pain Syndrome (SAMPS) is an underdiagnosed cause of anterior chest wall pain, often attributed to myofascial trigger points of the serratus anterior muscle (SAM) or dysfunction of the Long Thoracic Nerve (LTN), leading to significant disability and affecting ipsilateral upper limb movement and quality of life. Current diagnosis relies on exclusion and physical examination, with limited treatment options beyond conservative approaches. This case report presents a novel approach to chronic SAMPS, successfully diagnosed using Sonoguided Digital Palpation (SDP) and treated with ultrasound-guided hydrodissection of the LTN using 5% dextrose in water (D5W) without local anesthetic (LA), in a patient where conventional treatments had failed. Case Presentation: A 72-year-old male presented with a three-year history of persistent left chest pain radiating to the upper back, exacerbated by activity and mimicking cardiac pain. His medical history included two percutaneous coronary interventions. Physical examination revealed tenderness along the anterior axillary line and a positive hyperirritable spot at the mid axillary line at the 5th rib level. SDP was used to visualize the serratus anterior fascia (SAF) and LTN, and to reproduce the patient’s concordant pain by palpating the LTN. Ultrasound-guided hydrodissection of the LTN was then performed using 20–30cc of D5W without LA to separate the nerve from the surrounding tissues, employing a “fascial unzipping” technique. The patient reported immediate pain relief post-procedure, with the pain reducing from 9/10 to 1/10 on the Numeric Rating Scale (NRS), and sustained relief and functional improvement at the 12-month follow-up. Conclusions: Sonoguided Digital Palpation (SDP) of the LTN can serve as a valuable diagnostic adjunct for visualizing and diagnosing SAMPS. Ultrasound-guided hydrodissection of the LTN with D5W without LA may provide a promising and safe treatment option for patients with chronic SAMPS refractory to conservative management, resulting in rapid and sustained pain relief. Further research, including controlled trials, is warranted to evaluate the long-term efficacy and generalizability of these findings and to compare D5W to other injectates. Full article

Total Knee Arthroplasty (TKA) is a well-established surgical intervention for the management of end-stage knee osteoarthritis. While the procedure is generally successful, postoperative rehabilitation remains a key determinant of long-term functional outcomes. Traditional rehabilitation protocols, particularly those requiring in-person clinical visits, often encounter limitations in accessibility, patient adherence, and personalization. In response, emerging sensor technologies have introduced innovative solutions to support and enhance recovery following TKA. This review provides a thematically organized synthesis of the current landscape and future directions of sensor-assisted rehabilitation in TKA. It examines four main categories of technologies: wearable sensors (e.g., IMUs, accelerometers, gyroscopes), smart implants, pressure-sensing systems, and mobile health (mHealth) platforms such as ReHub^® and BPMpathway. Evidence from recent randomized controlled trials and systematic reviews demonstrates their effectiveness in tracking mobility, monitoring range of motion (ROM), detecting gait anomalies, and delivering real-time feedback to both patients and clinicians. Despite these advances, several challenges persist, including measurement accuracy in unsupervised environments, the complexity of clinical data integration, and digital literacy gaps among older adults. Nevertheless, the integration of artificial intelligence (AI), predictive analytics, and remote rehabilitation tools is driving a shift toward more adaptive and individualized care models. This paper concludes that sensor-enhanced rehabilitation is no longer a future aspiration but an active transition toward a smarter, more accessible, and patient-centered paradigm in recovery after TKA. Full article

The 100-Day Mission, coordinated by the Coalition for Epidemic Preparedness Innovations (CEPI) and endorsed by significant international stakeholders, aims to shorten the timeframe for developing and implementing vaccines to 100 days after the report of a new pathogen. This ambitious goal is outlined as an essential first step in improving pandemic preparedness worldwide. This review highlights the mission’s implementation potential and challenges by examining it through the lens of low- and middle-income countries (LMICs), which often face barriers to equitable vaccine access. This article explores the scientific, economic, political, and social aspects that could influence the mission’s success, relying on lessons learned from previous pandemics, such as the Spanish flu, H1N1, and COVID-19. We also examined important cornerstones like prototype vaccine libraries, accelerated clinical trial preparedness, early biomarkers identification, scalable manufacturing capabilities, and rapid pathogen characterization. The review also explores the World Health Organization (WHO) Pandemic Agreement and the significance of Phase 4 surveillance in ensuring vaccine safety. We additionally evaluate societal issues that disproportionately impact LMICs, like vaccine reluctance, health literacy gaps, and digital access limitations. Without intentional attempts to incorporate under-resourced regions into global preparedness frameworks, we argue that the 100-Day Mission carries the risk of exacerbating already-existing disparities. Ultimately, our analysis emphasizes that success will not only rely on a scientific innovation but also on sustained international collaboration, transparent governance, and equitable funding that prioritizes inclusion from the beginning. Full article

