Search Results (419)

Background: Atherosclerotic heart disease (AHD) remains a leading cause of global mortality and a major driver of fatal cardiac syndromes. Ischemic myocardial injury from AHD can lead to ventricular remodeling and myocyte loss, progressing to heart failure (HF) and, in advanced stages, cardiogenic shock (CS). However, long-term national mortality trends for deaths involving the combined burden of AHD, HF, and CS remain insufficiently characterized. Methods: Mortality data from 1999 to 2023 were obtained from the CDC WONDER Multiple Cause of Death database. Deaths involving CS (ICD-10 R57.0), HF (I50, I50.1, I50.9), and AHD (I25.1) in adults were identified. Age-adjusted mortality rates (AAMRs) per 1,000,000 population were calculated and stratified by sex, race/ethnicity, and geographic region. Temporal trends were analyzed using Joinpoint regression to estimate annual percent changes (APCs) and average annual percent changes (AAPCs). Autoregressive integrated moving average (ARIMA) modeling was used to forecast mortality trends through 2035. Results: A total of 15,631 deaths were attributed to AHD-associated HF and CS during the study period. Overall AAMRs increased significantly (AAPC 3.75%; 95% CI 3.32–4.29; p < 0.01). Mortality rates declined between 1999 and 2006 (APC −7.55%; 95% CI −13.15 to −5.23; p < 0.01), increased modestly from 2006 to 2013 (APC 3.94%; 95% CI −1.47 to 8.91), and rose sharply from 2013 to 2023 (APC 12.33%; 95% CI 11.27–14.46; p < 0.01). Males had higher AAMRs than females in 2023 (9.26 vs. 3.39 per 1,000,000). Non-Hispanic White individuals accounted for the highest number of deaths (11,878), followed by non-Hispanic Black individuals (1708), while non-Hispanic American Indian populations had the lowest counts (39). Regionally, the West (7.31) and South (5.92) exhibited the highest final AAMRs. State-level AAMRs ranged from 2.49 in Minnesota to 8.27 in Nevada. Conclusions: Mortality involving AHD, HF, and CS has risen substantially in the United States since 2013, with marked demographic and geographic disparities. These findings highlight a growing burden of advanced ischemic heart disease and heart failure and underscore the need for earlier intervention and improved access to advanced HF therapies to prevent progression to cardiogenic shock and death. Full article

Background: Wearable sensing technologies enable continuous monitoring of physiological states in athletes, yet age-related differences in autonomic and mechanical load among professional soccer players remain insufficiently characterized. This study investigated whether heart rate variability (HRV) indices and accelerometry-derived physical load differ between younger and older professional players during routine morning training sessions. Methods: Fourteen male professional soccer players were monitored using a wrist-worn biosensor. Participants were divided into two age groups: Group A (≤23 years, n = 7) and Group B (≥24 years, n = 7). The device was attached at 08:30 and recorded tri-axial acceleration and cardiac signals continuously until 11:30 (≈3 h). Extracted metrics included root mean square of successive differences (RMSSD), percentage of NN intervals differing by more than 50 ms (pNN50), heart rate recovery (HRR), maximum heart rate, and total beat count. Group differences and position-based differences were evaluated. Results: Accelerometry-based physical load showed no significant difference between age groups. In contrast, HRV indices demonstrated age-related divergence: RMSSD was significantly higher in Group A compared to Group B (p = 0.031), suggesting greater parasympathetic activity in younger players. Total beat count was significantly higher in Group B (p = 0.015). pNN50 showed no group difference (p = 0.918). Pre- and post-session HRR did not differ significantly between groups, whereas maximum heart rate was significantly higher in Group A (p = 0.0017). Position-based comparisons revealed no consistent differences across metrics. Conclusions: Although mechanical load was comparable between age groups, autonomic markers—particularly RMSSD—indicated higher parasympathetic modulation in younger professional players. These findings align with established sports physiology literature but provide preliminary evidence derived from real-world data collected in professional soccer athletes using a compact wrist-worn biosensor. The results support the utility of wearable HRV monitoring for age-related physiological profiling in elite sports environments. Full article

