This systematic review/meta-analysis investigated the risks of fluoroquinolones (FQs) for aortic aneurysms (thoracic/abdominal) and Stanford A/B dissections.
We searched EMBASE, Ovid, PubMed, Web of Science, and Scopus databases in February 2024. Eligible observational studies were those that presented adjusted risk estimates for aortic aneurysm or dissection (AAD) incidence, aortic-specific mortality, or all-cause mortality in FQ-treated versus untreated unexposed populations.
A total of 13 studies were included (36,224,419 participants), eight of which were cohort studies, two were nested case-control studies, and three were case-crossover designs. FQ exposure was associated with significantly elevated de novo AAD risk within 30 days (relative risk (RR) = 3.40, 95% confidence interval (CI) = [2.72, 4.24]; heterogeneity: I2 = 41.5%, p = 0.11) and 60 days (RR = 3.53, 95% CI = [2.78, 4.49]; heterogeneity: I2 = 87.0%, p < 0.0001). The analysis also revealed a higher all-cause mortality risk for FQs versus non-exposed controls (odds ratio (OR) = 1.44, 95% CI = [1.08, 1.93]; heterogeneity: I2 = 0%, p = 0.80). Subgroup analysis demonstrated comparable aortic dissection (AD) and aortic aneurysm (AA) risks, except for a significantly increased de novo AA risk at 30 days (RR = 9.13, 95% CI = [6.05, 13.78]; heterogeneity: I2 = 68.7%, p = 0.07) and 60 days (OR = 1.69, 95% CI = [1.27, 2.26]; heterogeneity: I2 = 52%, p = 0.10).
This meta-analysis found a significant association between FQ use and short-term AAD risk. These results suggest that clinicians should weigh the risks of AAD before prescribing FQs, especially in patients with aortic vulnerability or pre-existing aortic pathology, considering alternative treatments when feasible.
CRD42024509853 (https://www.crd.york.ac.uk/PROSPERO/view/CRD42024509853).
This study aimed to investigate the application of machine learning (ML) in transcatheter aortic valve replacement (TAVR) and to demonstrate that, owing to the unique strengths of ML, this field outperforms conventional approaches in both preoperative assessment and postoperative prediction of TAVR. Nonetheless, TAVR is the preferred treatment option for medium- and high-risk patients with aortic stenosis, a common valvular disease, because of the associated minimally invasive nature and rapid recovery. However, challenges remain in preoperative evaluation and in predicting postoperative complications. Thus, ML technology offers innovative solutions for these challenges. This study provides an overview of current ML applications in TAVR and evaluates the associated benefits in measuring preoperative anatomical parameters and predicting postoperative complications. Indeed, the superiority of ML models for preoperative planning can be assessed by comparing ML model-derived data with measurements from senior and junior observers across various aortic root anatomical parameters. Additionally, this review discusses the challenges of applying ML in TAVR, including data acquisition, privacy protection, and model generalizability. The ongoing advancement of artificial intelligence (AI) technologies, particularly the integration of explainable AI and federated learning, is expected to enhance the accuracy and personalization of preoperative planning and postoperative prediction for TAVR. This progress will facilitate broader application of these technologies, ultimately benefiting a wider patient population.
Hypertrophic cardiomyopathy (HCM) is a common cardiovascular disease and one of the leading causes of exercise-induced sudden cardiac death in adolescents. HCM presents complex diagnostic, prognostic, and management challenges due to the phenotypic heterogeneity and clinical course. Artificial intelligence (AI), machine learning (ML), and deep learning (DL) technologies are expected to transform the roles of echocardiography, electrocardiography (ECG), and cardiac magnetic resonance (CMR) imaging in the clinical management of HCM. AI methods can fully integrate clinical and imaging data to enable a comprehensive assessment of the risk profile of a patient. However, challenges remain, such as insufficient data standardization across multiple sources, limited model interpretability, and data privacy issues. Despite these challenges, AI-based approaches have the potential to revolutionize the management of HCM by providing timely, accurate diagnoses and personalized treatment strategies based on individual patient risk profiles. This review systematically examines the current landscape of AI applications in HCM data analytics, with a focus on methodological advancements and clinical implementations. Furthermore, this review aims to facilitate the transition from experience-based to data-driven paradigms in HCM diagnosis, thereby advancing precision medicine and individualized patient management.
Patent foramen ovale (PFO) is the most common congenital heart defect and has been linked to migraines; however, the relationship between PFO and migraine remains controversial. This study aimed to evaluate whether percutaneous PFO closure alleviates migraines and explore the association between PFO and migraine.
Data from 5581 inpatients with PFO were collected between 2015 and 2020. A total of 71 stroke-free adults with PFO (45 with closure and 26 without) were included. Self-reported migraine history, frequency, and severity (0–10) were assessed. Outcomes were compared between patients with and without PFO closure, and logistic regression was used to examine the relationship between PFO closure and migraine improvement.
PFO closure significantly reduced migraine frequency and severity, with greater improvements observed after 2 years (p < 0.001). Logistic regression showed that PFO closure was associated with a higher likelihood of migraine improvement than non-closure (odds ratio (OR): 5.57, 95% confidence interval (CI): 1.76–17.68; p = 0.004). This association persisted after adjusting for multiple risk factors (p = 0.005).
Percutaneous PFO closure significantly improved migraines by reducing both frequency and severity, supporting a potential association between PFO and migraine.
Thoracic endovascular aortic repair (TEVAR) in Zone 2 frequently necessitates coverage of the isolated left vertebral artery (ILVA), a congenital vascular anomaly, to ensure adequate proximal sealing. However, the clinical requirement of ILVA revascularization remains uncertain. Thus, this study aimed to compare the outcomes between ILVA coverage and fenestration during Zone 2 TEVAR.
