The European Union Safe Hearts Plan provides an opportunity to strengthen cardiovascular prevention, early detection, treatment, and monitoring across Europe. This EFLM position paper argues that laboratory medicine must be recognized as a central component of its implementation. Reliable and harmonized laboratory data underpin cardiovascular risk assessment, diagnosis, therapeutic guidance, longitudinal monitoring, and evaluation of population outcomes. Beyond the minimum health-check dataset, tiered and personalized pathways should integrate established biomarkers, specialist testing, and validated emerging technologies. EFLM proposes five priorities: embedding laboratory expertise in governance; translating core testing into personalized pathways; expanding equitable access through quality-assured decentralized models; linking testing to clinical action and value-based financing; and accelerating responsible innovation while strengthening professional capability. By connecting screening with diagnosis, treatment, and measurable outcomes, laboratory medicine can provide the quality, interpretation, and data infrastructure required to transform the Safe Hearts Plan from policy ambition into equitable cardiovascular health gains across Europe.

Hypertrophic cardiomyopathy is the most common structural myocardial disease. Based on the literature, its estimated prevalence in the adult population is 1 : 500. It is distinguished by an exceptionally heterogeneous clinical presentation and a broad spectrum of disease trajectories. The disorder is recognised in only about 10% of the patients. In 90% of cases, patients remain undiagnosed, often due to the absence of symptoms. Hypertrophic cardiomyopathy is frequently the underlying cause of sudden cardiac death. In recent years, mortality of hypertrophic cardiomyopathy has declined due to improved device and pharmacotherapies. We aim to present the epidemiological significance of the disease in line with recent international guidelines, emphasizing the importance of diagnostic awareness and multiparametric evaluation. By promoting a cardiomyopathy mindset, we aim to raise awareness of clinical red flags. Early identification of patients with suspected hypertrophic cardiomyopathy in primary and cardiology outpatient care can facilitate prompt diagnosis and timely initiation of appropriate therapy. The review provides an overview of the diagnostic pathway recommended by the 2023 European Society of Cardiology Guidelines for the management of cardiomyopathies, describes the key components of the multiparametric, multimodal evaluation and presents clinical red flags. A significant proportion of the clinical red flags emphasized in the 2023 European Society of Cardiology Guidelines for the management of cardiomyopathies can be identified at lower levels of care and in primary care settings, thereby accelerating the diagnostic process and shortening the time to treatment. The diagnostic algorithm includes performing an ECG, assessing specific laboratory parameters, searching for extracardiac symptoms and conducting a comprehensive pedigree analysis focused on age-related phenotypic features. When clinical suspicion is high, advanced multimodal imaging should be included in addition to conventional imaging modalities. Orv Hetil. 2026; 167(38): 1495-1506.

BACKGROUND: Hypertonic sodium lactate (HSL) has demonstrated beneficial effects in experimental sepsis, improving hemodynamics, modulating inflammation, and supporting cellular metabolism. Nevertheless, prior studies have not specifically addressed microcirculation, despite its critical impairment during sepsis and the absence of targeted therapies. We evaluated the therapeutic effects of HSL in a in vivo resuscitated rat model (Male wistars) of cecal ligation and puncture (CLP), with a particular focus on microcirculatory function, followed by ex vivo investigation of sodium lactate on vascular reactivity. RESULTS: 10 h after CLP rats were infused with 0.9% NaCl or 11.2% HSL for 18 h before exploration. No difference was observed on arterial pressure, echocardiography and pressure-volume loops. HSL improved mesenteric perfusion (1126 [923-1300] vs. 816.5 [692-919] Perfusion Unit, p = 0.012) and TNF-α plasma levels (26.2 [22.8-37.1] vs. 42.6 [32.6-47.3] pg/mL, p = 0.001). Ex vivo, mesenteric artery reactivity experiments from healthy rats was tested with or without LPS-stimulation and glucose deprivation. Lactate dose-dependently restored LPS-impaired vasoconstriction, showing an independent effect on small arteries. In glucose deprivation conditions, HSL was able to restore vascular reactivity in normal or LPS-stimulated arteries. CONCLUSIONS: HSL specifically improved microcirculation and reduced systemic inflammation in septic rats. Moreover, lactate may act as an alternative to glucose in deprivation conditions. These benefits support its translational potential as a resuscitation fluid in sepsis.

