Background/Objectives: Self-management intervention strategies are recommended to address the needs of breast cancer survivors (BCSs) who have cardiovascular diseases (CVDs). Despite the benefits, these strategies are often suboptimally implemented, resulting in inadequate cardiovascular management among BCS with CVDs. The project aims to develop a nurse-led and GP-supported self-management (NGPS) intervention to reduce cardiovascular risks in BCS with CVDs and evaluate its feasibility and potential effects in primary care settings using the double diamond co-design process and the Medical Research Council (MRC) Framework for Developing and Evaluating Complex Interventions. Methods: The study will be conducted in two phases. In phase I, an evidence-based and co-designed NGPS protocol with end-users will be preliminarily developed based on the identified research evidence, relevant theories, practice guidelines and the current practice standards in Australia. The co-design workshop(s) will involve healthcare professionals and BCSs with CVDs to further refine and validate the developed preliminary protocol. In phase II, a one-group pre-post pilot study will evaluate the feasibility of the intervention and study procedures, such as recruitment, retention, adherence, acceptability, and safety as primary outcomes. The study will also preliminarily explore the effectiveness of the intervention such as physiological measures as secondary outcomes to inform a future large-scale trial. Phase II also involves follow-up qualitative interviews to explore participants' experiences of the pre-post pilot study. The participants will be recruited from primary medical centres in Victoria. Conclusions: The findings will provide a co-designed evidence-based intervention for primary care nurses and General Practitioners (GPs) to promote long-term health outcomes for patients with both breast cancer (BC) and CVDs. Clinical registration: ClinicalTrial.gov (registration No. NCTO7313397).

Pulmonary arterial hypertension (PAH) is a progressive disease leading to right ventricular (RV) hypertrophy and failure. This study aims to evaluate the prognostic value of combining the tricuspid annular plane systolic excursion/systolic pulmonary artery pressure (TAPSE/sPAP) ratio with right ventricular myocardial work (RVMW) parameters in patients with PAH, to improve early risk stratification.

A total of 43 PAH patients diagnosed via right heart catheterization were enrolled. Echocardiography-derived TAPSE/sPAP ratio and RVMW parameters, including right ventricular global work efficiency (RVGWE), global work index (RVGWI), global constructive work (RVGCW), and global wasted work (RVGWW), were measured. Clinical worsening events were recorded during a median 515-day follow-up. Statistical analyses included correlation tests, Firth penalized logistic regression, receiver operating characteristic (ROC) curves, and Kaplan-Meier survival analysis.

The TAPSE/sPAP ratio correlated negatively with RVGCW (r = -0.346, p = 0.023) and RVGWW (r = -0.417, p = 0.005), but not with RVGWE or RVGWI. Clinical worsening events occurred in 25.6% of patients, with significantly lower TAPSE/sPAP ratio (0.16 vs. 0.24 mm/mmHg), RVGWE (72.0% vs. 88.5%), and RVGWI (431.0 vs. 641.0 mmHg%) in the Event group (all p < 0.05). Multivariate Firth penalized logistic regression was used for combining TAPSE/sPAP ratio with RVGWE. ROC analysis demonstrated that the combination of TAPSE/sPAP and RVGWE yielded superior predictive power (AUC = 0.949, p < 0.001) compared to individual parameters.

Non-invasive assessment of TAPSE/sPAP ratio and RVGWE provides significant prognostic value in PAH. Their combination enhances early risk prediction, offering a practical tool for clinical management.

Background: Lipoprotein(a) [Lp(a)] is a genetically determined, atherogenic, and prothrombotic lipoprotein. However, its prognostic value in patients who undergo successful chronic total occlusion (CTO) percutaneous coronary intervention (PCI) remains undefined. Methods: This single-center retrospective cohort study included 1509 patients who underwent successful CTO PCI. The primary outcome was cardiovascular death; secondary outcome was major adverse cardiovascular events (MACEs, cardiovascular death or nonfatal myocardial infarction). Multivariable Cox regression and restricted cubic splines (RCS) assessed the association between Lp(a) and outcomes. Results: Over median follow-up of 810 days, 53 (3.5%) cardiovascular deaths and 62 (4.1%) MACEs occurred. Each 1-SD increase in log-transformed Lp(a) was associated with a 51% higher risk of cardiovascular death (aHR 1.51, 95% CI 1.11-2.05, p = 0.008) and a 44% higher risk of MACEs (aHR 1.44, 95% CI 1.09-1.91, p = 0.011). Compared with Lp(a) < 30 mg/dL, Lp(a) ≥ 50 mg/dL conferred a 2.07-fold higher risk of cardiovascular death (95% CI 1.07-4.00, p = 0.029) and a 1.94-fold higher risk of MACEs (95% CI 1.07-3.53, p = 0.030). RCS analysis demonstrated a linear dose-response relationship between log-transformed Lp(a) and both cardiovascular death (p for nonlinearity = 0.653) and MACEs (p for nonlinearity = 0.562). The association was modified by age, hypertension, and left ventricular ejection fraction and remained robust in sensitivity analyses. Conclusions: In patients undergoing successful CTO PCI, elevated Lp(a) was independently and linearly associated with higher risks of cardiovascular death and MACEs. These findings suggest that Lp(a) may serve as a useful prognostic marker to enhance risk stratification in this high-risk population. Large-scale prospective cohorts are needed to validate these findings before clinical translation can be considered.