We retrospectively analyzed the clinical records of patients with ILVA who underwent Zone 2 TEVAR between September 2010 and August 2023. Patients were divided into two groups: Coverage Group (n = 23) and Fenestration Group (n = 33). Baseline characteristics, surgical outcomes, and changes in left and right vertebral artery diameters pre- and postoperatively were compared. Continuous variables were compared using Student's t-test or Mann-Whitney U test, depending on the distribution. Categorical variables were analyzed using the chi-square test or Fisher's exact test.
The overall cohort had a mean age of 54.48 ± 10.31 years, with 89.29% of participants male and a mean body mass index (BMI) of 25.88 ± 3.5 kg/m2. The Fenestration Group was significantly older than the Coverage Group (56.82 ± 8.78 vs. 51.13 ± 11.56; p = 0.04). Technical success of the TEVAR was achieved in both groups in 98.21% of cases, with no perioperative mortality. Simultaneous left subclavian artery stenting was performed more frequently in the Fenestration Group (57.58% vs. 21.74%; p = 0.008). At discharge, patients in the Coverage Group demonstrated a significantly greater reduction in left vertebral artery diameter compared with the Fenestration Group (13.64% [5.52%, 22.4%] vs. 0 [–3.29%, 5.13%]; p < 0.001). The incidence of vertebral artery diameter reduction was significantly higher in the Coverage Group compared with the Fenestration Group (39.13% vs. 6.06%; p < 0.01). Follow-up computed tomography angiography demonstrated a greater reduction in left vertebral artery diameter in the Coverage Group (52.94% vs. 14.29%; p = 0.020), while occlusion rates were comparable between groups (29.41% vs. 4.76%; p = 0.070).
Fenestration is associated with a lower incidence of postoperative ILVA diameter reduction compared with direct coverage during Zone 2 TEVAR. These findings highlight the potential benefit of ILVA revascularization and underscore the need for further validation in larger studies.
The Poly(ADP-ribose) polymerase (PARP) family comprises seventeen members that catalyze poly- or mono- adenosine diphosphate (ADP)-ribosylation, a pivotal post-translational modification regulating a wide array of cellular processes, including deoxyribonucleic acid (DNA) repair, apoptosis, protein synthesis, cellular proliferation, and responses to oxidative stress. PARP inhibitors (PARPIs) exhibit selective cytotoxicity in cancers with breast cancer susceptibility gene (BRCA) mutations or defects in homologous recombination. Activation of PARP, indicated by increased poly(ADP-ribose) (PAR) accumulation, is implicated in various disease states such as ischemia-reperfusion injury, vascular disorders, and diabetic complications. Clinically, PARPIs, in combination with anti-angiogenic therapies, not only show efficacy as monotherapies in epithelial ovarian cancer but also mitigate hypertension induced by anti-angiogenic agents. This review consolidates recent advancements in understanding the dual therapeutic potential of PARP inhibition, encompassing both antineoplastic and cardioprotective effects.
Inconsistent reports exist regarding the efficacy of using a concomitant intra-aortic balloon pump (IABP) among cardiac arrest (CA) patients undergoing extracorporeal cardiopulmonary resuscitation (ECPR). Thus, this review was conducted to summarize the prognoses of adult ECPR patients with concurrent IABP.
Data were gathered from PubMed, Embase, MEDLINE, Web of Science, and Cochrane databases. Cohorts of adult patients receiving ECPR with or without IABP, reporting short-term mortality, neurological outcomes, or extracorporeal membrane oxygenation (ECMO) weaning rates, were recruited. Characteristics of the study population and the above-mentioned outcomes were extracted. A random-effects model was used to pool the data. Subgroup analyses were conducted in the propensity score-matching (PSM) population.
Nine cohorts with 5260 adult ECPR patients were included. In-hospital/30-day mortality, neurological performances of survivors, and ECMO weaning outcomes were not significantly different between populations with and without IABP. Nevertheless, younger patients with IABP showed an apparent improvement in in-hospital/30-day mortality. Similar findings were demonstrated in the analyses of PSM cohorts. High heterogeneity was present in the total cohort.
In ECPR populations, concomitant IABP did not influence short-term survival, neurological, or ECMO weaning outcomes in the total cohort. However, IABP exhibited a survival benefit in the younger ECPR population. Further research in specific populations is warranted to validate and endorse our aggregated data.
CRD42024528761, Registration Link: https://www.crd.york.ac.uk/PROSPERO/view/CRD42024528761.
Coronary artery disease remains the leading cause of death worldwide, causing the field of myocardial revascularization to evolve rapidly. This review synthesizes current evidence and emerging trends, providing clinicians with practical guidelines to support decision-making in practice. Current drug-eluting stents have attained excellent safety profiles, with restenosis rates below 3%. Percutaneous treatment of complex lesions is now routinely feasible, with success rates of 90–95% in experienced institutions. Surgical revascularization remains the standard of care for complex multivessel disease, and total arterial grafting provides a strong long-term survival advantage. Nonetheless, emerging technologies, such as artificial intelligence (AI)-guided interventions, robotic interventions, and precision medicine strategies, have the potential to overcome current limitations and extend advanced therapies to high-risk patients. The optimal revascularization plan increasingly depends on integrating anatomical complexity, physiological significance, patient-specific features, and institution-specific expertise. Heart team-based decision-making is now a necessity, particularly in difficult cases where hybrid strategies might offer particular advantages. Over the coming decade, the extensive use of AI-assisted procedural planning, the broader adoption of minimally invasive treatments, and the establishment of prescription-based personalized medicine protocols are likely to be observed. Success will depend on addressing current challenges, including health disparities, delayed complications, and increasing heterogeneity in the patient population.