BACKGROUND: Stroke is the second most common neurological complication in cancer patients after metastases. Cancer-associated coagulopathy (CAC) is an important mechanism of ischemic stroke in this population. We systematically reviewed the epidemiological, clinical, radiological, and pathophysiological features of CAC-related stroke, as well as associated biomarkers and treatment strategies. METHODS: A systematic search of PubMed/MEDLINE, Scopus, Cochrane Library, and Embase (2000-2025) was performed according to PRISMA 2020 guidelines. Search terms included "stroke", "cancer", "hypercoagulability", "coagulopathy", "disseminated intravascular coagulation", and "non-bacterial or marantic thrombotic endocarditis". Studies published in English or Spanish were included, whereas case reports and review articles were excluded. Data were synthesized qualitatively. RESULTS: Eighty-two studies met inclusion criteria. CAC-related stroke occurs predominantly within six months of cancer diagnosis and is strongly associated with advanced or metastatic disease and a high risk of early recurrence. Adenocarcinoma, particularly lung and pancreatic cancer, is the most frequently associated histological subtype. Proposed mechanisms include mucin-mediated platelet aggregation, tissue factor-driven coagulation, extracellular vesicles, and neutrophil extracellular trap formation, leading to thromboinflammation and platelet-rich thrombi. D-dimer is the biomarker most consistently associated with recurrence and mortality, while C-reactive protein, fibrinogen, CA-125, and transcranial Doppler microembolic signals show limited specificity. Characteristic imaging findings include multiple infarcts involving more than two vascular territories, particularly the 'three territories sign'. Low-molecular-weight heparin and direct oral anticoagulants are the most commonly used secondary prevention strategies. Thirty-day mortality rates range from 25 to 50%. CONCLUSIONS: CAC-related stroke is a distinct and underrecognized entity characterized by specific biological and radiological features and poor outcomes. Earlier recognition and optimized antithrombotic strategies may improve prognosis.

Cancer therapy-related cardiovascular toxicity (CTR-CVT) is an umbrella term for myocardial, vascular, electrical, and inflammatory complications of cytotoxic, targeted, immune, and radiation-based therapies. Cancer therapy-related cardiac dysfunction (CTRCD) is used here more narrowly for treatment-related myocardial dysfunction, typically identified by changes in left ventricular ejection fraction, global longitudinal strain, and/or cardiac biomarkers. The pathophysiology of CTR-CVT is multifactorial, but the implicated pathways should not be interpreted as equally causal. The dominant initiating mechanism is therapy-specific - anthracycline injury is best supported by topoisomerase IIβ (TOP2B)-mediated DNA damage with secondary mitochondrial and redox injury; HER2-directed toxicity by disruption of NRG1-ERBB2/ERBB4 survival signalling; fluoropyrimidine toxicity by coronary vasomotor dysfunction; VEGF-pathway inhibition by endothelial dysfunction and hypertension; immune checkpoint inhibitor toxicity by loss of immune tolerance; and radiotherapy injury by endothelial and microvascular damage with progressive fibrosis. Mitochondrial dysfunction, oxidative stress, inflammation, calcium dysregulation, apoptosis, and ferroptosis frequently act as downstream or amplifying pathways, although the clinical relevance of several regulated cell-death mechanisms remains incompletely established. Genetic susceptibility may further modify risk, but the strength of evidence differs among reported loci. Replicated pharmacogenetic associations, rare variants in established cardiomyopathy genes, and preliminary candidate-gene findings should therefore be considered separately. Most available studies remain limited by small cohorts, heterogeneous phenotyping, ancestry imbalance, and incomplete external replication. This review critically evaluates the hierarchy and strength of mechanistic and genetic evidence and discusses the extent to which these findings can currently inform risk stratification, surveillance, prevention, and treatment in precision cardio-oncology.

BACKGROUND: Pregnancy in Eisenmenger syndrome is associated with very high maternal and fetal risk. Complex congenital anatomy further complicates diagnosis and peripartum management, particularly where advanced imaging and pulmonary hypertension therapies are limited. Published evidence specifically addressing pregnancy with uncorrected DORV and Eisenmenger physiology remains sparse. CASE PRESENTATION: A 25-year-old primigravida at 34 weeks' gestation presented with progressive dyspnoea and generalized oedema. The available record documented a heart rate of 130 beats/min, respiratory rate of 25 breaths/min, oxygen saturation of 80% despite face-mask oxygen, a loud second heart sound, and a systolic murmur. Echocardiography showed large ventricular and atrial septal defects with colour Doppler flow, severe tricuspid regurgitation, and an estimated systolic pulmonary artery pressure of 85 mmHg. In the setting of marked hypoxaemia, these findings supported probable Eisenmenger physiology, although shunt direction and pulmonary vascular resistance were not documented. The aorta appeared to arise predominantly from the right ventricle, supporting suspected DORV, but the origin of both great arteries, VSD-great-artery relationship, and DORV subtype could not be defined. Following cardiology and obstetric assessment, labour was induced and vaginal delivery occurred four hours later. The liveborn neonate weighed 2.7 kg, had an initial Apgar score of 5, and was admitted to neonatal intensive care for stabilisation and monitoring. Postpartum haemoglobin fell to 7 g/dL and two units of packed red cells were transfused. The mother was monitored in intensive care for three days, transferred to cardiology on day 6, and discharged in stable condition on day 7. CONCLUSION: This report documents maternal survival through induced vaginal delivery and the first postpartum week, with a live birth, despite late recognition of probable Eisenmenger physiology and suspected complex congenital heart disease. The report does not establish the safety of vaginal delivery in Eisenmenger syndrome, and incomplete haemodynamic, anatomical, anaesthetic, and neonatal data limit causal interpretation.