Background: Hypertrophic cardiomyopathy (HCM) is the most common monogenic cardiac disorder (prevalence 1:500), a major substrate of sudden cardiac death (SCD) in adolescents and young adults, and is modulated by regulatory mechanisms including non-coding RNAs (ncRNAs) such as microRNAs (miRNAs), long non-coding RNAS (lncRNAs) and circular RNAs (circRNAs), which act as epigenetic modulators and potential biomarkers. Methods: The study involves a PRISMA-based systematic review of 989 records from PubMed, Scopus, Embase, Web of Science and Cochrane, including 96 studies evaluating ncRNAs as diagnostic, prognostic, genotype-specific or mechanistic markers in clinically/genetically confirmed HCM. Human biomarker studies (circulating/tissue ncRNAs) were analyzed separately from experimental models (human myocardium, animal models, iPSC-derived cardiomyocytes, cardiac organoids). Results: Key findings include upregulated miR-29a, miR-21 and miR-133a in HCM plasma/tissue (correlating with hypertrophy/fibrosis), miR-499a-5p as an MYH7-specific marker, and miR-208b-3p/miR-155 associated with MYBPC3-related HCM. Pro-hypertrophic lncRNAs (e.g., NEAT1, UCA1), fibrotic lncRNAs (e.g., MIAT) and protective/mitochondrial circRNAs (e.g., circZFPM2) contribute to ceRNA networks linking hypertrophy, fibrosis, mitochondrial dysfunction and arrhythmic remodeling. Multi-ncRNA panels have shown discriminatory performance between HCM and selected phenocopies, while some signatures have been associated with atrial fibrillation and composite cardiac outcomes; however, these findings remain heterogeneous and require independent validation. Conclusions: NcRNAs are biologically relevant regulators of HCM and represent promising candidates for mechanistic investigation, biomarker development and, potentially, therapeutic targeting. Current clinical evidence remains insufficient to support their incorporation into established SCD risk prediction models or their use as standalone diagnostic tools, particularly given the heterogeneity of cohorts, sample sources and analytical approaches. Their potential forensic relevance is also exploratory: ncRNA profiling may provide an additional molecular layer for the characterization of cardiomyopathic substrates in unexplained SCD, but its specificity, post-mortem stability and incremental value over conventional autopsy, histopathology and molecular autopsy remain unestablished. Dedicated longitudinal clinical and forensic studies are required before ncRNAs can be considered for routine clinical or post-mortem application. Full article

Background: Diabetic retinopathy (DR) is the most prevalent microvascular complication of type 2 diabetes mellitus (T2DM) and a recognised marker of systemic vascular injury. Whether DR—graded independently by two experienced ophthalmologists as part of routine institutional care—is independently associated with concurrent nephropathy (urine albumin-to-creatinine ratio [UACR] ≥ 30 mg/g) and subclinical cardiac stress (N-terminal pro-B-type natriuretic peptide [NT-proBNP] ≥ 125 pg/mL) remains insufficiently examined. Methods: Retrospective cross-sectional study of 401 T2DM adults who underwent dilated fundus examination independently graded by two board-certified ophthalmologists (each ≥ 10 years’ experience in diabetic eye disease) using ETDRS-based classification. Inter-physician agreement was quantified by Cohen’s weighted kappa. The primary composite outcome was concurrent nephropathy and subclinical cardiac stress. Multivariable logistic regression adjusted for age, sex, HbA1c, diabetes duration, eGFR, hypertension, and pharmacological treatments. Results: The composite outcome was present in 120 (64.2%) DR-positive vs. 14 (6.5%) DR-negative patients (crude OR: 25.59 (13.78–47.51); p < 0.001; fully adjusted OR: 21.49 (11.02–41.81); p < 0.001). Inter-physician agreement was high (Cohen’s weighted κ = 0.88; 95% CI: 0.83–0.93). Nephropathy alone was found in 164 (87.7%) vs. 76 (35.5%) patients (OR: 12.95 (7.71–21.75); p < 0.001), and elevated NT-proBNP in 137 (73.3%) vs. 39 (18.2%) patients (OR: 12.29 (7.65–19.76); p < 0.001). A significant trend across DR severity grades was observed (p for trend < 0.001), although the gradient was not strictly monotonic. ROC AUC = 0.837 (95% CI: 0.784–0.860). Conclusions: Ophthalmologist-graded DR was independently associated with the concurrent presence of albuminuria and elevated NT-proBNP in T2DM. Because the design is cross-sectional, these findings describe association rather than prediction or causation. They generate the hypothesis that retinal grading may help flag patients in whom cardiorenal biomarker assessment is worth considering, but prospective validation is required before any screening application. Full article