Sodium–glucose cotransporter 2 (SGLT2) inhibitors, employed as antidiabetic agents, have been shown to effectively improve the prognosis of patients with chronic and stable heart failure, chronic kidney disease, and diabetes in the context of cardiovascular–renal–endocrine integrated management. However, the safety and clinical benefits of the early application of SGLT2 inhibitors in hospitalized patients with acute heart failure remain controversial. This study aimed to evaluate the safety and prognostic impact of early SGLT2 inhibitor therapy in patients with acute heart failure.
A systematic literature search of the PubMed, Web of Science, and Cochrane Library databases was conducted to identify studies on the use of SGLT2 inhibitors in acute heart failure. Two researchers independently screened studies, extracted data, and assessed the risk of bias in the included studies. The meta-analysis was performed using STATA 16.0 software (StataCorp, College Station, TX, USA).
A total of 23 studies involving 47,291 patients with acute heart failure were included in this analysis (10 randomized controlled trials and 13 observational studies). Early use of SGLT2 inhibitors in hospitalized patients with acute heart failure was associated with a reduction in the incidence of composite events in the short term (relative risk (RR) = 0.64, 95% confidence interval (CI) (0.56, 0.74)), all-cause mortality (RR = 0.72, 95% CI (0.60, 0.86)), and heart failure rehospitalization rates (RR= 0.77, 95% CI (0.63, 0.87)); however, the early use of SGLT2i did not improve the incidence of cardiogenic death (RR = 0.74, 95% CI (0.51, 1.08)). Additionally, the early administration of SGLT2 inhibitors significantly reduced the incidence of cardiogenic mortality (RR = 0.77, 95% CI (0.60, 1.0); p = 0.045), as well as decreasing heart failure rehospitalization rates (RR = 0.77, 95% CI (0.70, 0.86)) and all-cause mortality (RR = 0.49, 95% CI (0.41, 0.60)), without increasing the incidence of adverse drug reactions such as acute kidney injury, urinary tract infections, diabetic ketoacidosis, hypoglycemia, or hypotension.
Early in-hospital use of SGLT2 inhibitors can safely and effectively reduce the incidence of all-cause mortality, cardiogenic rehospitalization, and composite events in acute heart failure patients in both the short term and over one year.
Participation and adherence to cardiac rehabilitation (CR) remain low worldwide; meanwhile, differences in barriers between industrialized and developing countries have not been well synthesized. A scoping review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) guidelines to map recent evidence (2014–2025) on barriers to CR participation and adherence in industrialized and developing settings. Searches conducted in major databases identified 538 records, of which 19 met the inclusion criteria for thematic analysis. Participation in CR ranged from 12.3% to 81% in industrialized countries and from 5% to 70% in developing settings, while adherence ranged from 70.8% to 90.3% and from 20.4% to 71.3%, respectively. Reported barriers can be clustered into patient-level beliefs and perceptions, logistical and work-related constraints, comorbidities and health status, socioeconomic and demographic factors, psychological characteristics, and health-system and environmental limitations. A wide variation in CR utilization persists globally, with distinct patterns of barriers across industrialized and developing contexts. These findings highlight the need for setting-specific strategies to improve CR participation and adherence.
The association between the modified cardiometabolic index (MCMI) and the risk of incident stroke across patients with different glycemic statuses remains unclear. This study aimed to investigate the relationship between baseline MCMI levels and incident stroke in Chinese middle-aged and older adults with varying glucose metabolism states.
Data were obtained from the China Health and Retirement Longitudinal Study (CHARLS) conducted in 2011, 2013, 2015, and 2018. Kaplan–Meier curves, multivariable Cox proportional hazards models, and restricted cubic spline analyses were employed to assess the relationship between the MCMI and stroke risk stratified by glycemic status. Subgroup and sensitivity analyses were performed to confirm the robustness of the findings.
A total of 7455 participants were included. A total of 457 individuals (6.13%) experienced stroke events during a median follow-up of 7 years. A significant linear association was observed between a higher MCMI and increased stroke risk. A nonlinear relationship was detected among participants with normal glucose regulation (NGR), with a sharp increase in risk beyond an MCMI threshold of 1.904 (hazard ratio (HR) = 1.85; 95% confidence interval (CI): 1.24–2.76; p = 0.003). An increased MCMI was also associated with increased stroke risk in individuals with prediabetes (HR = 1.34, 95% CI: 1.03–1.75) but not in individuals with diabetes. The associations varied across subgroups according to gender, residence, body mass index, and use of cardiovascular medications. Sensitivity analyses supported the stability of the results.
An elevated MCMI is positively associated with incident stroke, particularly in individuals with NGR or prediabetes. Early identification of a high MCMI may be valuable for stroke prevention, risk stratification, and timely intervention in community populations.
Chronic heart failure (CHF) is a common clinical syndrome characterized by reduced exercise capacity, diminished quality of life (QoL), and unfavorable cardiovascular outcomes. Conventional cardiac rehabilitation often requires moderate-to-high-intensity exercise, which may be tolerated poorly by many CHF patients. Low-intensity mind–body interventions, such as traditional Chinese exercises (TCEs), are potentially more suitable; however, the evidence from existing studies is fragmented and sometimes inconsistent. Thus, this study aimed to conduct an umbrella review of systematic reviews (SRs) and meta-analyses (MAs) to evaluate the effectiveness of TCEs in improving exercise capacity, QoL, and cardiovascular function in patients with CHF.