In primary mitral valve regurgitation (MR), a failing valve induces volume overload (VO) of the left ventricle (LV), triggering neurohormonal responses and myocardial remodeling. Surgical valve repair is the most effective therapy for MR, improving symptoms and in some patients reversing cardiac hypertrophy. However, at least 20% of patients develop postoperative impairment of LV function with detrimental effects on long-term outcomes, with no known cause. Many MR patients receive pharmacological treatment to alleviate symptoms, with drugs that alter cardiac function, hemodynamics, and molecular pathways that influence cardiac remodeling. To support the advancement of medical management of MR, we developed a multiscale model of cardiac hypertrophy that links ventricular mechanics, cardiovascular hemodynamics, and cardiomyocyte molecular signaling. We calibrated the model using the Markov chain Monte Carlo algorithm, a machine learning method, to integrate data from 76 studies of experimental VO in animals. The model's predictions showed good agreement with experimental data on MR in dogs, including the chronic effects of four drugs on MR-induced hypertrophy. When simulating valve repair, our model suggests that full reversal of LV hypertrophy requires both the mechanical elimination of VO and the restoration of normal neurohormonal receptor activity. Finally, we explored selecting subsets of a large pool of pre-computed simulations to personalize model predictions for a small population or individual where insufficient data are available to refit the entire model.

CASE BACKGROUND: A 61-year-old man with a mechanical aortic valve developed Staphylococcus aureus bacteremia. His electrocardiogram showed sinus rhythm with atrioventricular Wenckebach and phase 4 left bundle branch block. He was subsequently found to have a peri-aortic root abscess that was likely eroding not only into the atrioventricular node, but into the left bundle fibers as well. TAKE-HOME MESSAGES: Phase 4 block is a pause-dependent conduction block that reflects underlying His-Purkinje system disease. During a critical pause, spontaneous phase 4 depolarization in a diseased His-Purkinje system allows more sodium channels to become inactivated, reducing excitability and resulting in transient conduction block.

BACKGROUND: Renal denervation (RDN) is a treatment option for resistant hypertension. CASE SUMMARY: We present a 64-year-old woman with medication intolerance secondary to mast cell activation syndrome who presented with uncontrolled hypertension and underwent bilateral RDN. Her systolic and diastolic recordings measured using Dinamap device (GE Healthcare), decreased from 151 ± 7.6 and 75 ± 4.1 mm Hg to 126 ± 4.5 and 66 ± 2.8 mm Hg, respectively, at 3 months after her procedure (both P < 0.05). DISCUSSION: We show that RDN can be used in patients with severe medication intolerance due to an autoimmune condition. We also highlight the utility of using office-automated testing, which allowed us to likely obtain more accurate multiple blood pressure readings over 15 minutes. TAKE-HOME MESSAGE: This report highlights RDN's efficacy in a patient unable to tolerate pharmacological antihypertensive therapy and highlights the clinical utility of using automated blood pressure readings.

BACKGROUND: Direct oral anticoagulants (DOACs) have simplified treatment for venous thromboembolism (VTE), but fewer mandatory monitoring visits may reduce opportunities for structured reassessment. We evaluated temporal changes in hospital-captured documentation of post-VTE care processes during the transition to DOAC-based treatment, including initial anticoagulation, clinical follow-up, laboratory monitoring, and selective imaging reassessment. METHODS: We conducted a single-center retrospective electronic health record cohort study using routinely collected vascular surgery outpatient and inpatient records from Peking University People's Hospital between 2009 and 2024. Patients with VTE-related evidence and a definable hospital-captured index date were included. Treatment eras were prespecified as 2009-2014, 2015-2019, and 2020-2024. The study-defined documentation measure comprised therapeutic anticoagulation within 14 days and clinical follow-up, laboratory monitoring, and selective VTE-related ultrasound or imaging reassessment within 15-90 days. RESULTS: Among 5998 patients with a definable hospital-captured index VTE-related event, the median age was 64.0 years, and 55.3% were female. Documented anticoagulation within 14 days increased from 34.1% in 2009-2014 to 58.0% in 2020-2024. Within 15-90 days, clinical follow-up was documented in 1483 patients (24.7%), laboratory monitoring in 366 (6.1%), and VTE-related ultrasound or imaging reassessment in 578 (9.6%). All four prespecified domains were documented in 149 patients (2.5%) overall and in 3.2% during 2020-2024. In multivariable analysis, the 2020-2024 era, pulmonary embolism presentation, and upper-extremity or catheter-related VTE were associated with higher odds of four-domain documentation completion. CONCLUSION: In this 16-year electronic health record cohort, hospital-captured documentation of early anticoagulation increased, whereas documentation of 90-day follow-up processes remained infrequent; incomplete documentation or care delivered outside the hospital system may have contributed. These findings highlight opportunities to strengthen continuity and traceability of post-VTE management through timely clinical review and individualized decisions regarding treatment duration, safety monitoring, and selective imaging when clinically indicated.