Transthyretin cardiac amyloidosis (ATTR-CA) is an increasingly recognized cause of cardiac dysfunction in adults, resulting from extracellular deposition of misfolded transthyretin fibrils and progressive myocardial impairment. Clinical expression and diagnostic yield differ substantially between sexes, contributing to systematic underdiagnosis in women, who often present with subtler myocardial remodeling, heart failure with preserved ejection fraction (HFpEF)–dominant phenotypes, and nonspecific systemic manifestations that fall below conventional diagnostic thresholds, particularly in early disease stages. Female patients, particularly those with ATTRwt, tend to present at older ages and more frequently show HFpEF-dominant phenotypes and nonspecific extracardiac manifestations. Carpal tunnel syndrome (CTS) is an important extracardiac red flag for ATTR-CM, but its interpretation in women requires caution because of the high background prevalence of idiopathic CTS in the general population. Evidence also suggests sex-related differences in diastolic function, right ventricular involvement, and overall progression. Despite these biological and phenotypic distinctions, women are markedly underrepresented in trials of disease-modifying therapies, limiting conclusions about sex-specific treatment effects and leaving uncertainty about whether current pharmacologic interventions provide comparable benefit. Hormonal influences, genetic background, and age-related mechanisms, comorbidities, and diagnostic pathways may contribute to the distinctive female phenotype, but underlying mechanisms remain insufficiently defined. This narrative review examines sex-associated differences in ATTR-CA, focusing on mechanisms of underdiagnosis, principal clinical and imaging features, and implications for therapeutic response, with the goal of improving diagnostic accuracy, guiding individualized management, and ultimately enhancing outcomes for women and all affected patients worldwide in clinical practice. Full article

Cardiovascular diseases (CVDs) remain the leading cause of mortality worldwide, driving the need for reliable tools for early risk prediction. Artificial intelligence (AI) applied to electrocardiograms (ECGs) has shown strong predictive performance for future cardiac events, yet its clinical adoption remains limited by the lack of transparency and trust associated with black-box models. This systematic review examines recent advances in AI-based cardiovascular prediction, focusing on the combined challenges of multi-modal data fusion and clinically actionable explainability. Following PRISMA 2020 guidelines, we analyzed 65 peer-reviewed studies published between 2018 and 2025, identified through a systematic search of PubMed, IEEE Xplore, Web of Science, Scopus, ACM Digital Library, and Google Scholar. The reviewed literature reveals that while most AI-ECG models achieve high predictive accuracy, typically AUC 0.85–0.95, the majority rely on post hoc explainability techniques that offer limited clinical insight, and 61.5% of included studies implement no explainability method at all. External validation remains critically underutilized, performed by only 12.3% of studies, and multi-modal approaches integrating ECG data with electronic health records, biomarkers, or genomics represent only 27.7% of the reviewed literature. While these multi-modal models demonstrate improved contextualization and predictive performance, they remain insufficiently validated and inconsistently interpretable. Among studies employing XAI techniques, attention mechanisms were the most prevalent approach (28% of XAI studies), followed by saliency maps (20%), SHAP (16%), and LIME (8%). Only 9.2% of studies were prospective or clinical trials, underscoring the gap between algorithmic development and real-world clinical deployment. Applying a pre-specified four-level clinical actionability scoring framework (Level 0–3), we found that the majority of studies (61.5%) scored at Level 0 (no actionability), with only 9.2% reaching Level 3 (demonstrated clinical impact), confirming that the clinical translation gap extends beyond trial design to encompass the broader absence of clinically contextualised evaluation of AI-ECG systems. This review highlights a persistent and critical gap between predictive performance and clinical usability, and outlines four key directions for developing AI-ECG systems that can better support trustworthy clinical decision-making: (1) developing inherently interpretable architectures, (2) advancing unified multi-modal fusion and explanation frameworks, (3) establishing standardized benchmarks for explainability evaluation, and (4) conducting robust prospective validation measuring real-world patient outcomes. Full article