An umbrella review of SRs/MAs was conducted by searching English and Chinese databases without language limits and focusing on randomized controlled trials (RCTs) that assessed the additional benefit of TCEs in individuals with CHF. Methodological quality was appraised using the A Measurement Tool to Assess Systematic Reviews 2 (AMSTAR 2) checklist and the Risk of Bias in Systematic Reviews (ROBIS) instrument. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system was utilized to quantify the certainty of evidence. Individual trial data were retrieved, and re-meta-analyses were performed using standard statistical procedures, with publication bias assessed via Egger's test.
A total of 15 SRs/MAs were included, encompassing 65 original trials. Our re-meta-analysis indicated that TCEs were associated with substantially longer 6-minute walk test (6-MWT) values, improved QoL measured by the Minnesota Living with Heart Failure Questionnaire (MLHFQ), higher left ventricular ejection fraction (LVEF), reduced B-type natriuretic peptide (BNP) levels, and enhanced maximal oxygen consumption (VO2max). Baduanjin exhibited a particularly robust effect on lowering N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentrations, while Yijinjing yielded comparatively greater improvements in VO2max. Nonetheless, limitations such as suboptimal methodological quality and overlapping study samples require cautious interpretation.
TCEs may serve as a beneficial adjunct to standard care for CHF, improving exercise capacity, QoL, and key cardiac markers. Large, rigorous RCTs with extended follow-up are needed to confirm the durability of TCEs and further define the role of these exercises in comprehensive CHF rehabilitation.
CRD420251003129 (https://www.crd.york.ac.uk/PROSPERO/view/CRD420251003129).
Coronary artery ectasia (CAE) is characterized by abnormal, localized, or diffuse dilatation of the coronary vasculature and is an increasingly recognized anatomical entity encountered during coronary angiography. Although often associated with atherosclerosis, the exact pathogenesis of CAE remains unknown; hence, an optimal management strategy is difficult to establish and remains highly controversial due to a lack of high-quality randomized controlled trial evidence. Current therapeutic modalities include medical therapy, percutaneous coronary intervention (PCI), and surgical options. We present a review, supported by a representative case of ST-elevation myocardial infarction (STEMI) in a patient with CAE, as a systematic summary of the clinical and angiographic features of the condition. We discuss contemporary treatment approaches, especially how to navigate antithrombotic strategies and the role of intravascular ultrasound (IVUS)-guided PCI.
The clinical value of B-type natriuretic peptide (BNP) or N-terminal pro-B-type natriuretic peptide (NT-proBNP)-guided therapy for improving outcomes in patients with heart failure (HF) remains controversial. Thus, this meta-analysis synthesizes the available evidence from randomized controlled trials (RCTs) to determine whether a biomarker-guided strategy reduces all-cause mortality and HF-related hospitalizations compared with clinically guided management.
This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We conducted a systematic search of PubMed, Embase, the Cochrane Library, and Web of Science databases from inception to May 2025 for RCTs comparing biomarker-guided versus clinically guided management in patients with HF. Pooled risk ratios (RRs) were calculated using a random-effects model. We performed extensive supplementary analyses, including a subgroup analysis, sensitivity analysis, and trial sequential analysis (TSA).
We included 17 articles (reporting on 17 distinct RCTs) comprising 5069 patients. The primary meta-analysis showed that biomarker-guided therapy was associated with a significant reduction in all-cause mortality (RR 0.84, 95% confidence interval (CI) 0.73–0.96; I2 = 12.2%) and HF-related hospitalizations (RR 0.79, 95% CI 0.65–0.96; I2 = 53.7%). However, the robustness of these findings was undermined by subsequent analyses. Meanwhile, a sensitivity analysis restricted to studies with a low risk of bias rendered the mortality benefit non-significant (RR 0.90, 95% CI 0.79–1.03). Egger's test indicated potential publication bias (p = 0.0285), and TSA suggested the cumulative evidence was insufficient to draw a definitive conclusion.
Although there is a trend toward benefit, the existing evidence for biomarker-guided HF therapy is deemed “very low” quality based on the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) assessment. The results were compromised by methodological deficiencies in primary studies and potential publication bias. Therefore, the evidence is inadequate to support the routine use of this strategy in clinical practice. Further large-scale, high-quality RCTs are warranted.
CRD420250652134, https://www.crd.york.ac.uk/PROSPERO/view/CRD420250652134.
Heart failure (HF) is steadily increasing in prevalence and poses a major global health challenge, with substantial medical and economic burdens. HF represents the terminal stage of diverse cardiac disorders and is characterized by poor prognosis despite the availability of conventional pharmacological treatments, underscoring the urgent need for novel therapeutic approaches. Accumulating evidence highlights a strong association between HF and mitochondrial dysfunction, of which dysregulated mitochondrial calcium (mCa2+) homeostasis plays a pivotal role in disease pathogenesis. Ca2+ serves as an essential signaling messenger that regulates energy metabolism and also governs cell survival and myocardial contractility. Thus, this review introduces the mechanisms of mCa2+ uptake and efflux and the association of these processes with HF and emerging therapeutic strategies. We also discuss mCa2+ uniporter (MCU) inhibitors and Elamipretide, a mitochondria-targeted peptide. Collectively, this work provides novel insights and preclinical evidence supporting mitochondria-based interventions for HF.
Residual cardiovascular risk remains substantial despite aggressive low-density lipoprotein cholesterol (LDL-C) lowering in coronary heart disease (CHD). Consequently, this elevated risk has spurred the search for non-lipid targets, such as homocysteine (HCY). However, the combined effect of HCY with LDL-C and the overall potential for combined risk stratification remain unclear.