Background: The gut microbiota is increasingly recognized as a key modulator in obesity management, influencing host energy balance, lipid metabolism, and inflammatory pathways. With obesity prevalence continuing to rise globally, dietary interventions that promote beneficial microbial shifts are essential for enhancing weight loss outcomes and long-term health. Objective: This study investigated the effects of the multicomponent Weight Loss Maintenance 3 Phases Program (WLM3P), which integrates caloric restriction, a high-protein low-carbohydrate diet, time-restricted eating (10h TRE), dietary supplementation (prebiotics and phytochemicals), and digital app-based support on gut microbiota composition compared to a standard low-carbohydrate diet (LCD) in adults with obesity. The analysis focused exclusively on the 6-month weight loss period corresponding to Phases 1 and 2 of the WLM3P intervention. Methods: In this sub-analysis of a randomized controlled trial (ClinicalTrials.gov Identifier: NCT04192357), 58 adults with obesity (BMI 30.0–39.9 kg/m²) were randomized to the WLM3P (n = 29) or LCD (n = 29) groups. Stool samples were collected at baseline and 6 months for 16S rRNA sequencing. Alpha and beta diversity were assessed, and genus-level differential abundance was determined using EdgeR and LEfSe. Associations between microbial taxa and clinical outcomes were evaluated using regression models. Results: After 6-month, the WLM3P group showed a significant increase in alpha diversity (p = 0.03) and a significant change in beta diversity (p < 0.01), while no significant changes were observed in the LCD group. Differential abundance analysis revealed specific microbial signatures in WLM3P participants, including increased levels of Faecalibacterium. Notably, higher Faecalibacterium abundance was associated with greater reductions in fat mass (kg, %) and visceral adiposity (cm²) in the WLM3P group compared to LCD (p < 0.01). Conclusions: These findings suggest a potential microbiota-mediated mechanism in weight loss, where Faecalibacterium may enhance fat reduction effectiveness in the context of the WLM3P intervention. Full article

Background/Objectives: Manual therapy techniques, including mobilization and manipulation, are commonly used for chronic low back pain (CLBP), with clinical guidelines recommending their use. This study aimed to compare the immediate hypoalgesic effects of mobilization and manipulation in patients with non-specific CLBP, evaluating their impact on pain sensitivity and range of motion. Methods: A cross-over randomized controlled trial was conducted with 27 participants with non-specific CLBP. Participants received either mobilization or manipulation on two different intervention days. Outcome measures included pressure pain thresholds (PPTs) assessed with a digital algometer, pain intensity using a numeric rating scale, and lumbar range of motion (ROM) measured with a digital inclinometer. Results: The results indicated no statistically significant differences between mobilization and manipulation for any outcome measures (all p > 0.05). However, significant within-intervention improvements were observed, including pain reduction, increased PPTs, and enhanced ROM of the lower back. Conclusions: Our findings suggest that both mobilization and manipulation provide similar immediate benefits for patients with CLBP. The choice between these techniques should be based on therapists’ clinical reasoning and individualized risk stratification, considering the potential benefits and risks of each approach for a specific patient. Full article

