Waterpipe (WTP) tobacco smoking is highly prevalent in Vietnam. WTP use is associated with higher nicotine exposure and increased risk of pulmonary and cardiovascular diseases. The aim of this study is to understand WTP use and how it may influence smoking behaviors and cessation.

We conducted a secondary analysis of data from the mHealth Messaging to Motivate Quitline Use and Quitting (M2Q2) randomized trial, which evaluated a mobile health peer-texting intervention in Northern Vietnam. Logistic and mixed-effects logistic regression was used to assess the association between WTP, CO-verified cessation, and Quitline use, after accounting for commune-level clustering and adjusting for demographic factors and randomization.

Among 749 male smokers (mean age: 42.7 years), 53% reported WTP use. Higher education (high school: adjusted odds ratio, AOR=0.61; CI: 0.43-0.86, college: AOR=0.47; CI: 0.30 - 0.73), and age >60 years (AOR=0.53; CI: 0.28-0.99) were inversely associated with WTP use, compared to smokers who only completed secondary school, and were aged <30 years, respectively. Compared to non-WTP users, WTP users smoked fewer cigarettes daily (p<0.001), smoked sooner after waking (p<0.001), spent more money weekly on tobacco products (p<0.001), and began smoking at an earlier age (p=0.02). WTP was not significantly associated with CO-verified cessation, and users had lower non-significant Quitline use.

WTP users differed from non-WTP users in demographic and smoking behaviors. WTP did not significantly affect CO-verified cessation, with a non-significant trend of reduced Quitline use, suggesting barriers to treatment uptake. Tailored cessation strategies that address WTP-specific challenges are needed to improve outcomes in this high-risk group.

To quantify the association between cardiovascular autonomic neuropathy (CAN) and heart failure (HF) in individuals with type 2 diabetes (T2D).

Two hundred T2D individuals were recruited from two Danish outpatient clinics between 2021-2024. CAN was defined by abnormal cardiovascular autonomic reflex test results. HF outcomes included the primary outcome of elevated N-terminal pro-brain natriuretic peptide (NT-proBNP) levels > 125 pg/mL, WATCH-DM risk score. Symptomatic HF was defined by New York Heart Association (NYHA) classification score ≥II. We assessed the association between measures of CAN and HF using logistic and linear regressions, adjusting for confounders and testing for effect modification between CAN, NYHA, and WATCH-DM risk scores.

Among 176 individuals with NT-proBNP assessments, the median (interquartile range [IQR]) age was 63 (IQR: 55, 70) years, 61% were men, and median diabetes duration was 17 years (IQR: 11, 24). Among 134 individuals with valid CAN assessment, 40% had CAN and 52% of those had elevated NT-proBNP compared to 23% of individuals without CAN. In the fully adjusted model, CAN was associated with 6.2 times higher odds (95% CI: 2.1; 20.8) of elevated NT-proBNP levels compared to individuals without CAN. The association remained statistically significant in asymptomatic individuals, and in individuals with a low-to-moderate WATCH-DM risk score.

CAN is associated with elevated NT-proBNP levels in individuals asymptomatic for HF. This suggests that CAN may complement established biomarkers to identify individuals with earlier HF stages, for timelier treatment initiation.

Preeclampsia (PE) is a severe hypertension-related complication of pregnancy, driven by crosstalk between environmental exposures and genetic susceptibility. Cold exposure is recognized as a risk factor for PE, yet its underlying molecular mechanisms remain unclear. This study aimed to determine whether cold stress exacerbates PE-like phenotypes and clarify the pathogenic function of placental Map7.

Pregnant mice were subjected to an L-NAME-induced PE-like model with or without chronic cold exposure. Maternal phenotypes, placental pathology, inflammation, and angiogenic balance were evaluated. Proteomics and immunofluorescence were used to identify and localize placental candidate proteins. In vitro macrophage manipulation and conditioned medium assays evaluated Map7's effects on macrophage polarization and trophoblast function.