Taxilli Herba (Sangjisheng) is a hemi-parasitic medicinal plant whose quality is intrinsically linked to its host species. While previous reviews have extensively summarized its chemical constituents and pharmacological activities, a systematic understanding of how host trees dictate its quality and safety remains largely fragmented. This review bridges this gap by proposing a “host-governed quality paradigm.” By integrating historical records with modern scientific findings, we critically evaluate the molecular mechanisms underlying host–parasite interactions and their impact on medicinal quality. We highlight that host species influence Taxilli Herba across three critical dimensions: (i) chemical composition, comprising both intrinsic bioactive compounds and host-derived metabolites; (ii) toxicity profile, where even hosts lacking cardiac glycosides may pose potential safety hazards; and (iii) pharmacological activity, where host identity modulates therapeutic potency and traditional medicinal properties (e.g., “cold” vs. “warm” nature). Importantly, we highlight that the cardiac glycoside test specified in the current Chinese Pharmacopoeia is insufficient to ensure the safety of Sangjisheng derived from diverse hosts. To address these challenges, we propose a host-governed quality paradigm comprising four pillars: (1) mechanistic studies on host–parasite interactions; (2) revision of pharmacopeial standards to restrict approved sources; (3) promotion of standardized cultivation using safe host species (e.g., Morus alba); and (4) stringent quality control for edible and medicinal applications. This framework aims to ensure the safety, efficacy, and sustainable use of Sangjisheng in clinical practice. Full article

Extracorporeal cardiopulmonary resuscitation (ECPR) has emerged as a promising strategy for selected patients with refractory cardiac arrest, improving survival and the likelihood of favorable neurological outcomes. However, neurological prognostication in this setting remains highly challenging and insufficiently standardized. The pathophysiological complexity of ECPR, including global ischemia–reperfusion injury, altered cerebral perfusion, systemic inflammation, anticoagulation and prolonged sedation, limits the reliability of conventional post-cardiac arrest prognostic tools. This narrative review provides a focused and clinically oriented synthesis of current evidence on brain injury and neuroprognostication in patients undergoing veno-arterial extracorporeal membrane oxygenation (V-A ECMO) for cardiac arrest. Key determinants of neurological outcome across pre-ECMO and peri-resuscitation phases are examined, alongside the role and limitations of multimodal monitoring strategies, including neurological examination, electroencephalography, neuroimaging, cerebral oximetry and circulating biomarkers. Particular attention is given to the timing of prognostication and the risk of premature or inaccurate predictions leading to self-fulfilling prophecies. Emerging data suggest that neurological recovery in ECPR patients may be delayed, supporting a more cautious and time-adapted approach. A pragmatic, multimodal framework for neurological assessment in this population is outlined. By addressing current gaps and proposing a structured approach, this review aims to inform clinical decision making and contribute to improved neurologically meaningful survival in ECPR-treated cardiac arrest. Full article

Cardiac myosin-binding protein C (cMyBP-C) is a cardiac-restricted sarcomeric protein; after cardiomyocyte injury, circulating intact cMyBP-C and/or cMyBP-C fragments, collectively referred to here as the cMyC biomarker signal, appear rapidly in blood. In suspected acute coronary syndrome (ACS), its most important potential role is not as another marker of injury but as a decision-enhancing biomarker beyond symptoms, electrocardiography, cardiac troponin T and I concentrations measured with high-sensitivity assays (hs-cTnT and hs-cTnI), time from pain onset, and pre-test probability. This narrative review separates three clinical tasks frequently conflated in the biomarker literature: diagnosis of acute myocardial infarction, emergency-department triage, and prediction of short-term or post-infarction risk. We integrate cMyBP-C sarcomeric architecture, N-terminal regulatory biology, phosphorylation, proteolysis, circulating fragments, assay epitopes, analytical stability, diagnostic algorithms, point-of-care testing, ST-segment elevation myocardial infarction reperfusion biology, and major confounders including renal dysfunction, heart failure, age, sex, and chronic ventricular remodeling. Current evidence supports further evaluation of cMyC as an adjunct in early presenters and accelerated diagnostic pathways. However, diagnostic safety and efficacy have not been consistently reproduced across platforms and populations, and external validation—particularly of rule-out performance—remains insufficient for routine clinical use. Recurrent injury assessment and post-infarction risk phenotyping remain promising but incompletely validated applications. Before guideline adoption, cMyC needs phenotype-specific, multicenter implementation trials demonstrating incremental net benefit, cost-effectiveness, and patient-level safety compared with contemporary hs-cTnT- and hs-cTnI-based clinical decision algorithms. Full article