This retrospective cohort study included patients with CHD confirmed by coronary angiography or computed tomography angiography at the General Hospital of Ningxia Medical University between January 2019 and December 2021. Participants were stratified by baseline LDL-C levels (<1.8 vs. ≥1.8 mmol/L) and HCY (<15 vs. ≥15 μmol/L). Major adverse cardiovascular events (MACEs) were employed as the primary endpoint, defined as a composite of all-cause death, stroke, non-fatal myocardial infarction, or unplanned revascularization.
A total of 744 MACEs were recorded during the 25-month follow-up. Elevated levels of LDL-C (adjusted hazard ratio (aHR) = 1.38, 95% confidence interval (CI): 1.09–1.73) and HCY (aHR = 1.47, 95% CI: 1.19–1.81) were independently associated with a higher risk of MACEs. The risk was synergistic when both factors were elevated, as patients in the high LDL-C and high HCY group had a significantly increased risk (aHR = 1.97, 95% CI: 1.34–2.90) compared to the reference group with low levels.
LDL-C and HCY are independent predictors of MACEs in patients with CHD, and the combined use of these indices improves risk stratification. Thus, integrating these indices into clinical practice could improve personalized management strategies and outcomes in this high-risk population.
Hematuria is a frequent urological presentation, particularly in patients with significant cardiovascular comorbidities who receive dual antiplatelet therapy (DAPT) after acute coronary syndrome (ACS). Managing hematuria in this high-risk population poses a unique clinical challenge, requiring a careful balance between thrombotic and bleeding risks. This review summarizes current evidence and provides practical recommendations for the multidisciplinary management of hematuria in patients on antiplatelet medications following ACS. Relevant literature and international guideline recommendations from urology, cardiology, and emergency medicine were reviewed, focusing on diagnostic evaluation, hemodynamic assessment, modification of antiplatelet therapy, surgical considerations, and reversal strategies. The management pathway begins with a prompt assessment of hemodynamic stability, hematuria severity, and underlying cause. Conservative measures include catheterization, bladder irrigation, and correction of coagulation disorders. The diagnostic evaluation should not be delayed, as up to 24% of cases of visible hematuria in this population are due to malignancy. Antiplatelet management depends on bleeding severity and thrombotic risk: mild bleeding generally allows continuation of DAPT; moderate bleeding may warrant temporary cessation of aspirin; severe bleeding often requires de-escalation to monotherapy; life-threatening bleeding necessitates immediate discontinuation of all antiplatelets. Interventional options—ranging from endoscopic clot evacuation to selective arterial embolisation—should be tailored to the stability and cardiovascular risk of the patient. Resumption of antiplatelet therapy should occur as early as clinically feasible, ideally within 48 hours, with de-escalated regimens considered for patients with a high bleeding risk. Hematuria in post-ACS patients on antiplatelets requires an individualized, multidisciplinary approach to optimize hemostasis without compromising cardiovascular protection. Early diagnosis of underlying urological pathology is essential, and both bleeding severity and ischemic risk should guide antiplatelet modification therapy. Evidence supports early specialist involvement, adherence to structured risk-adapted protocols, and judicious use of conservative or interventional measures to improve outcomes.
Dystrophin deficiency is the core pathological feature of Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD). Indeed, a deficiency in dystrophin results in the progressive degeneration of skeletal muscle and severely compromises the structure and function of cardiomyocytes, eventually leading to dilated cardiomyopathy and heart failure. Thus, this review provides an in-depth analysis of the molecular mechanisms underlying dystrophin-deficient cardiomyopathy, including membrane instability, calcium dysregulation, mitochondrial dysfunction, and fibrosis. The role of inflammatory responses in disease progression is also discussed. In addition, we evaluate current and emerging therapeutic strategies, including gene therapy, pharmacological interventions, and regenerative medicine approaches, and highlight recent preclinical and clinical trial data. Finally, we explore future directions in precision medicine, novel biomarkers for early detection, and combination treatment regimens, to provide a comprehensive resource for clinicians and researchers working in this challenging field.
The prognosis and long-term survival of high-risk coronary syndrome patients with pulmonary hypertension (PH) remain unsatisfactory, and limited research has evaluated the synergistic therapeutic effects of endothelin receptor antagonists (ERAs) combined with soluble guanylate cyclase agonists (sGCAs). This study aimed to assess the synergistic cardiopulmonary protective effects and clinical safety of ERA combined with sGCA therapy in patients with high-risk coronary syndrome complicated by PH.
This retrospective controlled study included 132 patients with high-risk coronary syndrome and PH who were admitted between January 2019 and December 2023. After exclusion criteria were applied, 119 patients were analyzed and categorized into a control group (ambrisentan monotherapy, n = 58) and an experimental group (ambrisentan plus riociguat, n = 61) according to the associated treatment strategy. Primary endpoints included 6-minute walk distance (6MWD), N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels, and the World Health Organization-related functional class (WHO-FC). Secondary endpoints included cardiac index (CI), left ventricular end-diastolic diameter (LVEDD), tricuspid annular plane systolic excursion (TAPSE), mean pulmonary artery pressure (mPAP), pulmonary vascular resistance (PVR), Borg dyspnea score (BDS), and the incidence of adverse events.