Chronic right heart failure (RHF) is a complex, progressive syndrome that remains underrecognized and inadequately defined in current clinical guidelines, where it is often relegated to a secondary complication of left-sided heart disease. Because the thin-walled right ventricle (RV) is well adapted to maintain pressures within the highly distensible venous system well below plasma oncotic pressure but poorly equipped to sustain pressure overload, when myocardial failure supervenes, conventional RV systolic indices frequently fail to capture the very essence of the syndrome. This review clarifies the distinct pathophysiological and haemodynamic foundations of chronic RHF, framing it fundamentally as the heart's inability to decongest the systemic venous circulation. We highlight how backward failure, rather than isolated RV systolic dysfunction, drives systemic and multi-organ congestion. To bridge existing diagnostic gaps, we propose a pragmatic, diagnostic algorithm. Under this framework, a Definite Diagnosis of chronic RHF requires evidence of elevated right atrial/central venous pressures-defined as clinically raised jugular venous pressure plus an echocardiographic dilated inferior vena cava (>21 mm with <50% collapse)-alongside at least one of four minor criteria: (1) systemic or visceral congestion (e.g., persistent oedema, congestive hepatomegaly); (2) echocardiographic RV systolic dysfunction (TAPSE < 17 mm, FAC < 35%, S' < 9.5 m/s; RV free-wall strain > -20%); (3) non-invasive signs of pulmonary hypertension (TRV > 2.8 m/s); or (4) impaired RV-pulmonary arterial coupling (TAPSE/PASP ratio < 0.35). By centering diagnosis on systemic venous hypertension as a result of right heart backward failure rather than isolated RV metrics, this framework offers a coherent, readily applicable tool for diagnosing chronic RHF in routine clinical practice.

Acute aortic syndrome (AAS) comprises acute aortic dissection, intramural haematoma, penetrating atherosclerotic ulcer, and limited intimal tear, conditions that require rapid recognition because mortality and resource use are strongly influenced by time to diagnosis, anatomical extent, malperfusion, and the need for emergency surgical or endovascular intervention. This revised narrative review synthesizes contemporary evidence on clinical, genetic, environmental, and health-system determinants of prolonged hospitalisation, intensive care unit (ICU) utilisation, bed occupancy, and costs in patients with AAS. Beyond summarising established risk factors, the review adds a resource-oriented framework that links hypertension, advanced age, female sex, smoking-related comorbidity, hereditary aortopathies, haemodynamic instability, malperfusion, delayed diagnosis, operative complexity, and postoperative complications to measurable downstream outcomes such as ICU length of stay, total hospital length of stay, reoperation, readmission, and longitudinal imaging surveillance. We searched PubMed/MEDLINE, Scopus, Web of Science, and Google Scholar for relevant studies, registries, guideline documents, and cost analyses published between January 2000 and May 2026, with particular emphasis on studies from the last five years. The review was not designed as a meta-analysis; therefore, effect estimates are interpreted according to study design and generalisability. AAS imposes a disproportionate burden on hospital systems because high-risk patients often require advanced imaging, prolonged haemodynamic monitoring, complex open or endovascular repair, ICU care, and lifelong follow-up. Earlier diagnosis, structured risk stratification, targeted genetic evaluation, aggressive control of modifiable risk factors, and system-level pathways such as dedicated aortic networks may shorten hospital stay and reduce avoidable costs.