Cold exposure markedly worsened PE-like manifestations, including hypertension, proteinuria, fetal growth restriction, and placental injury. Proteomics identified Map7 as progressively upregulated from controls to PE-like mice, and further in cold-exposed PE-like mice, prominently localizing in placental macrophages. MAP7 overexpression promoted M1-like macrophage polarization and inflammatory cytokine production via activating the NF-κB signaling pathway, whereas MAP7 knockdown attenuated these effects. Furthermore, conditioned medium from Map7-overexpressing macrophages impaired trophoblast proliferation, migration, invasion, and angiogenesis, which was reversed by MAP7 silencing.

Map7 mediates the cold stress-aggravated PE-like phenotype. Targeting the macrophage-associated Map7/NF-κB axis represents a potential therapeutic strategy for environmentally triggered placental immune dysfunction.

With global warming, extreme summer heat has led to a higher morbidity and mortality of heat stroke (HS). Although heat stress has been linked to arrhythmias and cardiomyocyte injury, the specific molecular mechanisms and effective intervention strategies remain to be clarified.

We retrospectively collected clinical data from HS patients. A rat HS model was established, and the underlying mechanisms were investigated using biochemical and electrophysiological approaches, combined with proteomics and metabolomics analyses of myocardial tissues and cells. In vivo and in vitro intervention experiments were performed using the mitochondrial reactive oxygen species (ROS) scavenger MitoTEMPO and calcineurin inhibitor (FK506).

Heat stress caused severe myocardial injury and electrocardiographic abnormalities in HS patients. HS rats exhibited increased susceptibility to ventricular arrhythmias (VAs), manifested by prolonged action potential duration (APD), increased Ca²⁺ transient duration (CaTD) and Ca²⁺ alternans ratio, and slowed conduction velocity (CV), which were linked to disrupted Ca²⁺ handling. Proteomics and metabolomics revealed that mitochondrial dysfunction was closely associated with heat stress-induced myocardial injury. Mechanistically, HS triggers intracellular Ca²⁺ overload, activating calcineurin. Calcineurin dephosphorylates DRP1 at Ser637 site and promotes its mitochondrial translocation, leading to DRP1-mediated mitochondrial fission and dysfunction, excessive mitochondrial ROS generation, and cardiomyocyte apoptosis. In addition, MitoTEMPO and FK506 treatment partially reversed HS-induced myocardial injury and VAs susceptibility by scavenging mitochondrial ROS and restoring mitochondrial function.

Heat stress triggers mitochondrial dysfunction through a Ca²⁺/ calcineurin/ p-DRP1(Ser637) axis, resulting in myocardial injury and VAs. The mitochondria-targeted antioxidant MitoTEMPO and FK506 partially alleviate these adverse effects by scavenging mitochondrial ROS and restoring mitochondrial function.

Cardiovascular diseases (CVDs) remain the leading cause of mortality worldwide, creating an urgent need for accurate, trustworthy, and clinically deployable artificial intelligence (AI) systems capable of supporting complex diagnostic decision-making. Although AI has advanced considerably in cardiovascular diagnosis, existing evidence remains fragmented across algorithms, data modalities, and isolated application domains, limiting a comprehensive understanding of clinically integrated AI systems. This study presents a PRISMA 2020-guided systematic review and proposes a clinically grounded six-layer taxonomy that organizes cardiovascular AI according to diagnostic objectives, data modalities, modeling paradigms, data integration complexity, interpretability and trustworthiness, and deployment maturity. A systematic search of PubMed, Scopus, Web of Science, IEEE Xplore, and ScienceDirect identified 226 records, of which 76 primary empirical studies met the predefined eligibility criteria and were included in the comparative evidence synthesis. The review demonstrates the evolution of cardiovascular AI from conventional machine learning applied to structured clinical data toward deep learning for physiological signals and medical imaging, followed by multimodal AI systems integrating heterogeneous clinical information. Comparative synthesis across the proposed taxonomy highlights substantial progress in predictive performance while revealing persistent challenges related to external validation, dataset representativeness, workflow integration, explainability, privacy, governance, and prospective clinical deployment. The review further distinguishes clinically validated technologies from emerging paradigms, including federated learning, foundation models, and agentic AI. Overall, the proposed taxonomy provides a unified framework for organizing contemporary cardiovascular AI research and offers a practical roadmap for evaluating the maturity, trustworthiness, and clinical readiness of next-generation intelligent diagnostic systems.