Baseline characteristics between the two groups were comparable (all p > 0.05). Following treatment, the 6MWD, CI, and TAPSE values significantly improved in both groups (all p < 0.05), with greater improvements observed in the experimental group (95% CI: –3.61 to –0.05, p = 0.044; 95% CI: –0.20 to –0.004, p = 0.039; 95% CI: –0.29 to –0.07, p = 0.001). The NT-proBNP, LVEDD, mPAP, PVR, and BDS values decreased in both cohorts (all p < 0.05), with more pronounced reductions in the experimental group (95% CI: 0.02–3.5, p = 0.048; 95% CI: 0.03–0.21, p = 0.012; 95% CI: 0.02–2.03, p = 0.046; 95% CI: 0.65–4.30, p = 0.008; 95% CI: 0.06–0.78, p = 0.022). The proportion of individuals in the WHO-FC classes III–IV was lower in the experimental group (95% CI: 1.05–4.56, p = 0.035). No statistically significant difference in adverse-event incidence was observed between groups (95% CI: 0.73–5.03, p = 0.184).
Combination therapy with ambrisentan and riociguat effectively improved cardiopulmonary function and clinical outcomes in patients with high-risk coronary syndrome and PH, offering a promising therapeutic strategy for this population. This study is a single-center retrospective study, which inherently limits the credibility of causal inference; therefore, the results need to be further verified by multi-center, large-sample prospective studies.
Pulsed field ablation (PFA) has emerged as a promising non-thermal energy source for treating atrial fibrillation (AF), demonstrating comparable efficacy to traditional thermal ablation techniques while offering an improved safety profile. However, recent evidence suggests that PFA may be associated with intravascular hemolysis, a complication that can potentially lead to acute kidney injury (AKI). This review aims to provide a comprehensive overview of the mechanisms of hemolysis associated with PFA and to summarize current strategies to mitigate the risk of AKI. The delivery of high-voltage electrical pulses during PFA can induce red blood cell lysis, resulting in elevated circulating free hemoglobin. The extent of hemolysis has been shown to correlate with several procedural variables, including peak output voltage, catheter-tissue contact quality, and, particularly, the number of energy applications delivered. Recent studies have highlighted that adequate preprocedural hydration may effectively reduce the incidence of AKI by promoting renal clearance of hemolytic products. Although hemolysis appears to be an unavoidable effect of pulsed field ablation, the clinical consequences associated with hemolysis, particularly AKI, can be significantly reduced with preventive measures.
Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9is) have emerged as a promising class of medications, primarily recognized for inducing potent cholesterol-lowering effects. In addition to the established role of these inhibitors in reducing low-density lipoprotein cholesterol levels, recent studies suggest that PCSK9is may also modify coronary atherosclerotic plaques. Therefore, this meta-analysis aimed to comprehensively synthesize data from relevant clinical studies and trials investigating the effects of PCSK9is on coronary atherosclerotic plaque characteristics.
We performed a literature search for studies assessing the evolution of coronary atherosclerotic plaques after treatment with a PCSK9i compared with a control group. We excluded reviews, editorials, case reports/case series, and studies that did not use PCSK9is or lacked a control group. The main outcomes of interest were changes in percent atheroma volume (PAV), total atheroma volume (TAV), minimal fibrous cap thickness (FCT), lipid arc, and the number of patients with improved PAVs at follow-up. Effect sizes are presented as a standardized mean difference (SMD) or risk ratio (RR) alongside the corresponding 95% confidence intervals (CIs) and were pooled based on a random-effects model. Publication bias was assessed by funnel plot inspection and Egger's regression test.
The literature search yielded 142 results. After applying the exclusion criteria, nine studies were selected for data extraction and inclusion in the meta-analysis. Concerning the intravascular ultrasound findings, PCSK9is significantly reduced the TAV (MD –7.09 mm3, 95% CI –11.36 to –2.81; p = 0.01) and induced non-significant reductions in the PAV (MD –1.91%, 95% CI –5.08 to 1.25; p = 0.17); meanwhile, a greater proportion of patients treated with PCSK9 inhibitors exhibited an improvement in the PAV (RR 1.30, 95% CI 1.19 to 1.42; p < 0.001). For optical coherence tomography parameters, patients treated with PCSK9 inhibitors showed an increase in minimal FCT (MD 36.25 μm, 95% CI 0.75 to 71.75; p = 0.047) and a non-significant decrease in lipid arc (MD –17.64°, 95% CI –49.73 to 14.44; p = 0.14).
This meta-analysis suggests that PCSK9i therapy may be associated with modest favorable changes in selected intravascular imaging markers of coronary atherosclerotic plaque burden and stability.
Coronary artery calcification (CAC) is a strong predictor of long-term adverse outcomes in patients with coronary artery disease (CAD). Meanwhile, insulin resistance (IR) is a key metabolic disorder that accelerates CAC progression through multiple pathways. Fibroblast growth factor 21 (FGF21) improves glucolipid metabolism and has been associated with vascular calcification. However, the relationship between serum FGF21 level and CAC severity in patients with varying degrees of IR remains unclear.
A total of 128 patients with CAD who underwent preprocedural coronary computed tomography angiography and percutaneous coronary intervention were enrolled. Patients were stratified by triglyceride–glucose (TyG) index into high (TyG >8.62, n = 62) and low (TyG ≤8.62, n = 66) groups. Associations between FGF21 levels and severe CAC were analyzed under varying degrees of IR.
In patients with a TyG index >8.62, serum FGF21 levels were significantly lower in those with severe CAC, and were negatively correlated with CAC scores. Multivariable analysis revealed that serum FGF21 levels were independently associated with severe CAC (odds ratio (OR) per 1-standard deviation (SD) increase: 0.261; 95% confidence interval (CI): 0.073, 0.933; p < 0.05). In contrast, serum FGF21 levels among patients with a TyG index ≤8.62 did not differ significantly between the severe and non-severe CAC groups, and no independent association between serum FGF21 level and severe CAC was observed after adjustment. Importantly, a significant interaction was observed between the TyG index and FGF21 level (p for interaction = 0.035). Moreover, the protective association between FGF21 and CAC was primarily observed in patients with a high TyG index.