Cardiac contractility modulation (CCM) is an implantable device-based therapy that delivers biphasic, non-excitatory electrical signals to the ventricular myocardium during the absolute refractory period. By enhancing contractile performance without inducing depolarization or altering ventricular activation, CCM acts as bioelectronic myocardial conditioning. Current evidence supports its use in selected patients with symptomatic heart failure, reduced or mildly reduced left ventricular ejection fraction, narrow QRS duration, persistent symptoms despite guideline-directed medical therapy, and no indication for cardiac resynchronization therapy. In this population, CCM improves functional status and quality of life, whereas evidence for reductions in mortality or recurrent heart failure hospitalization remains less definitive. Whether CCM also reduces arrhythmic burden remains uncertain. Candidates for CCM frequently exhibit atrial and ventricular remodeling, neurohormonal activation, implantable cardioverter-defibrillators, and vulnerability to atrial fibrillation, ventricular arrhythmias, and device therapies. Mechanistically, CCM may render the failing myocardium less arrhythmogenic through coordinated effects on calcium handling, electromechanical remodeling, fibrosis-related substrate, contractile efficiency, and heart-failure stability. However, pivotal trials were not designed to assess arrhythmic endpoints, leaving the relationship between CCM and arrhythmic burden insufficiently characterized. This review summarizes CCM evidence, mechanistic rationale, available arrhythmic signals, device-related considerations, and future research priorities for prospective studies in this evolving field. Full article

Background: Increased placental thickness has been associated with adverse perinatal outcomes and fetal functional and structural abnormalities. However, whether marked third-trimester placental thickening is associated with a distinct maternal clinical profile compared with pregnancies with normal placental thickness remains insufficiently characterized. This study aimed to compare maternal characteristics, comorbidities, medication exposure, infection history, and fetal findings between pregnancies with marked placental thickening, defined as placental thickness ≥70 mm, and gestational-age-matched control pregnancies with a placental thickness <70 mm and no documented maternal or fetal abnormalities. Methods: This retrospective matched case–control study included singleton pregnancies referred for fetal echocardiography to a tertiary referral center in Łódź, Poland, between 1 January 2022 and 14 March 2025. Placental thickness was measured sonographically in a perpendicular plane from the chorionic plate to the basal plate, excluding the umbilical cord insertion site. Only anterior and/or fundal placentas assessed at ≥28 weeks of gestation were included. Among pregnancies with recorded third-trimester placental thickness measurements, 99 cases with placental thickness ≥70 mm were identified as the thick-placenta group. A control group of 99 pregnancies with placental thickness <70 mm was selected and matched for gestational age. Control pregnancies had no documented maternal disease, no fetal structural or functional abnormalities, and no exposure to the medications analyzed in this study. Maternal demographic characteristics, body mass index, comorbidities, infection history, obstetric history, and medication use were compared between groups. Continuous variables were compared using Welch’s t-test and the Mann–Whitney U test, and categorical variables were compared using Fisher’s exact test. Results: The study included 99 pregnancies with marked placental thickening and 99 control pregnancies with normal placental thickness. Gestational age at examination was comparable between groups, with a mean of 35.5 weeks in controls and 35.0 weeks in the thick-placenta group (p = 0.662, Welch’s t-test). Median gestational age was also not significantly different between groups (35.4 vs. 36.43 weeks; p = 0.340, Mann–Whitney U test). Mean placental thickness was significantly greater in the thick-placenta group than in controls (81.4 mm vs. 46.9 mm; p < 0.0001). Maternal age and anthropometric characteristics were comparable between groups, whereas BMI > 25 kg/m² was more common in the thick-placenta group. In contrast to the clinically healthy control group, maternal infection was documented in 100.0% of thick-placenta cases, hormonal treatment in 97.0%, history of COVID-19 in 52.5%, hypothyroidism in 44.4%, prior miscarriage in 37.4%, aspirin or anticoagulant use in 32.3%, gestational diabetes mellitus in 25.3%, and pregnancy-induced hypertension in 7.1%. All evaluated maternal clinical factors were significantly more common in the thick-placenta group than in controls. Fetal cardiac or extracardiac dysfunction was present in 68.7% of thick-placenta pregnancies. Conclusions: In this gestational-age-matched case–control study, pregnancies with marked third-trimester placental thickening showed a distinct maternal profile compared with healthy controls with normal placental thickness. Despite comparable gestational age, maternal age, and maternal anthropometric characteristics, the thick-placenta group demonstrated a significantly higher infectious, hormonal, metabolic, and endocrine burden. These findings indicate that, in this selected tertiary referral cohort, placental thickness ≥70 mm was associated with a higher burden of maternal clinical abnormalities and fetal functional findings. Rather than representing an independent marker of placental maladaptation or maternal-fetal risk, marked placental thickening should be interpreted as a clinically relevant ultrasound finding that may prompt careful review of maternal history and targeted fetal assessment. Prospective studies are needed to determine which maternal factors are independently associated with placental thickening and to clarify their relationship with fetal function and perinatal outcomes. Full article