Background: Hypotension following epidural labor analgesia (ELA) is its most common complication, affecting approximately 20% of patients and posing risks to both maternal and fetal health. As digital tools and predictive analytics increasingly shape perioperative and obstetric anesthesia practices, real-world implementation data are needed to guide their integration into clinical care. Current monitoring practices rely on intermittent non-invasive blood pressure (NIBP) measurements, which may delay recognition and treatment of hypotension. The Hypotension Prediction Index (HPI) algorithm uses continuous arterial waveform monitoring to predict hypotension for potentially earlier intervention. This clinical trial evaluated the feasibility, acceptability, and efficacy of continuous HPI-guided treatment in reducing time-to-treatment for ELA-associated hypotension and improving maternal hemodynamics. Methods: This was a prospective randomized controlled trial design involving healthy pregnant individuals receiving ELA. Participants were randomized into two groups: Group CM (conventional monitoring with NIBP) and Group HPI (continuous noninvasive blood pressure monitoring). In Group HPI, hypotension treatment was guided by HPI output; in Group CM, treatment was based on NIBP readings. Feasibility, appropriateness, and acceptability outcomes were assessed among subjects and their bedside nurse using the Acceptability of Intervention Measure (AIM), Intervention Appropriateness Measure (IAM), and Feasibility of Intervention Measure (FIM) instruments. The primary efficacy outcome was time-to-treatment of hypotension, defined as the duration between onset of hypotension and administration of a vasopressor or fluid therapy. This outcome was chosen to evaluate the clinical responsiveness enabled by HPI monitoring. Hypotension is defined as a mean arterial pressure (MAP) < 65 mmHg for more than 1 min in Group CM and an HPI threshold < 75 for more than 1 min in Group HPI. Secondary outcomes included total time in hypotension, vasopressor doses, and hemodynamic parameters. Results: There were 30 patients (Group HPI, n = 16; Group CM, n = 14) included in the final analysis. Subjects and clinicians alike rated the acceptability, appropriateness, and feasibility of the continuous monitoring device highly, with median scores ≥ 4 across all domains, indicating favorable perceptions of the intervention. The cumulative probability of time-to-treatment of hypotension was lower by 75 min after ELA initiation in Group HPI (65%) than Group CM (71%), although this difference was not statistically significant (log-rank p = 0.66). Mixed models indicated trends that Group HPI had higher cardiac output (β = 0.58, 95% confidence interval −0.18 to 1.34, p = 0.13) and lower systemic vascular resistance (β = −97.22, 95% confidence interval −200.84 to 6.40, p = 0.07) throughout the monitoring period. No differences were found in total vasopressor use or intravenous fluid administration. Conclusions: Continuous monitoring and precision hypotension treatment is feasible, appropriate, and acceptable to both patients and clinicians in a labor and delivery setting. These hypothesis-generating results support that HPI-guided treatment may be associated with hemodynamic trends that warrant further investigation to determine definitive efficacy in labor analgesia contexts. Full article

Background. Digital dentistry continues to evolve, offering improved accuracy, efficiency, and patient experience across various prosthodontic procedures. Many previous reviews have focused on digital applications in prosthodontics. But the use of a fully digital workflow for full-arch implant-supported prostheses in edentulous patients remains an emerging and underexplored area in the literature. Objective. This article presents a comprehensive methodological review of the digital workflow in full-arch implant-supported rehabilitation. It follows a structured literature exploration and synthesizes relevant technological processes from patient assessment to prosthetic delivery. Methods. The relevant literature was retrieved from the PubMed database on 20 June 2024, to identify the most recent and relevant studies. A total of 22 articles met the eligibility criteria and were included in the review. The majority included case and technical reports. Results. The review illustrates the integration and application of digital tools in implant dentistry, including cone-beam computed tomography (CBCT) exposure, intraoral scanning, digital smile design, virtual patients, guided surgery, and digital scanning. The key findings demonstrate multiple advantages of a fully digital workflow, such as reduced treatment time and cost, increased patient satisfaction, and improved interdisciplinary communication. Conclusions. Despite these benefits, limitations persist due to the low level of evidence, technological challenges, and the lack of standardized protocols. Further randomized controlled trials and long-term clinical evaluations are essential to validate the effectiveness and feasibility of a fully digital workflow for full-arch implant-supported rehabilitation. Full article

Background: The European League Against Rheumatism (EULAR), in collaboration with the European Scleroderma Trial and Research group (EUSTAR), published the first set of treatment recommendations for systemic sclerosis (SSc) in 2009, with subsequent updates in 2016 and 2023. Objectives: This study aimed to evaluate how rheumatologists’ clinical approaches to the treatment of SSc evolved following the 2016 update of the clinical management guidelines. Methods: Medication use for SSc was analyzed in a cohort of 378 patients. The patients were stratified based on enrollment before (233 patients) and after (145 patients) the guideline update, and medication usage was compared between the two groups. Results: Although all patients presented with Raynaud’s phenomenon (RP), only 35% received calcium channel blockers. Medications such as iloprost, phosphodiesterase type 5 (PDE-5) inhibitors, fluoxetine, and bosentan, recommended for the treatment of RP and digital ulcers, were not approved for SSc by the Republic Health Insurance Fund. Treatment for pulmonary arterial hypertension (PAH) was administered to only 16 patients (4.2%), including 2 who received bosentan, 10 who received PDE-5 inhibitors, and 4 who were treated with riociguat. The use of PDE-5 inhibitors increased following the 2016 update of the guidelines. Cyclophosphamide was consistently prescribed for interstitial lung disease (ILD), with an increased frequency observed after the guideline update. No significant differences were observed in the use of methotrexate for skin involvement, ACE inhibitors for scleroderma renal crisis, or antibiotics for gastrointestinal symptoms. Proton pump inhibitors (PPIs) were prescribed to 87.3% of patients with gastrointestinal involvement, with an increase in use of both PPIs and prokinetic agents following the guideline update. Conclusions: Rheumatologists’ adherence to the EULAR/EUSTAR guidelines varied considerably, with 25% to 100% of eligible patients receiving the recommended treatments. Concordance improved in the management of PAH, ILD, and gastrointestinal involvement after the 2016 guideline update. Full article