Lower serum FGF21 levels in patients with CAD can identify individuals at increased risk of severe CAC, particularly among those with a higher degree of IR. Serum FGF21 levels may serve as a novel biomarker for CAC risk stratification in metabolically susceptible patients.
The neutrophil-to-lymphocyte ratio (NLR) has been linked as a marker of systemic inflammation to adverse outcomes in various metabolic diseases. However, the association of the NLR with mortality risk among patients with hyperlipidemia remains inconclusive. Thus, this research aimed to investigate whether the NLR is associated with mortality risk among individuals with hyperlipidemia and to examine how glycemic status influences this relationship.
Weighted Cox regression, restricted cubic splines (RCS), and subgroup analyses were employed to evaluate the association between the NLR and mortality risk in patients with hyperlipidemia. Time-dependent receiver operating characteristic (ROC) analysis was conducted to assess the predictive accuracy for mortality risk.
In Model 3, individuals in the highest NLR quartile had a 40% higher risk of all-cause mortality (95% confidence interval (CI): 1.19–1.65; p for trend <0.001) and an 86% higher risk of cardiovascular mortality (95% CI: 1.28–2.68; p for trend <0.001) compared with those in the lowest quartile. Time-dependent ROC analysis confirmed the superior performance of the NLR in predicting cardiovascular mortality risk. A significant interaction between the NLR and diabetes mellitus (DM) was observed for both all-cause and cardiovascular mortality in the subgroup analyses. Given this finding, we further examined the association between the NLR and mortality, stratified by glycemic status. The results indicated that the association between the NLR and mortality was stronger among individuals with DM.
An elevated NLR is closely associated with an increased risk of mortality among individuals with hyperlipidemia, and the presence of DM significantly strengthens this association.
Mitral valve transcatheter edge-to-edge repair (M-TEER) has evolved from a highly specialized intervention to an essential treatment option for patients with severe mitral regurgitation (MR) who are unsuitable candidates for surgery. Moreover, current guidelines support the use of M-TEER in both secondary MR and selected cases of primary MR. In addition to these established indications, data from clinical trials and registries indicate that M-TEER is associated with improved short-term outcomes compared with conservative therapy in acute MR after myocardial infarction, and is beneficial in more complex scenarios, such as advanced heart failure, hypertrophic obstructive cardiomyopathy, and mitral annulus calcification. Meanwhile, combined strategies, such as repairing the mitral and tricuspid valves simultaneously, adding M-TEER to transcatheter aortic valve replacement, or performing this procedure alongside left atrial appendage closure, are gaining ground as practical ways to address the broader needs of these high-risk patients. More recently, M-TEER has been used in patients with moderate MR, as this stage is now recognized to be associated with adverse outcomes. Overall, current evidence supports M-TEER as a safe and versatile therapy across an expanding range of clinical scenarios. Nonetheless, ongoing studies will help further clarify long-term outcomes and refine patient selection.
This study aimed to explore the association between serum lipoprotein(a) [Lp(a)] levels and recurrent acute coronary syndrome (ACS) and revascularization of target lesions in patients with ACS who showed no functional ischemia on fractional flow reserve (FFR) testing during coronary angiography (CAG).
The retrospective observational study was conducted at the General Hospital of Northern Theater Command and included 513 patients with new ACS recruited from 23 February 2016 to 6 November 2023 and followed up. These patients underwent CAG examination and were found to have at least one coronary artery with moderate or greater stenosis, and also underwent FFR measurement with FFR value >0.80. Patients experienced recurrent ACS and underwent unplanned revascularization were defined as the revascularization group, while patients did not experience recurrent ACS and undergo unplanned revascularization were assigned to the no revascularization group. The study employed propensity score matching (PSM) and receiver operating characteristic (ROC) curve analysis to evaluate the correlation between serum Lp(a) and recurrent ACS and unplanned revascularization in target lesion with FFR value >0.80.
Serum Lp(a) levels were higher in female patients. There were no statistically significant differences in the basic clinical characteristics, medication use, laboratory test results or ejection fraction values between the two groups. During a average follow-up of 6.5 years, 119 patients (23.2%) experienced recurrent ACS and unplanned revascularization in the target lesion. The level of serum Lp(a) in the patients that underwent unplanned revascularization was significantly higher than in the group that did not undergo repeated revascularization (65.80 mmol/L vs. 60.57 mmol/L, p = 0.034).
Serum Lp(a) is an independent risk factor for recurrent ACS and unplanned revascularization in patients with ACS and FFR negative plaque.
The role of biological aging in the progression of atrial fibrillation (AF) remains unclear. Therefore, the present study aimed to investigate the influence of biological aging markers on transitions from health to AF, complications, and death.
Two UK Biobank datasets were analyzed: 260,198 participants for the Klemera-Doubal method for biological age (KDM-BA) and PhenoAge analyses, and 339,603 for telomere length analyses, excluding those with AF, complications (heart failure, myocardial infarction, cerebral infarction, dementia, and arterial embolic diseases) at baseline. The present study employed a multi-state model to evaluate the associations between biological aging markers and the progression of AF. Mediation analyses were utilized to assess the role of systemic inflammation.