Background/Objectives: As population aging increases the prevalence of atrial fibrillation (AF), the use of direct oral anticoagulants (DOACs) has expanded for thromboembolism prevention. Although DOACs offer advantages over vitamin K antagonists (VKAs), gastrointestinal bleeding (GIB) remains the most common extracranial adverse event. Current guidelines address global bleeding risk but provide limited guidance on site-specific gastrointestinal risk assessment and prevention. This narrative review aims to summarize current evidence on the mechanisms, etiologies, and risk factors for DOAC-associated gastrointestinal bleeding and to propose a pragmatic, risk-based framework to support clinicians in individualized bleeding prevention. Methods: A narrative review of studies published between 2004 and 2025 was conducted, including randomized clinical trials, real-world evidence, meta-analyses, and major society guidelines. Evidence addressing DOAC safety profiles, gastrointestinal bleeding etiologies, patient-level risk factors, medication interactions, and preventive strategies was analyzed. Results: Gastrointestinal bleeding in patients treated with DOAC is strongly influenced by underlying gastrointestinal pathology, comorbid conditions, and concomitant medications. Established risk factors include prior gastrointestinal hemorrhage, Helicobacter pylori infection, gastrointestinal malignancy, diverticulosis, and angiodysplasia, as well as the use of nonsteroidal anti-inflammatory drugs (NSAIDs), antiplatelet therapy, or selective serotonin reuptake inhibitors (SSRIs). DOACs differ in gastrointestinal safety: apixaban consistently demonstrates the most favorable profile, whereas rivaroxaban and high-dose dabigatran show higher GIB rates. Preventive strategies such as H. pylori testing and eradication, proton pump inhibitor use in high-risk individuals, avoidance of NSAIDs and unnecessary antiplatelet therapy, and individualized DOAC selection may help reduce bleeding risk. Conclusions: Gastrointestinal bleeding risk in patients receiving DOAC therapy should be assessed using a site-specific and dynamic approach. A structured strategy integrating baseline risk evaluation, correction of modifiable factors, tailored anticoagulant selection, and risk-adapted follow-up may improve the safety of anticoagulation. The proposed framework may provide a pragmatic approach to individualized bleeding risk mitigation while preserving the benefits of DOAC therapy; however, prospective validation is required before its routine implementation can be recommended.

Transcatheter Edge-to-Edge Repair (TEER) is a therapeutic option established for older patients with heart failure and concomitant mitral regurgitation. Frailty is associated with prognosis after transcatheter valve interventions. However, despite clinical potential, evidence for gait speed as a simplified prognostic marker in patients undergoing TEER remains insufficient.

This study aimed to investigate the association between preoperative gait speed and mid- to long-term mortality after TEER.

We conducted a single-center retrospective cohort study of 97 patients (mean age: 78.9 ± 8.7 years; 56.7% male) who survived the first 7 days after TEER and had available preoperative gait speed data. Preoperative gait speed was assessed, and clinical data were obtained from medical records. Cox regression analysis was performed to elucidate the association between preoperative gait speed and mortality.

In Cox proportional hazards models, higher gait speed (per 0.1 m/s increase) was associated with lower mortality after adjustment for the Society of Thoracic Surgeons risk score and handgrip strength (hazard ratio: 0.81; 95% confidence interval: 0.68-0.97; p = 0.02). In time-dependent receiver operating characteristic curve analysis, gait speed showed moderate discriminative ability for mortality, with area under the curve values of 0.749 at 1 year and 0.710 at 2 years. A gait speed of 0.8 m/s was used as an exploratory threshold for survival stratification, and patients with gait speed < 0.8 m/s had lower survival than those with gait speed ≥ 0.8 m/s (log-rank p < 0.01).

Lower preoperative gait speed was associated with higher mid- to long-term mortality after TEER. Preoperative gait speed may provide clinically useful information for exploratory risk stratification, although the cutoff-based findings require external validation.