Functional neurological recovery after ischemic stroke remains a formidable challenge in neuroscience. Exosomes serve as pivotal mediators of intercellular communication, and the microRNAs (miRNAs) they carry, in particular, offer a promising "cell-free therapy" strategy for promoting neurological repair. This review systematically summarizes the multi-target mechanisms by which exosomal miRNAs regulate the neurovascular unit (NVU) and outlines technical strategies to enhance exosomal therapeutic efficacy through targeted modification and engineered cargo loading, with the aim of constructing a smart drug delivery system capable of precise navigation. Following the trajectory of "natural exosomes-engineered exosomes-clinical translation", this review addresses the core scientific question of how to transform exosomal miRNAs from natural messenger molecules with basic reparative activity into an intelligent therapeutic system for precise targeted delivery. It further explores precision exosome treatment models based on the pathological staging of stroke progression, and integrates single-cell, spatial transcriptomic, and multi-omics technologies to decode the "miRNA-cell source-target cell-signaling pathway" regulatory axis, thereby identifying candidate miRNA combinations with translational potential. Finally, this review provides an in-depth analysis of the core challenges in translating such nanotherapeutic strategies from the bench to the bedside, including manufacturing standardization, quality control, and potency assessment, with the aim of providing a theoretical basis for advancing exosomal miRNA therapies from mechanistic studies to precision stroke treatment.

BACKGROUND: Multi-vessel coronary artery disease (MVCD), defined as stenosis affecting ≥2 major coronary arteries, confers poor clinical outcomes in patients with coronary artery disease (CAD). Cytochrome P450 2C19 (CYP2C19) CYP2C19 participates in lipid metabolism and inflammatory regulation, which may be associated with individual variations in the severity of coronary artery lesions. This study aimed to explore the clinical and genetic factors associated with MVCD focusing on polymorphisms and chronic metabolic diseases. METHODS: This single‑center cross‑sectional study enrolled 4124 patients with angiographically confirmed CAD, who were divided into single‑vessel CAD (n=846) and MVCD (n=3278) groups. Baseline clinical data and genotypes were collected. The chi-square test, Hardy-Weinberg equilibrium test, and logistic regression analyses were performed for statistical evaluation. RESULTS: Higher prevalences of hypertension, type 2 diabetes mellitus, and dyslipidemia were observed in MVCD patients. CYP2C19*2 (rs4244285, 681G>A) and *3 (rs4986893, 636G>A) allele frequencies were markedly elevated in the MVCD group. Logistic regression analysis confirmed that hypertension (odds ratio (OR)=1.485, 95% confidence interval (CI): 1.267‑1.740, <0.001), T2DM (OR=2.441, 95% CI: 2.006‑2.970, <0.001), dyslipidemia (OR=1.313, 95% CI: 1.097‑1.572, =0.003), and CYP2C19 poor metabolizer (*2/*2, *2/*3 and *3/*3 genotypes) status (OR=1.744, 95% CI: 1.360‑2.237, <0.001) was independently associated with MVCD. The combined impaired CYP2C19 metabolic phenotype (intermediate (*1/*2 and *1/*3 genotypes) plus poor metabolizers) was also independently correlated with MVCD (adjusted OR=1.285, 95% CI: 1.095-1.508, =0.002). CONCLUSION: Clinical metabolic comorbidities and the combined impaired CYP2C19 metabolic phenotype are associated with MVCD. These findings may provide valuable reference for risk assessment of severe CAD.

The patatin-like phospholipase domain-containing protein 3 (Pnpla3) I148M polymorphism is a well-established genetic determinant of metabolic dysfunction-associated steatotic liver disease (MASLD), and emerging evidence links it to chronic kidney disease (CKD) and cardiovascular disease (CVD). However, the mechanisms underlying this relationship remain unclear. The goal of this study was to investigate the role of the Pnpla3 polymorphism on kidney function, blood pressure, and cardiac function in a mouse model carrying the identical human polymorphism. Male and female Pnpla3 knock-in and control C57BL/6 mice were fed either a normal sucrose diet (NSD) or a high sucrose diet (HSD) for 8 weeks. Glomerular filtration rate (GFR), blood pressure, cardiac, and vascular function were measured in each group. Renal cortical protein expression and kinome profiles were analyzed to identify pathways associated with hyperfiltration and renal injury. Pnpla3 mice exhibited increased renal sodium transporter levels and hyperfiltration, which was compounded by albuminuria in HSD mice. Pnpla3 mice were also hypertensive and exhibited impaired systolic function, consistent with pressure-overload-induced cardiac remodeling. Renal kinome profiling revealed sex- and diet-dependent alterations in serine/threonine kinases, primarily involving isoforms of protein kinase C (PKC), protein kinase A (PKA), cGMP-dependent protein kinase (PRKG), and calcium/calmodulin-dependent protein kinase (CaMK). Our findings suggest that Pnpla3 acts as a systemic cardio-renal risk allele that links metabolic dysregulation to progressive end-organ damage via renal kinase remodeling in a sex- and diet-dependent manner.