In dilated (DCM) and arrhythmogenic cardiomyopathies (ACM), monogenic variants in causative genes are key prognostic factors. In the general population, the clinical role of these variants remains debated.

This study aimed to determine the association between rare, predicted deleterious variants (PDrV) in DCM- and ACM-associated genes and disease-related outcomes in the general population.

Using United Kingdom Biobank whole-exome sequencing data, we identified PDrVs in 25 DCM/ACM-validated genes. We assessed disease penetrance in carriers and their risk for two primary outcomes-sudden cardiac death/malignant ventricular arrhythmias (SCD/MVA) and heart failure death/heart transplant (HF/HT)-using cause-specific Cox models accounting for competing risks.

Among 469,671 participants, 54.2% were females and the median age at baseline was 53.5 (IQR: 10.3). During a median follow-up of 14 years (IQR: 2), 5786 SCD/MVA and 4611 HF/HT events occurred. A PDrV was found in 12,973 (2.8%) individuals. Despite low penetrance for DCM (1.0%), PDrV impacted on both outcomes. Compared to noncarriers, PDrV carriers had a higher risk of SCD/MVA (HR: 1.28; 95% CI: 1.11-1.48). In participants free from DCM or other heart diseases at recruitment, SCD/MVA risk was solely associated with ACM genes (HR: 1.34; 95% CI: 1.07-1.69). Carriers also exhibited a higher risk of HF/HT (HR: 1.32; 95% CI: 1.08-1.62), which was not confirmed in subgroup without other heart diseases.

PDrV carriers have a higher risk of severe cardiac events, even without a clinical overt disease phenotype at baseline evaluation. Moreover, PDrV in arrhythmic genes significantly influence SCD/MVA risk, regardless of phenotypic diagnosis of DCM.

Long-term exposure to high-intensity endurance exercise induces significant physiological cardiovascular remodelling. However, recent evidence suggests that prolonged exercise in athletes, particularly those exposed to decades of intensive training, may be associated with features of cardiovascular "wear and tear". These include electrical changes such as an increased risk of sinus node dysfunction and atrial fibrillation as well as structural abnormalities such as focal non-ischemic fibrosis and coronary artery calcification, more frequently observed in middle-aged and older endurance athletes. These observations support that long-term high-intensity exercise may have deleterious cardiovascular effects in susceptible individuals, although the available data are primarily derived from male Caucasian athletes. While the clinical significance of these potentially maladaptive changes at the individual level remains uncertain, at a population level high intensities and volumes of physical activity are consistently associated with reduced cardiovascular and all-cause mortality compared with sedentary behaviour, although the incremental survival benefit may plateau at very high exercise volumes. This review critically appraises the available evidence on chronic adverse cardiovascular adaptations associated with intense endurance exercise, highlighting unresolved controversies, sex- and ethnicity-related knowledge gaps, and the need to balance potential risks against the well-established survival benefits of lifelong physical activity.

This report describes the design and baseline characteristics of the SPIRIT-HF trial and compares them with prior heart failure with mildly reduced or preserved ejection fraction (HFpEF/HFmrEF) trials.