Background and Objectives: Bone regeneration (BR) is a cornerstone technique in reconstructive dental surgery, traditionally using either barrier membranes, titanium meshes, or perforated non-resorbable membranes to facilitate bone regeneration. Recent advancements in 3D technology, including CAD/CAM and additive manufacturing, have enabled the development of customized scaffolds tailored to patient needs, potentially overcoming the limitations of conventional methods. Materials and Methods: A scoping review was conducted according to the PRISMA guidelines. Electronic searches were performed in MEDLINE (PubMed), the Cochrane Library, Scopus, and Web of Science up to January 2025 to identify studies on digital technologies applied to bone augmentation. Eligible studies encompassed randomized controlled trials, cohort studies, case series, and case reports, all published in English. Data regarding digital workflows, software, materials, printing techniques, and sterilization methods were extracted from 23 studies published between 2015 and 2024. Results: The review highlights a diverse range of digital workflows, beginning with CBCT-based DICOM to STL conversion using software such as Mimics and Btk-3D^®. Customized titanium meshes and other meshes like Poly Ether-Ether Ketone (PEEK) meshes were produced via techniques including direct metal laser sintering (DMLS), selective laser melting (SLM), and five-axis milling. Although titanium remained the predominant material, studies reported variations in mesh design, thickness, and sterilization protocols. The findings underscore that digital customization enhances surgical precision and efficiency in BR, with several studies demonstrating improved bone gain and reduced operative time compared to conventional approaches. Conclusions: This scoping review confirms that 3D techniques represent a promising advancement in BR. Customized digital workflows provide superior accuracy and support for BR procedures, yet variability in protocols and limited high-quality trials underscore the need for further clinical research to standardize techniques and validate long-term outcomes. Full article

Background/Objectives: Childhood cancer, although relatively rare, has a profound impact on the quality of life of affected children and their families. Technological advances have facilitated the development of mobile applications (apps) aimed at enhancing symptom monitoring and improving communication with healthcare teams. This systematic review aimed to analyse the effect of mobile applications on the health of children with cancer, with a specific focus on health-related quality of life (HRQoL). Methods: A systematic review was conducted in accordance with PRISMA 2020 guidelines. Searches were performed in PubMed (Medline), CINAHL, Cochrane and Scopus databases using MeSH terms such as Smartphone, Mobile Applications, Child Health, Neoplasms, and Digital Health, with no date restrictions, and including studies published in English, Spanish or Portuguese. We included original research studies that examined the use of mobile apps in paediatric oncology patients. The search was completed in January 2025. Results: Of the 324 records initially identified, 14 studies (mainly pilot studies, early-phase clinical trials, and observational designs) met the inclusion criteria. Interventions commonly focused on symptom tracking (pain, nausea, fatigue), promoting treatment adherence, and delivering educational content. Several studies reported high user acceptance and a potential positive impact on HRQoL, particularly when gamification strategies were incorporated to sustain children’s engagement. Conclusions: Despite the preliminary nature and small sample sizes of most studies, mobile applications appear to be effective in supporting symptom management, communication, and health education in paediatric oncology. Their use may contribute to improvements in HRQoL. Further high-quality research involving younger children and diverse socio-cultural contexts is required to confirm their effectiveness. Full article

