To evaluate the proof-of-concept feasibility of identifying individuals at high risk of cardiovascular disease through community-based PocDoc Healthy Heart point-of-care screening in a large, ethnically diverse, disadvantaged real-world cohort in the United Kingdom.

Proof-of-concept, non-randomised, non-interventional real-world cardiovascular disease risk case finding study in adults aged 18 years or older in real-world communities across the United Kingdom. Main outcome measures were identification of individuals with high risk of cardiovascular disease, defined as QRISK3 score ≥10%; and individuals meeting the criteria for weight loss, smoking cessation, or hypertension management services.

A total of 4,256 individuals (mean age 49 years, 57% male, 31% body mass index ≥30 kg/m2) were included in the Primary Cohort. The Targeted Outreach and Workplace sub-cohorts comprised 1,970 and 756 individuals, respectively. In the Primary Cohort, 35% (1,486/4,256) had high (>5.0 mmol/L) total serum cholesterol, 10% were smokers, 10% met criteria for weight loss services and 19% met criteria for hypertension management services. QRISK3 scores were generated for individuals who had not previously had a cardiovascular disease event (~90% of screened individuals). A QRISK3 score ≥10% was found in 20% (784/3,842) of individuals in the Primary Cohort, 26% (457/1,743) in the Targeted Outreach sub-cohort, and 6% (41/701) in the Workplace sub-cohort. In the Primary Cohort, 60% (472/784) of individuals with a QRISK3 score ≥10% were not being treated with a lipid-lowering therapy at the time of testing.

In this proof-of-concept study, community-based point-of-care screening identified individuals with elevated cardiovascular risk and unmet cardiovascular risk management needs. These findings are hypothesis-generating and provide the rationale for further controlled studies with systematic follow-up and health-economic analyses to evaluate whether this approach can deliver improved clinical and system-level outcomes.

ClinicalTrials.gov NCT06258005.

Choosing an appropriate imputation strategy for clinical datasets requires understanding which missing data mechanism is operative, yet most imputation benchmarks conflate performance across mechanisms. The present work addresses this gap by conducting the first mechanism-stratified comparison of three imputation approaches-CHIT, Multiple Imputation by Chained Equations via BayesianRidge (MICE), and Random-Forest-based Iterative Imputation-across Missing Completely at Random (MCAR), Missing at Random (MAR), and Missing Not at Random (MNAR) conditions. Three health datasets serve as experimental platforms: the Chronic Kidney Disease (CKD) dataset, the Heart Disease Dataset (HDD), and the Mice Protein Expression Dataset (MPED). Domain-knowledge-driven missingness patterns are constructed for each mechanism (Fig 2) at approximately 20-25% overall rates. Eight classifiers-KNN, Logistic Regression, SVC, Decision Tree, Random Forest, Gaussian Naïve Bayes, MLP, and a deep neural network-are trained on imputed data following GridSearchCV optimisation. Across all conditions, CHIT achieves near-perfect or perfect downstream classification, with SVC reaching up to 100% accuracy on the CKD dataset under MNAR, and 98.75% under MCAR and MAR. Competing methods degrade by up to 19.38 percentage points under MNAR, while CHIT's accuracy remains stable. Two structural properties account for this resilience: an iterative enrichment of the regression training set as records are completed, and a within-record prioritisation of the most data-scarce features for model-based filling. Taken together, these results provide mechanism-specific guidance for imputation selection in health informatics pipelines. Statistical significance of classifier accuracy differences between CHIT and MICE was assessed using McNemar's test (two-tailed, continuity-corrected chi-square) applied to the exact binary prediction vectors from each experiment [n_test = 80]. Ninety-five percent confidence intervals for all reported accuracy values were computed using the Wilson score method [z = 1.96]. The 42-configuration mean accuracy and standard deviation for CHIT are reported in Supplementary Table S1. Full McNemar results with confidence intervals are in Supplementary Table S2.