BACKGROUND: Permanent cardiac pacing in children is commonly indicated in high-grade atrioventricular block. These patients require long-term ventricular pacing (Vp), multiple device changes, and lead revisions. OBJECTIVES: To describe a single pediatric center's 30-year experience with permanent pacemaker implantation, focusing on long-term device-associated complications (DACs) and pacing-induced cardiomyopathy (PIC). METHODS: We conducted a retrospective observational study at KK Women's and Children's Hospital, Singapore. Patients with permanent pacemakers followed between January 1, 1994 and December 31, 2024 were included. Primary outcomes were DAC and PIC. RESULTS: Fifty-three patients underwent 113 pacemaker lead implantations; 51 (96.2%) had epicardial systems. Median follow-up was 12 years (interquartile range [IQR] 9-19 years). Median age at first pacemaker implantation was 16 months (IQR 2 months to 7.7 years). Congenital complete heart block was the most common indication (26 [49%]), followed by postoperative complete heart block (17 [32%]). Freedom from lead-associated complications was 85% and 83% at 5 and 10 years, respectively. Eight (15%) patients developed PIC. All patients with PIC had concomitant congenital heart disease (CHD) (8/8). CHD was present in 28.9% (13/45) of patients without PIC. Recovery of ventricular function occurred in two patients following pacing modification, but not in those managed with medical therapy alone. CONCLUSION: In this pediatric cohort with predominantly epicardial pacing systems, long-term DAC rates were acceptable. PIC occurred primarily in patients with CHD. These findings support careful pacing strategy selection and long-term surveillance in children requiring permanent pacing.

The classic organ-centric model of human physiology is rapidly giving way to a unified approach embracing the human body as an integrated network of bidirectional interorgan communication. The human microbiome serves as a fundamental mediator of this shift, regulating immune homeostasis, barrier integrity and metabolic signaling across organs. While the lung maintains a characteristic low-biomass microbiome in dynamic equilibrium, any disruption primes local and systemic immune responses contributing to disease. Beyond the well-described gut-lung axis, crosstalk between the lung and other distal organ systems is lesser recognized; however, increasingly acknowledged as a key under-appreciated contributor to respiratory disease including extrapulmonary complications. This review synthesizes current established evidence on axial connectivity of the lung microbiome across the gut, brain, skin, heart, kidney, and liver, and finds that such crosstalk is predominantly, though not exclusively gut-mediated. Direct lung-organ interactions are described for several axes; however, they remain preliminary. Across these lung-axial systems, common pathophysiological mechanisms emerge, including dysbiosis-induced depletion of microbial metabolites, immunomodulation, and barrier perturbations, all linking pulmonary disease with neuroinflammation, gastrointestinal deficits, and cardiac, renal, hepatic, and dermatological abnormalities. We assess how therapeutic modulation of interorgan systems offers promising avenues for improved risk stratification and novel therapeutics. Recognizing microbiome-mediated pulmonary-organ crosstalk represents an emerging conceptual framework in respiratory medicine, repositioning microbial communities as key modulators of extrapulmonary disease.

Lifestyle medicine (LM) provides a high-value framework for treating and potentially reversing chronic diseases, such as type 2 diabetes (T2D), obesity, cardiovascular diseases, and some cancers. Yet, the field of LM is still growing, and few examples exist of how to successfully implement LM into clinical care. This paper describes the implementation of 1:1 lifestyle medicine (LM) coaching visits for 45 patients with uncontrolled type 2 diabetes (T2D), (mean HbA1c 10.5%) and on multiple diabetes medications, at Cone Health's Reidsville Endocrinology practice in North Carolina, USA. In brief, during routine endocrinology visits, the lead physician of the LM program at Cone Health, who is trained in LM, identified patients with uncontrolled T2D where scheduling allowed him to fit in some additional time for coaching. Forty-five interested patients selected over a period of several weeks from Spring of 2022 to Fall of 2022 made the first cohort. During a typical LM encounter, immediately after addressing their referral concerns with a routine endocrinology consult, verbally consenting patients were personally invited to learn more about LM. They were provided with a packet of materials focused predominately on prescribing nutrition and exercise as treatment for chronic disease. The physician spent an additional 10-15 minutes with each verbally consenting patient to go through selected materials in the packet, focusing largely on nutrition and physical activity, and successfully billed for the additional time. The patients were encouraged to take the packet home for further learning and return to their next routine visits with questions and to engage in further coaching. Following this brief but intensely focused coaching session which was done in addition to the routine endocrinology visit, lifestyle medicine coaching was able to be incorporated into subsequent, routine endocrinology visits in many of the initially identified patients. The majority of these patients also accepted a referral to a dietitian in the same practice. This experience highlights a model for potentially integrating LM coaching into routine practice and, consistent with previous research, highlights the importance of a site champion for successful LM implementation. Future research is needed to formally assess the success of coaching visits, particularly in terms of assessing health outcomes in patients who engaged in the 1:1 coaching.