Fetal growth restriction (FGR) has traditionally been attributed to placental insufficiency. However, accumulating evidence suggests that maternal cardiovascular maladaptation contributes to disease expression, clinical heterogeneity, and long-term maternal cardiovascular risk. To review maternal echocardiographic findings in pregnancies complicated by FGR, with or without preeclampsia and to explore the role of cardiovascular phenotyping in risk stratification and clinical management. Narrative review of the current literature, including observational studies, systematic reviews, meta-analyses, and expert consensus statements on maternal hemodynamics and echocardiographic assessment in FGR. FGR is associated with a maladaptive cardiovascular profile characterized by reduced cardiac output, increased systemic vascular resistance and adverse cardiac remodeling. Echocardiography frequently identifies subclinical myocardial dysfunction, including impaired diastolic function and reduced global longitudinal strain despite preserved ejection fraction. Distinct maternal cardiovascular phenotypes emerge across the FGR spectrum, ranging from high-risk hypodynamic, resistance-dominant phenotypes to intermediate and low-risk phenotypes with preserved hemodynamic adaptation. Integration of maternal cardiovascular assessment with fetal Doppler findings may improve risk stratification and support phenotype-guided surveillance and therapeutic decision-making. Persistent postpartum cardiovascular abnormalities further support the concept of pregnancy as a cardiovascular stress test and identify women at increased long-term cardiovascular risk. FGR should be viewed as the clinical manifestation of a complex maternal–placental–cardiovascular interaction rather than an isolated placental disorder. Maternal cardiovascular phenotyping has the potential to refine risk stratification, support hemodynamic-guided management, and identify women who may benefit from structured long-term cardiovascular surveillance. Full article

Background: Aortic insufficiency (AI) during long-term left ventricular assist device (LVAD) support creates a maladaptive recirculatory loop that impairs forward flow, increases left ventricular filling pressures, leading to progressive congestion, and accelerates right ventricular dysfunction. Surgical correction carries high risk, making transcatheter aortic valve implantation (TAVI) an alternative strategy, although outcomes are challenged by complex annular geometry and the absence of calcific anchoring. Methods: We performed a retrospective single-center analysis of consecutive LVAD-supported patients undergoing TAVI for native AI. Annular sizing was area-based with a predefined oversizing strategy of approximately 15–30%, adjusted to annular geometry. Balloon-expandable valves were implanted using controlled deployment under rapid pacing and temporary LVAD flow reduction. Outcomes were assessed according to VARC-3 definitions. Results: Fourteen patients underwent TAVI. The cohort demonstrated high anatomical complexity, including annular eccentricity (median 0.21 [IQR 0.19–0.23]), horizontal aorta (42.9%), and flared left ventricular outflow tract (LVOT) morphology (50%). Median annular area was 528 mm² (IQR 487–574), with area-derived diameter 25.9 mm (IQR 24.9–27.0). Mean oversizing was 21.9% (median 20.0%; range 15.1–30.3%). Technical and VARC-3 device success were achieved in 71.4%. Second valve implantation occurred in 28.6%. Procedural mortality was 0%. In-hospital mortality (21.4%) was related to low cardiac output and multi-organ dysfunction rather than device failure. No survivor had moderate or greater residual AI at discharge. Conclusions: In anatomically complex LVAD patients, an anatomy-driven balloon-expandable TAVI strategy achieved elimination of clinically significant AI with zero procedural mortality. In our interpretation, mortality reflected the advanced stage of heart failure at the time of intervention rather than acute device-related failure. Full article