Background: Traditional cardiovascular risk models often overlook "residual risk" driven by psychopathological factors. This study investigates the exploratory prognostic baseline associations of Type D personality (TDP) and specific symptomatic dimensions with long-term all-cause mortality in patients with coronary artery disease (CAD). Methods: We conducted a retrospective case study based on hospital records evaluating 221 patients with confirmed CAD. Anatomical complexity was quantified via the SYNTAX Score (SS). Psychological profiling utilized the DS14 scale for TDP and the SCL-90 for granular symptoms (depression, anxiety, and hostility). Mortality was analyzed over a mean follow-up of 1026 days using multivariate Cox proportional hazards models. Results: Over a mean follow-up of 1026 days, the overall all-cause mortality rate was 33.0% (n=73). TDP prevalence was 19.0% (n=42) and significantly correlated with higher anatomical complexity (SS: 26.21 vs. 15.49; p<0.001). In the adjusted psychological model, baseline anxiety symptom severity presented an exploratory, borderline relationship with survival (HR = 0.941; p=0.049), with the 95% confidence interval upper bound reaching the null threshold (1.000), suggesting a potential, hypothesis-generating "Anxiety Paradox". The psychological model demonstrated variations in descriptive validation indices (C-index = 0.624) compared to a baseline model integrating trait metrics and anatomical severity (C-index = 0.527). Significant correlations were confirmed between SS and psychological distress (r=0.493). Conclusions: TDP components and granular psychological tracks show significant baseline associations with coronary anatomical distributions, while anxiety dimensions present an exploratory relationship with long-term survival. Given the lack of adjustment for major clinical determinants of mortality (such as age, comorbidities, or ventricular function), these findings must be interpreted strictly as hypothesis-generating and exploratory.

Background: Cardiovascular (CV) risk estimation is usually based on the assessment of classic risk factors and the extent of coronary artery stenosis. However, a substantial rate of acute coronary syndromes (ACS) and sudden cardiac deaths (SCD) is observed in patients with high-risk atherosclerotic plaques (HRP), even in the absence of significant stenosis. Therefore, this study aimed to evaluate the predictive value of traditional clinical risk factors for the presence of HRP in patients scheduled for coronary computed tomography (CCT). Methods: This single-center study included 123 patients undergoing CCT for suspected coronary artery disease (CAD). Atherosclerotic plaque morphology (HRP) and the degree of coronary artery stenosis (CAD-RADS categories) were assessed in all the patients. CV risk factors, including LDL serum levels and CT Calcium score (CS), were analyzed. Results: The study cohort was mostly males (54.5%), with an average age of 60.40 ± 12.45 years and typical risk factors: hypertension (70%), diabetes (22%), obesity (30%), and smoking (20%). Most patients (88%) were found to have coronary atherosclerosis with nonobstructive disease (CAD-RADS 1-2) in 39% of patients. HRP was confirmed in over one-fifth of the participants (22%), with half of the patients in the CAD-RADS 2 category. There were no differences in CV risk factors between patients with and without HRP in CCT. No significant clinical predictor of HRP in CCT was identified. Conclusions: CV risk factors do not predict HRP in CCT, which may underestimate the real risk of ACS and SCD.

Peroxisome proliferator-activated receptors (PPARα, PPARβ/δ, and PPARγ) are ligand-activated nuclear transcription factors that orchestrate key metabolic and immuno-inflammatory networks governing hepatic homeostasis. By regulating fatty acid oxidation, insulin signaling, bile acid metabolism, and hepatic stellate cell activation, PPARs integrate metabolic and inflammatory cues central to the pathogenesis of chronic liver disorders. Chronic liver diseases (CLDs) constitute a major and growing global health burden. Metabolic dysfunction-associated steatotic liver disease (MASLD), now affecting up to one-third of the adult population worldwide, is closely linked to type 2 diabetes, cardiovascular disease, and major liver-related events. In parallel, chronic immune-mediated cholestatic liver diseases continue to pose important therapeutic challenges. Although ursodeoxycholic acid remains the standard first-line therapy for primary biliary cholangitis (PBC), and several second-line therapeutic options are now available, a substantial proportion of patients exhibit an incomplete biochemical response, while effective disease-modifying therapies for primary sclerosing cholangitis (PSC) remain lacking. Across etiologies, persistent metabolic stress, immune-mediated injury, and maladaptive fibrogenesis represent convergent pathogenic pathways. In MASLD, PPAR agonists have shown promising effects on steatosis, necroinflammatory activity, and fibrosis regression in randomized clinical trials, positioning them among the most advanced pharmacological strategies currently under investigation. In cholestatic liver diseases, selective and dual PPAR agonists have demonstrated significant improvements in cholestasis, pruritus, and markers of disease activity, supporting their role as second-line or adjunctive therapy. This review critically appraises the current preclinical and clinical evidence on the role of PPARs in CLDs, delineates the underlying molecular mechanisms, and discusses future therapeutic perspectives. Although the available evidence is encouraging, most clinical studies have primarily demonstrated improvements in surrogate biochemical and histological endpoints rather than hard clinical outcomes. Ongoing phase III trials and long-term outcome studies will be essential to define the role of PPAR agonists within future therapeutic algorithms for CLDs.