In Brazil, regional disparities in cardiovascular disease (CVD) mortality persist, with no population-based study having examined CVD mortality at the municipal level in the Central-West region. This study analysed the epidemiological profile, temporal trends, spatial distribution, and socioeconomic correlates of CVD mortality in Campo Grande, Mato Grosso do Sul, Brazil (2013-2022). A population-based ecological study used data from the Brazilian Mortality Information System. Five CVD groups were analysed: ischaemic heart disease (IHD), heart failure (HF), arrhythmias (ARR), cardiomyopathies (CMP), and inflammatory heart diseases (INF). Temporal trends were assessed using Poisson, Prais-Winsten, and Joinpoint regression. Spatial distribution was examined through Kernel Density Estimation and Local Indicators of Spatial Association (LISA). Socioeconomic correlates were assessed using Spearman's correlation with neighbourhood-level indicators. Of 59,392 registered deaths, 8,148 (13.7%) were CVD-related. IHD was the dominant cause (79.5%), with males accounting for 59.3% of deaths (IRR 1.59; 95% CI 1.46-1.74) and individuals aged ≥60 years representing 75.2%. Overall crude CVD mortality increased by 26.1% over the study period, with an estimated mean annual increase of 2.5% (APC + 2.5%/year; 95% CI 1.7-3.3; p < 0.001) and significant acceleration after 2019. A striking proportion of IHD deaths occurred outside hospital settings (67.3%), with home deaths alone surpassing hospital deaths (43.9% vs. 32.7%). Spatial analysis identified significant high-high mortality clusters in central-western neighbourhoods and low-low clusters in eastern neighbourhoods (13 and 5 neighbourhoods, respectively; Global Moran's I = 0.555, p < 0.001), with cluster patterns varying by disease group. Socioeconomic correlates showed a consistent pattern across most CVD groups, with higher mortality in more socioeconomically advantaged neighbourhoods, except for inflammatory heart disease, which showed the opposite pattern. This first municipal-level CVD mortality analysis in Central-West Brazil identified significant spatiotemporal heterogeneity and a high burden of out-of-hospital IHD deaths, providing actionable evidence for geographically targeted cardiovascular prevention strategies.

Atrial fibrillation (AF), highly prevalent in older individuals, is associated with frailty and disability. AF therapy is based on rhythm control (RhythmC) to restore sinus rhythm or rate control (RateC) to lower the heart rate. Published guidelines do not indicate a preference for one over the other for older people.

This study aims to evaluate whether RhythmC is more effective than RateC in hindering the progression of frailty and disability.

The Cardioversion of Atrial Fibrillation and Frailty in the Elderly (CAFFE) study is a prospective, multicenter, observational cohort study that includes 4 groups of patients: (1) adults age 75 years or older undergoing RhythmC treatment; (2) adults aged 65 to 74 years undergoing RhythmC treatment; (3) adults 65 years or older undergoing RateC treatment; and (4) adults 65 years or older without overt chronic conditions as the control group (n=40 in each group). At baseline, all participants will undergo a Comprehensive Geriatric Assessment (CGA) and analyses of inflammation and metabolomics. At home, a device will evaluate each participant's heart rhythm, activity profile, and sleep. After 1 month, the CGA will be repeated.

The CAFFE study was funded as a Research Project of National Interest by the Italian Ministry of University and Research (October 2023). Ethical committee final approval was given in June 2024. In October 2025, the coordinating center had enrolled 31 of 40 patients with AF (mean age 78, SD 9 years; 8 [25.8%] women; mean CHA₂DS₂-VA score 4.2, SD 1.2; 13 [43.3%] robust participants). All centers are now completing the enrollment (103/160 participants), and the analysis of inflammatory mediators has started. The results are expected to be published in summer 2027.

The CAFFE study will evaluate the effectiveness of AF management strategies in older patients. If RhythmC can slow the progression of frailty and disability, specific clinical trials should more definitively address this knowledge gap.