Background and Objectives: Obstructive sleep apnea (OSA) is a prevalent sleep-related breathing disorder associated with increased cardiovascular morbidity and mortality. Continuous positive airway pressure (CPAP) is the standard treatment for OSA; however, its effects on cardiovascular outcomes remain incompletely established. This umbrella review synthesized and critically appraised the evidence regarding the effects of CPAP on surrogate, intermediate, and functional cardiovascular outcomes in adults with OSA. Materials and Methods: An umbrella review of systematic reviews and meta-analyses evaluating CPAP therapy in adults with OSA was conducted. A comprehensive literature search was performed in PubMed, Embase, and the Cochrane Library from database inception to 28 February 2026. Eligible reviews assessed cardiovascular outcomes, including blood pressure, cardiac function, autonomic function, cardiovascular biomarkers, and functional cardiovascular measures. Methodological quality was evaluated using AMSTAR 2, and the certainty of evidence for the main outcomes was assessed using the GRADE framework. Results: Thirty-eight systematic reviews and meta-analyses were included. CPAP therapy was consistently associated with reductions in systolic blood pressure (mean difference [MD] −4.8 mmHg) and diastolic blood pressure (MD −3.0 mmHg), with additional improvements in 24 h ambulatory blood pressure. Favorable effects were also observed for left ventricular ejection fraction (MD 3.27), left ventricular diastolic function (weighted mean difference [WMD] 0.22), and sympathetic nervous system activity, reflected by lower circulating noradrenaline levels (standardized mean difference [SMD] −1.10) in randomized controlled trials. Improvements in BNP/NT-proBNP concentrations and New York Heart Association functional class were reported among patients with heart failure, whereas no significant effect was observed on body mass index. The certainty of evidence ranged from low to moderate, and methodological confidence of the included reviews was predominantly moderate, low, or critically low. Conclusions: CPAP therapy was associated with improvements in several surrogate, intermediate, and functional cardiovascular outcomes in adults with OSA, particularly blood pressure, left ventricular function, and sympathetic activity. However, the certainty of evidence ranged from low to moderate, and substantial heterogeneity and methodological limitations warrant cautious interpretation. Current evidence remains insufficient to demonstrate a consistent reduction in major adverse cardiovascular events or cardiovascular mortality. Further high-quality randomized controlled trials with longer follow-up are needed to clarify the long-term cardiovascular impact of CPAP therapy. Full article

Historically framed as a behavioral addiction, gambling disorder (GD) has had its somatic dimension neglected by standard clinical evaluation. This is a narrative, hypothesis-generating review focusing on the somatic aspects of GD. Cross-sectional and prospective evidence increasingly shows a somatic phenotype distributed across four axes: cardiovascular (hypertension, angina, stroke, acute stress-induced cardiac events), metabolic (obesity, type 2 diabetes, chronic liver disease), sleep-related (insomnia, poor sleep quality, daytime sleepiness), and—as an emerging and insufficiently characterized dimension—neurological (clustering with seizures and frontal lobe epilepsy). Three candidate biological systems may translate this exposure into multi-system physiology: (i) a hyperreactive mesostriatal reward circuit hypothesized to sustain a behavioral cluster of smoking, hazardous alcohol use, low physical activity, and unhealthy diet; (ii) an integrated stress response postulated to shift from acute hyperreactivity to chronic basal cortisol blunting and reduced vagal tone; and (iii) putative alterations in peripheral neurotrophic signaling and frontal-callosal structure, marked by elevated peripheral brain-derived neurotrophic factor and by frontal-callosal white-matter alterations—with cumulative allostatic load serving as a conceptual integrating frame. We propose that GD can be a behaviorally driven systemic medical condition, warranting internal medicine involvement alongside addiction psychiatry. Within this framework, glucagon-like peptide-1 receptor agonists emerge as an exploratory therapeutic hypothesis warranting dedicated evaluation in GD, given their action on the mesolimbic reward substrate and phase 3 evidence in adjacent cardiometabolic, hepatic, and sleep conditions. Full article