This review provides a comprehensive analysis of recent advancements in lower limb exoskeleton systems, focusing on applications, control strategies, hardware architecture, sensing modalities, human-robot interaction, evaluation methods, and technical innovations. The study spans systems developed for gait rehabilitation, mobility assistance, terrain adaptation, pediatric use, and industrial support. Applications range from sit-to-stand transitions and post-stroke therapy to balance support and real-world navigation. Control approaches vary from traditional impedance and fuzzy logic models to advanced data-driven frameworks, including reinforcement learning, recurrent neural networks, and digital twin-based optimization. These controllers support personalized and adaptive interaction, enabling real-time intent recognition, torque modulation, and gait phase synchronization across different users and tasks. Hardware platforms include powered multi-degree-of-freedom exoskeletons, passive assistive devices, compliant joint systems, and pediatric-specific configurations. Innovations in actuator design, modular architecture, and lightweight materials support increased usability and energy efficiency. Sensor systems integrate EMG, EEG, IMU, vision, and force feedback, supporting multimodal perception for motion prediction, terrain classification, and user monitoring. Human–robot interaction strategies emphasize safe, intuitive, and cooperative engagement. Controllers are increasingly user-specific, leveraging biosignals and gait metrics to tailor assistance. Evaluation methodologies include simulation, phantom testing, and human–subject trials across clinical and real-world environments, with performance measured through joint tracking accuracy, stability indices, and functional mobility scores. Overall, the review highlights the field’s evolution toward intelligent, adaptable, and user-centered systems, offering promising solutions for rehabilitation, mobility enhancement, and assistive autonomy in diverse populations. Following a detailed review of current developments, strategic recommendations are made to enhance and evolve existing exoskeleton technologies. Full article

Background/objectives: Racial and ethnic minority patients are underrepresented in cancer clinical trials (CCTs) and multilevel strategies are required to increase participation. This study describes barriers and facilitators to minority CCT participation alongside feedback on a multilevel intervention (MLI) designed to reduce participation barriers, as posited by the socioecological model (SEM). Methods: Interviews with Moffitt Cancer Center (MCC) physicians, community physicians, patients with cancer, community residents, and clinical research coordinators (CRCs) were conducted from June 2023–February 2024. Verbal responses were analyzed using thematic analysis and categorized into SEM levels. Mean helpfulness scores rating interventions (from 1 (not helpful) to 5 (very helpful)) were summarized. Results: Approximately 50 interviews were completed. Thematic findings confirmed CCT referral and enrollment barriers across all SEM levels. At the community level, MCC patients and community residents felt that community health educators can improve patient experiences and suggested they connect patients to social/financial resources, assist with patient registration, and provide CCT education. While physicians and CRCs reacted positively to all institutional-level tools, the highest scored tool simultaneously addressed CCT referral and enrollment at the institution (e.g., trial identification/referrals) and interpersonal level (communication platform for community and MCC physicians) (mean = 4.27). At the intrapersonal level, patients were enthusiastic about a digital CCT decision aid (mean = 4.53) and suggested its integration into MCC’s patient portal. Conclusions: Results underscore the value of conducting formative research to tailor interventions to target population needs. Our approach can be leveraged by future researchers seeking to evaluate MLIs addressing additional CCT challenges or broader health topics. Full article

Background/Objectives: Heart failure with preserved ejection fraction (HFpEF) has emerged as one of the most challenging syndromes in modern cardiology due to its complex pathophysiology, diagnostic ambiguity, and lack of effective targeted therapies. Unlike heart failure with reduced ejection fraction (HFrEF), HFpEF encompasses a highly heterogeneous patient population unified only by a preserved left ventricular ejection fraction (LVEF) ≥ 50%. This broad definition overlooks important biological and clinical differences, leading to inconclusive results in large-scale therapeutic trials and suboptimal patient outcomes. In recent years, advances in data-driven methodologies—such as unsupervised machine learning, cluster analysis, and latent class modeling—have enabled the identification of distinct HFpEF phenotypes. These phenotypes, often defined by demographic, clinical, hemodynamic, and biomarker profiles, exhibit differential prognoses and treatment responses. Methods: This systematic review synthesizes findings from 20 studies published between 2010 and 2025, examining phenotypic classification strategies and their clinical implications. Results: Despite methodological variation, several recurring phenotypes emerge, including metabolic–obese, frail–elderly, atrial-fibrillation-dominant, cardiorenal, and pulmonary hypertension/right-heart phenotypes. Each presents a distinct pathophysiological mechanism and risk profile, highlighting the inadequacy of current one-size-fits-all treatment approaches. The review also explores the prognostic value of phenotypes, the impact of phenotypic variation on treatment efficacy, and the methodological challenges that hinder translation into clinical practice—such as inconsistent input variables, lack of external validation, and limited integration with real-world data. Conclusions: Ultimately, the findings underscore the need for a paradigm shift from ejection fraction-based classification to phenotype-guided management in HFpEF. Embracing a precision medicine framework could enable personalized treatment strategies, improve clinical trial design, and enhance outcomes for this diverse patient population. The review concludes by outlining future directions, including the development of standardized phenotyping algorithms, integration of multi-omic and digital health data, and the implementation of pragmatic, phenotype-stratified clinical trials. Full article