Stroke is a leading cause of long-term functional disability and often requires caregiver support during recovery. Informal caregivers of post-stroke patients face multiple challenges related to medical and nursing competence, workload, and access to information. These challenges remain insufficiently explored and inadequately addressed in healthcare systems. Using predefined criteria, we searched PubMed and Google Scholar for English-language studies involving human participants and published between January 2015 and August 2025 on issues related to informal caregiving. After initial abstract screening, we selected 60 relevant publications from each database for discussion in this narrative review, using a PRISMA-based approach. The findings reveal a multidimensional caregiving burden, with nearly 90% of caregivers reporting shortages in practical knowledge and skills training. They also often face psycho-emotional and economic strain, compounded by a lack of institutional support and social isolation. Caregivers experience chronic frustration and exhaustion, leading to depressive and somatic symptoms, while also lacking adequate medical attention. Their needs are largely unsupported and unmet by available institutional support. There is a lack of systemic solutions to integrate caregiving responsibilities with personal activities and preventive healthcare. These issues necessitate urgent research and the implementation of effective supportive interventions to enhance the quality of life of post-stroke caregivers. Key recommendations include developing standardized educational programs implemented at hospital discharge, ensuring access to professional medical support, and establishing flexible respite care services to prevent caregiver burnout. Caregivers' psychosocial and somatic wellbeing is essential for the successful rehabilitation and recovery of post-stroke patients.

Cardiovascular diseases (CVDs) remain one of the leading causes of morbidity and mortality worldwide, with cardiomyocyte death playing an important role in myocardial injury, pathological cardiac remodeling, and the progression of heart failure. Programmed cell death (PCD), including apoptosis, pyroptosis, ferroptosis, cuproptosis, and disulfidptosis, plays an essential role in maintaining cellular homeostasis; however, its aberrant activation or dysregulation can contribute to cardiovascular injury and disease progression. Increasing evidence indicates that these PCD pathways are not independent but form a complex regulatory network through shared mechanisms, including mitochondrial dysfunction, oxidative stress, inflammatory activation, and metabolic imbalance, thereby contributing collectively to the development and progression of CVDs. Therefore, targeting PCD-related pathways has emerged as a promising therapeutic strategy. Natural products and their bioactive constituents can exert cardioprotective effects by regulating PCD-related signaling networks through multiple targets and pathways, thereby alleviating cardiomyocyte death, oxidative stress, inflammation, and cardiac dysfunction. Representative bioactive compounds, including salvianolic acid B, resveratrol, quercetin, and astragaloside IV, have demonstrated potential to modulate PCD-related signaling pathways in experimental models of CVDs. This review summarizes the molecular mechanisms and pathological roles of apoptosis, pyroptosis, ferroptosis, cuproptosis, and disulfidptosis in CVDs, elucidates the regulatory crosstalk among different PCD pathways, and systematically reviews the research progress on the cardioprotective effects of natural products and their bioactive constituents through targeting PCD. In conclusion, natural products targeting dysregulated PCD pathways may represent a promising multi-target therapeutic strategy for cardiovascular protection; however, current evidence is derived predominantly from preclinical studies, and further in-depth mechanistic investigations and high-quality clinical studies are warranted to validate their therapeutic potential and clinical translational value.

Natural killer (NK) cells and monocytes are central components of the innate immune system, playing critical roles in host defense, immune surveillance, and inflammation. Functional alterations in these cell populations are implicated in cancer, infectious diseases, cardiovascular disease, and responses to environmental and psychosocial stressors. Accurate measurement of NK cell and monocyte distribution and function is therefore essential for both basic and translational immunology. In large-scale or longitudinal studies, cryopreserved peripheral blood mononuclear cells (PBMCs) are commonly used to enable standardized analyses across time and sites; however, cryopreservation and thawing can adversely affect cell viability and function. This chapter presents a reproducible protocol for the cryopreservation, thawing, and functional assessment of NK cells and monocytes from human PBMCs. PBMCs are cryopreserved using a 9:1 ratio of fetal bovine serum (FBS) and dimethyl sulfoxide (DMSO), allowing long-term storage at ultra-low temperatures while preserving cellular integrity. The thawing process utilizes a nuclease to minimize cell clumping, enhancing cell recovery and viability. Following thawing, PBMCs are prepared for downstream functional assays. NK cell function is assessed using a standard degranulation assay following coculture with K562 target cells, providing a robust measure of cytotoxic capacity. Together, this protocol offers a practical guide for the reliable measurement of NK cell and monocyte distribution and function from cryopreserved PBMCs, supporting high-quality immunological analyses in clinical and population-based research.

Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiac disorder, yet remains substantially underdiagnosed in clinical practice. Although current guidelines define HCM primarily based on left ventricular wall thickness, this approach alone does not capture the full spectrum of disease expression. Comprehensive phenotyping using multimodality imaging, combined with genetic testing and systematic family screening, allows for more accurate diagnosis and earlier detection, although its integration into routine clinical algorithms remains incomplete. Clinical outcomes and therapeutic strategies in HCM are largely driven by disease-related complications. These include heart failure, atrial fibrillation, ventricular arrhythmias, and sudden cardiac death, where risk stratification and prevention are central. While left ventricular outflow tract obstruction represents a major therapeutic target with rapidly evolving treatment options, alternative obstruction phenotypes and non-obstructive disease have received comparatively less attention. In these patients, symptoms are often determined by microvascular dysfunction, diastolic impairment, and myocardial fibrosis, contributing to myocardial ischemia and heart failure. Recent advances in targeted therapies, particularly cardiac myosin inhibitors, highlight the increasing importance of precise phenotypic characterization for treatment selection. However, their long-term impact on disease progression and clinical outcomes remains to be established. Overall, HCM should be considered a dynamic and heterogeneous disease continuum requiring individualized, phenotype-driven diagnostic and therapeutic strategies.

Refractory functional tricuspid regurgitation (TR) secondary to annular dilatation portends poor prognosis, although conventional open tricuspid surgery carries high-risk in elderly patients. The optimal K-Clip deployment geometry for maximal annular reduction remains undefined.

An 89-year-old pacemaker-dependent man with decompensated right heart failure and refractory functional TR was prohibitively high-risk for open surgery. Preoperative imaging identified anatomy less favorable for transcatheter edge-to-edge tricuspid repair. K-Clips were implanted perpendicularly to tricuspid commissures via the commissural symmetrical closure (CSC) strategy, yielding significant annular reduction. Three-month follow-up showed sustained TR improvement and stable clip positioning.

Perpendicular orientation geometrically maximizes annular plication, enabling optimal annular contraction and TR relief. Dual fluoroscopic and live 3D transesophageal echocardiographic guidance ensures safe and precise deployment.

The commissural symmetrical closure strategy optimizes K-Clip geometric alignment to maximize tricuspid annular reduction and ameliorate severe functional TR, offering a safe and feasible transcatheter annuloplasty approach for high-risk elderly patients.

Individuals with severe mental illness have an elevated risk of developing cardiovascular diseases. This study aimed to examine adherence to an evidence-based model for physical healthcare by using the Physical Health Care Fidelity Scale and to explore whether adherence is associated with risk factors in patients.

This multicenter study was conducted at clinical sites within specialist mental health services in Norway. Data were collected from 230 patients aged 16 years or older with schizophrenia or bipolar spectrum disorders, or those currently using antipsychotic medications. Using generalized linear mixed models, we explored the relationship between fidelity scores and cardiometabolic risk factors (daily smoking, hypertension, obesity, sedentary behavior, diabetes, lipid disorder, and unhealthy diet).

The sites generally demonstrated poor fidelity scores, reflecting a low level of specialist health care implementation of evidence-based practices. All assessed risk factors were highly prevalent, with daily smoking and/or snuff use being the most common (58.1%). Higher fidelity scores were assessed on the Policies subscale than on the Practices subscale, indicating that evidence-based knowledge regarding the identification and treatment of cardiovascular risk factors was more integrated into established policies and procedures than into the actual implementation of the interventions reaching patients. Associations between fidelity and patient clinical outcomes were non-significant after adjustment.

Specialist healthcare providers demonstrated low adherence to evidence-based practices for cardiovascular risk management. Standardized fidelity measures can pinpoint areas for targeted improvement, and future studies should explore how fidelity levels relate to clinical outcomes.

ClinicalTrials.gov Identifier: NCT03271242 (Registration date: 05.09.2017).