BACKGROUND: Older adults with hypertension commonly experience poor sleep quality and reduced health-related quality of life (HRQoL). Previous studies have mainly examined these associations using total scores, providing limited insight into interactions between specific symptom dimensions. This study aimed to construct a component- and dimension-level network linking sleep quality and HRQoL and to compare network differences across depressive-symptom status. METHODS: This study included 2,257 older adults. Sleep quality, HRQoL, and depressive symptoms were assessed using the B-PSQI, EQ-5D-5L, and PHQ-9, respectively. We estimated a component- and dimension-level network based on the EBICGlasso-regularized Gaussian graph model, calculated centrality and bridge centrality metrics, validated stability using the bootstrap method, and compared network differences between the depressive and non-depressive-symptom groups. RESULTS: The final network included 10 nodes and 32 non-zero edges among 45 possible edges, with a density of 0.711. The strongest associations were between sleep efficiency and sleep duration (SE-ST, 0.793), sleep interruption and subjective sleep quality (SW-SQ, 0.583), and self-care and usual activities (SC-UA, 0.560). Usual activities (UA) showed the highest strength centrality and expected influence, followed by subjective sleep quality (SQ), self-care (SC), and sleep efficiency (SE). Sleep efficiency had the highest bridge expected influence, followed by subjective sleep quality. Centrality indices demonstrated good stability (CS = 0.75). No significant differences were found in network structure (M = 0.224, > 0.05) or global strength (S = 0.119, > 0.05); repeated 1:1 subsampling broadly supported these findings. CONCLUSION: Sleep components and HRQoL dimensions formed a closely connected network in older adults with hypertension. Usual activities showed the highest centrality, while sleep efficiency and subjective sleep quality showed prominent cross-community. These domains may be useful for screening or hypothesis generation but should not be interpreted as confirmed intervention targets.

OBJECTIVES: Sleep disturbance is a prevalent issue among those who have experienced a stroke. The impact of gender on the prevalence of sleep disturbance within Asian stroke populations remains ambiguous. This research seeks to examine the prevalence of sleep disturbance among stroke survivors in Indonesia. METHODS: This quantitative prevalence analysis was based on the 2018 Indonesian Basic Health Research. A total of 7,147 stroke survivors who answered the sleep disturbance questions were included. The estimated prevalence and regression models were examined utilizing SPSS software. RESULTS: The total prevalence of sleep disturbance among stroke survivors in Indonesia was 28.4% (95% CI: 27.4%-29.4%). Females exhibited a greater frequency of sleep disturbance than males (34.4% versus 26.1%, respectively). When categorized by age group, both females and males exhibited a trend of rising sleep disturbance prevalence with time. Moreover, daily smoking, low educational attainment, rural residency, and insufficient physical activity were correlated with sleep disturbance symptoms in the male cohort. In females, the presence of comorbidities such as cardiovascular disease and asthma was associated with sleep disturbance. CONCLUSIONS: This study's findings revealed a significant prevalence of sleep disturbance among stroke survivors in Indonesia. Our findings indicate a gender influence on sleep disturbance prevalence, with females exhibiting a higher prevalence than males. These findings underscore the significance of sleep assessment and treatment in clinical or community environments.

BACKGROUND Eisenmenger syndrome develops from untreated or late-repaired cardiac shunts, causing irreversible pulmonary-vascular remodeling and systemic symptoms. Although timely repair has nearly eradicated Eisenmenger syndrome in high-income regions, delayed diagnosis in middle-income countries, especially when combined with chronic high-altitude hypobaric hypoxia, such as at approximately 2800 m (9186 ft) in the Ecuadorian Andes, can accelerate pulmonary hypertension through hypoxic vasoconstriction and erythrocytosis. We report a case of Eisenmenger syndrome 2 decades after surgical atrial septal defect closure. CASE REPORT A 46-year-old woman living at high altitude presented with severe cyanosis and heart failure 22 years after atrial septal defect closure. She had marked hypoxemia and secondary erythrocytosis. Echocardiography showed suprasystemic pulmonary artery pressure, severe right-chamber dilation, and reduced right ventricular systolic function. Right-heart catheterization confirmed Eisenmenger physiology with severe pulmonary-vascular resistance and low cardiac index. Chest computed tomography showed marked pulmonary artery enlargement without thromboembolic disease. Multidisciplinary management included bosentan 125 mg twice daily, tadalafil 10 mg once daily, nocturnal oxygen, diuretics, and anticoagulation, resulting in symptomatic stabilization and discharge on day 4. Transplant evaluation was initiated. CONCLUSIONS Delayed atrial septal defect repair at high altitude can lead to irreversible Eisenmenger syndrome, for which current therapy is palliative. Early defect recognition and closure, congenital heart screening, and access to pulmonary vasodilators and transplant programs are imperative in resource-constrained mountainous regions.