In this multicenter, double-blind, placebo-controlled phase III trial, 730 patients aged ≥50 years with left ventricular ejection fraction (LVEF) ≥40%, New York Heart Association (NYHA) class II-IV symptoms, and either elevated N-terminal-pro-B-type natriuretic peptide (NT-proBNP) or HF hospitalization within 12 months were randomized 1:1 to spironolactone or placebo. The primary endpoint is a composite of rate of total (first and recurrent) HF hospitalizations and cardiovascular death within 24 months from randomization, which will be analyzed using the LWYY model. Secondary endpoints in a hierarchical order include total HF hospitalizations, CV hospitalizations, all hospitalizations, and cardiovascular death within 24 months from randomization. Results will first be analyzed based on the SPIRIT-HF dataset only. Then, a pre-specified individual participant data meta-analysis combining SPIRIT-HF and TOPCAT Americas will be conducted to refine treatment effect estimates. The median age of the patients enrolled in the SPIRIT-HF was 77.8 years, and 52% were women. The median LVEF was 55% (50-60), with 18% of patients having a LVEF between 40-49%. In SPIRIT-HF, prior HF hospitalization was similarly frequent (46.4% vs. 55%), but NT-proBNP was slightly higher (970 vs. 900 pg/ml) compared to TOPCAT Americas. However, the proportion of patients with NYHA class III (33% vs. 35%), patients with comorbidities such as atrial fibrillation at baseline electrocardiogram (25% vs. 25%) and chronic kidney disease (50% vs. 48%); and background therapy, such as beta-blockers (76% vs. 79%), and diuretics (83% vs. 89%), including loop diuretics (69% vs. 78%), were similar between SPIRIT-HF and TOPCAT Americas. Compared with prior HFpEF/HFmrEF trials, SPIRIT-HF patients demonstrated a higher risk with a similar proportion of patients with recent HF hospitalization (46.4%) and slightly higher NT-proBNP concentrations (970 pg/ml) at baseline.

SPIRIT-HF addresses key evidence gaps for spironolactone in high-risk HFpEF/HFmrEF, and could inform guideline recommendations on MRA use in this cohort.

This analysis of insurer-complete administrative data and claims from a United States database (Komodo Health) assessed the risk of serious infections, myocardial infarction (MI), stroke, and venous thromboembolism (VTE) among patients with ulcerative colitis (UC) initiating tofacitinib or biologic treatments.

Patients with UC initiating treatment with tofacitinib, ustekinumab, vedolizumab, or tumor necrosis factor inhibitors (TNFis) from May 31, 2018, to September 30, 2022, were included. Stabilized inverse probability treatment weights (sIPTWs) were calculated and Cox proportional hazards models with sIPTWs were used to calculate hazard ratios; bootstrapping was used to calculate 95% CIs.

In total, 5171, 10 424, 17 129, and 29 872 patients initiated tofacitinib, ustekinumab, vedolizumab, and TNFis, respectively. The mean patient age at index was 43.1 years and the mean follow-up was 359.2 days. At baseline, a greater proportion of patients initiating tofacitinib vs biologics had used ≥ 2 prior biologics (46.3% vs 7.5%-33.7%, respectively). Incidence rates (IRs)/100 patient-years (PY) of serious infections were 2.62, 2.73, 2.45, and 3.25 for tofacitinib, ustekinumab, vedolizumab, and TNFi, respectively. For MI/stroke and VTE the IRs/100 PY were, respectively, 0.13 and 0.17 for tofacitinib, 0.17 and 0.16 for ustekinumab, 0.17 and 0.23 for vedolizumab, and 0.19 and 0.33 for TNFi. There were no significant differences in the risk of developing serious infections, MI/stroke, or VTE between treatments.

No significant risk differences were observed among patients with UC initiating tofacitinib compared with biologics in a large US claims database. These findings add to evaluations of treatment risks vs benefits in patients with UC.

EUPAS103443.

Precision cardiac rehabilitation represents a pivotal approach in the secondary prevention of cardiovascular diseases, yet conventional assessment and intervention models are limited by their static and homogeneous nature. Blood metabolomics, through comprehensive analysis of endogenous small-molecule metabolites, provides a panoramic view of an individual's metabolic status and its dynamic evolution, offering a revolutionary tool for truly personalized and dynamic rehabilitation management. This review introduces the innovative concept of a "dynamic navigation" paradigm, systematically summarizing the application of blood metabolomics in constructing individualized metabolic fingerprints, achieving precise risk stratification, dynamically evaluating rehabilitation responses, and optimizing intervention strategies in real time. We explore the paradigm shift from static biomarkers to dynamic metabolic navigation, addressing the necessary technological integrations and clinical translation challenges inherent in this transition. Furthermore, we discuss future directions toward developing data-driven closed-loop rehabilitation systems that leverage continuous metabolic monitoring to enhance therapeutic efficacy. By bridging metabolomic insights with clinical practice, this dynamic navigation framework promises to transform precision cardiac rehabilitation and improve patient outcomes.