BACKGROUND: Dyslipidaemia remains a leading cause of death in Germany despite an improving therapeutic landscape, with many patients not achieving guideline-recommended low-density lipoprotein cholesterol (LDL-C) goals. Bempedoic acid, an adenosine triphosphate citrate lyase inhibitor, is a recent addition to the therapeutic landscape with proven efficacy in randomised controlled trials; however, its use varies between centres. We aimed to assess the short-term, real-world effectiveness of bempedoic acid in lowering LDL-C levels in patients in Germany. METHODS: This retrospective, observational study was conducted using data from patients with primary hypercholesterolaemia or mixed dyslipidaemia, collected before and approximately 3 months after initiating bempedoic acid in 7 specialised lipid outpatient clinics in Germany. RESULTS: Data were analysed from a total of 641 patients, with a mean age (standard deviation [SD]) of 63.2 (11.3) years. The addition of bempedoic acid significantly reduced LDL-C levels from a mean of 133.6 mg/dL at baseline to 101.8 mg/dL after 3 months (p < 0.001). The mean within-patient LDL-C reduction was 31.8 mg/dL and the mean patient-level percentage change was -17.5%. Mean patient-level changes were -4.9% for HDL-C and -12.0% for total cholesterol; triglycerides did not change significantly. At 3 months, patients not receiving any lipid-lowering therapy (LLT) other than bempedoic acid had a mean patient-level LDL-C reduction of 27.1%; corresponding mean reductions were 23.7% with ezetimibe, 20.3% with PCSK9 inhibitor therapy, 9.0% with statin therapy and 6.1% with statin plus ezetimibe. Suspected adverse events were documented in 218/641 patients (34.0%), and 171/641 (26.7%) had discontinued bempedoic acid by follow-up. Myalgia was the most commonly reported adverse event in patients discontinuing treatment (75 cases). CONCLUSIONS: Findings from this real-world, multicentre study conducted in Germany show that bempedoic acid may present an effective treatment option for patients with hypercholesterolaemia who are already receiving LLT, in addition to being an effective option for patients not receiving/tolerating other LLTs. The magnitude of LDL-C reduction differed across background treatment strategies, while suspected adverse events and treatment discontinuation were common in this specialist-care cohort.

BACKGROUND: A considerable proportion of patients experience post-acute sequelae of COVID-19 (PASC). Increasing evidence suggests sex-related differences, yet systematic longitudinal analyses remain limited. This study aimed to examine sex-specific differences in symptoms, psychological burden, work productivity and physical activity over ten months following acute COVID-19. METHODS: In this prospective, dynamically enrolled cohort study, patients with ongoing symptoms after confirmed SARS-CoV-2 infection were followed over a 10-month observation period. Patients conducted at the post-COVID outpatient clinic of the department of respiratory medicine and infectious diseases at Hannover Medical School, Germany. The assessment included patient-reported outcome measures, pulmonary function tests, six-minute walk tests, and capillary blood gas analysis. All outcome comparisons between sexes were adjusted for age, BMI, COVID-19 severity, and comorbidities using generalised linear mixed-effects models, with sex-by-time interaction terms tested to assess whether differences changed over follow-up, and p-values corrected for multiple testing across all outcome comparisons using the Holm method. A sensitivity analysis was performed in the subgroup of patients with complete follow-up at all four visits. RESULTS: Five hundred ninety patients attended to our clinic and a total of 433 patients were eligible and consecutively enrolled. Males were older (56 years vs. 52 years, p = 0.002), had more cardiovascular comorbidities (16% vs. 5%, p < 0.001), and experienced more severe COVID-19 (28% vs. 8%, p < 0.001). After adjustment for age, BMI, COVID-19 severity, and comorbidities, and Holm correction for multiple testing across all 27 outcome comparisons, females showed higher fatigue (Fatigue Assessment Scale, adjusted β = 3.3, Holm-adjusted p = 0.006), higher anxiety (GAD-2, β = 0.5, p = 0.021), lower quality of life (EQ-5D-3L, β = -0.6, p = 0.004), and greater work productivity impairment, both as a continuous score (WPAI-VAS, β = 1.3, p = 0.031) and as a binary indicator of clinically relevant impairment (OR = 3.0, p = 0.020). Females also had higher percent-predicted (pp) total lung capacity (p < 0.0001) and lower pCO (p < 0.0001), whereas males had higher pp diffusion capacity (p = 0.001). Headache (p < 0.001) and chest tightness (p = 0.011) were reported more frequently by females. None of these differences varied significantly over the 10-month follow-up (all sex-by-time interaction p ≥ 0.41), indicating no evidence that these differences changed over time. No significant sex differences remained after adjustment for depression (PHQ-2), lung function parameters, sex/height-adjusted exercise capacity, post-exercise dyspnoea or oxygen saturation, or most acute-COVID-19 symptoms other than headache and chest tightness. Regression models separately for each sex revealed fever (OR = 2.48, 95% CI: 1.11-5.57, p = 0.027) and diarrhoea (OR 2.33, 95%CI: 1.05-5.16, p = 0.038) during acute COVID-19 were associated with higher odds of work productivity impairment (WPAI-VAS ≥ 2) in males. In females, higher BMI (OR = 2.06, 95% CI: 1.13-3.76, p = 0.018) and dyspnoea during acute COVID-19 (OR = 4.38, 95% CI: 1.55-12.40, p = 0.005) were associated with increased odds. Formal interaction analyses showed a significant interaction only for dyspnoea after Holm correction. CONCLUSIONS: After accounting for baseline imbalance in age, BMI, COVID-19 severity, and comorbidities, and after correcting for multiple testing, sex-specific differences persisted for fatigue, anxiety, quality of life, and work productivity impairment, as well as selected lung function parameters. These differences did not change significantly across the 10-month observation period and did not show a significant sex-by-time interaction. The findings support the need for individualised, sex-specific follow-up focused on fatigue, psychological burden, and work productivity in patients with PASC.

BACKGROUND: Extreme weather events (EWEs) are becoming more frequent, but few have assessed the joint effects of floodings and power outages (POs) on health. OBJECTIVE: We aimed to quantify the independent and joint effects of flooding and POs on hospitalizations for cardiovascular diseases (CVDs). METHODS: Associations between flooding/POs and CVD hospitalizations in New York State (NYS) were estimated using distributed lag nonlinear models (DLNMs) within a quasi-Poisson regression framework, adjusting for PM weather factors and time-varying factors. We also evaluated length of stay, costs and comorbidities, thresholds, and compared the before and during COVID-19. Stratified analyses were conducted by CVD subtypes, demographics, season, and urbanicity. RESULTS: Flooding and POs were independently associated with total and specific CVDs, but the impact was stronger when they co-occurred (highest RR = 1.09, 95% CI: 1.03-1.15). CVD risk increased when flooding persisted for >3 days and when POs exceeded 15.3%. Flooding/POs were associated with longer hospital stays and higher comorbidities. Flooding/PO joint occurrence showed larger risk of CVD hospitalization during COVID-19, although not statistically significant. Stronger joint effects were observed on subtypes of hypertension, stroke, and ischemic heart disease, people over 65 years, those with Medicaid or no insurance coverage, rural residents, and during winter/spring. SIGNIFICANCE: This study highlights the health impacts of co-occurring environmental hazards of flooding and POs, revealing seasonal and temporal patterns and identifying vulnerable subgroups. Targeting susceptible population and deploying preparedness efforts in critical time windows may help mitigate related excess CVD burden. IMPACT: Our study provides new evidence on the impact of co-occurring flooding and POs on CVD hospitalizations. We found that their joint occurring is associated with greater increases in CVD hospitalizations than either exposure alone, disproportionately affecting older adults, socioeconomically vulnerable populations, and rural communities. Distinct seasonal, temporal, and threshold patterns were identified for flooding and POs. These findings offer useful information for emergency management agencies to reduce CVD burden during compound hazard events.

Psychocardiology connects the biological reality of cardiovacular diseases with the subjective experience of the patient. In cases of cardiac arrhythmias, this relationship is particularly evident: cardiac arrhythmias are measurable electrophysiological events but they are also subjectively perceived, emotionally evaluated and embedded in a patient's biography. The objective burden of arrhythmia does not always correlate with the degree of subjective suffering. Although modern electrophysiology provides highly differentiated diagnostic and interventional treatment options, the question of the individual experience of illness often remains secondary. This article discusses cardiac arrhythmias from a psychocardiological and psychosomatic perspective. It focuses on the heart-brain axis, the role of anxiety, depression, hypervigilance and illness perception as well as atrial fibrillation as a model of a biopsychosocial disorder. In addition, the heart is considered as a special organ where its activity can be directly perceived and is culturally associated with life, safety, identity and vulnerability. Psychocardiology is not understood as psychologizing cardiac disease but as an integrative clinical attitude that takes both biological findings and subjective experience seriously.

Platelets and neutrophils form dynamic platelet-neutrophil complexes (PNCs) that connect vascular injury with inflammatory effector responses. Glycoprotein VI (GPVI), a platelet-restricted immunoreceptor, converts collagen- and fibrin-related cues into ITAM signaling, granule secretion and integrin activation. GPVI is not known to function as a direct platelet-neutrophil adhesion receptor. Instead, GPVI-dependent platelet activation generates an adhesive and secretory platelet phenotype that favors PNC formation through P-selectin/PSGL-1, GPIbα/Mac-1, integrin-dependent bridging, and soluble mediators. Once formed, PNCs can enhance neutrophil recruitment and activation and, under permissive inflammatory conditions, may promote NET formation. Neutrophil extracellular traps (NETs) may then provide procoagulant scaffolds that amplify vascular inflammation and tissue injury. This review synthesizes the mechanistic steps linking GPVI signaling to PNC formation and NET release and evaluates evidence for this framework in acute lung injury and sepsis, sterile inflammation and autoimmune disease, cardiovascular thrombosis, and cancer-associated thrombosis and metastasis. Together, these findings suggest that GPVI sits upstream of platelet-neutrophil interactions and links platelet activation to neutrophil effector responses.