During the follow-up period, 9.51–9.67% of patients in the two datasets developed AF, among whom 17.59–17.85% progressed to complications, with 8.20–10.83% of these patients dying from AF-related complications. In comparison with Q1, Q4 of the KDM-BA and PhenoAge analyses was associated with elevated risks across transitions, particularly from baseline to AF (hazard ratios (HR): 1.09, 95% confidence interval (CI): 1.04–1.14; HR: 1.30, 95% CI: 1.25–1.35), baseline to death (HR: 1.10, 95% CI: 1.04–1.16; HR: 1.11, 95% CI: 1.06–1.16), and AF to complication (HR: 1.75, 95% CI: 1.58–1.94; HR: 1.52, 95% CI: 1.37–1.68). Moreover, Q4 of the telomere length analyses showed protective effects against AF onset (HR: 0.83, 95% CI: 0.80–0.86), progression to complications (HR: 0.78, 95% CI: 0.72–0.84), and from baseline to death (HR: 0.91, 95% CI: 0.88–0.94). Systemic inflammation was associated with up to 29.95% of these associations.
Associations were found between biological aging markers (higher KDM-BA and PhenoAge, and shorter telomere length) and the risk of AF transitions, particularly with respect to an increased risk of AF and progression to complications. These findings underscore the importance of biological age in AF risk stratification and prevention.
Residual inflammation and persistent lipid abnormalities substantially increase the risk of adverse clinical outcomes in patients with acute myocardial infarction (AMI) undergoing primary percutaneous coronary intervention (PPCI). Although proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors have been shown to improve cardiovascular outcomes, the efficacy, safety, and prognosis of these inhibitors when administered as a single dose after PPCI in real-world practice remain unclear.
A retrospective study of patients with acute ST-segment elevation myocardial infarction (STEMI) admitted between May 2023 and May 2024. Patients were assigned to an alirocumab group or a conventional treatment group based on whether a single dose of alirocumab was administered within 6 hours of PPCI. Baseline differences between groups were balanced using 1:1 propensity score matching (PSM). The occurrence of major adverse cardiovascular events (MACEs) at 12 months post-procedure was applied as the primary endpoint. Secondary endpoints included lipid profiles, inflammatory markers, cardiac function, quality-of-life changes, and safety outcomes.
A non-significant downward trend in the incidence of MACEs at 12 months post-PPCI was observed in the alirocumab group compared with the conventional treatment group (log-rank p = 0.242). A single dose of alirocumab significantly reduced low-density lipoprotein cholesterol (LDL-C) at 1 month (p = 0.011) and attenuated inflammation markers at 24 hours postoperatively. At 12 months, the alirocumab group showed improved cardiac function with significantly reduced left ventricular end-systolic volume (LVESV, p = 0.009) and modest but statistically significant improvement in quality of life (p = 0.012), primarily driven by enhanced physical activity (p < 0.001), alongside reduced insecurity (p < 0.001). No increased incidence of adverse events was observed (p > 0.05).
This study demonstrated that a single dose of alirocumab in STEMI patients undergoing PPCI was associated with significant improvement in LDL-C levels, attenuation of early postoperative inflammation, and a favorable trend toward improved cardiac function and quality of life, while maintaining an acceptable safety profile.
Myocardial stiffness is a central determinant of diastolic dysfunction and clinical outcomes in hypertrophic cardiomyopathy; however, a non-invasive evaluation of myocardial stiffness remains challenging. Emerging techniques, such as elastography, offer direct, non-invasive quantification of myocardial stiffness, providing critical insights beyond conventional indirect surrogates. This review summarizes the principles, validation, and clinical evidence for current non-invasive techniques for assessing myocardial stiffness. We further discuss the clinical applications of these techniques in hypertrophic cardiomyopathy, including diagnostic refinement, fibrosis detection, risk stratification, and treatment monitoring, as well as the challenges and future directions required for broader clinical translation. Ultimately, the non-invasive assessment of myocardial stiffness holds promise for transforming patient management to phenotyping and therapeutic decision-making through a more precise, mechanism-based approach.
Care processes and outcomes for patients undergoing primary percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI) remain heterogeneous. A “patient pathway” framework—defined as the sequence of clinically relevant events from symptom onset through diagnosis, reperfusion, and early recovery—can help identify real-world points of failure and opportunities for system-level improvement. In this narrative review, we contrast an “ideal” STEMI pathway with the pathways commonly observed in routine practice for patients treated with primary PCI, and we contextualize deviations from best practice from patient, clinician, health service, and societal perspectives. From the patient's perspective, the priority is rapid symptom recognition and seeking care; however, delays are frequent, particularly in individuals with mild, atypical, or non-classical presentations, prolonging total ischemic time and increasing myocardial injury. Clinicians aim to diagnose STEMI promptly and initiate evidence-based therapy and reperfusion without delay, yet diagnostic uncertainty and competing differentials can contribute to missed or late diagnoses. Health systems seek to provide timely, efficient, and cost-effective emergency revascularization, but performance is influenced by pre-hospital logistics, triage, catheterization laboratory availability, and inter-hospital transfer processes. At the societal level, STEMI imposes substantial mortality, morbidity, and economic burden through premature death and disability. We synthesize evidence on delays to revascularization, misdiagnosis, populations at risk for atypical presentation, and pragmatic interventions to improve care. We conclude that pathway-based analyses offer a structured approach to defining desirable STEMI care trajectories and to reducing missed opportunities for better outcomes.
Disparities exist in the representation of genders in cardiovascular clinical trials. Atrial fibrillation (AF) is associated with significant morbidity and mortality; however, understanding regarding the representation of women in AF-related clinical trials remains limited. Therefore, this systematic review sought to evaluate the representation of women in AF-related clinical trials.
We conducted a systematic review of clinical trials using the PubMed, Scopus, and EMBASE databases from 1996 to January 1st, 2024, focusing on AF-related lifestyle interventions, pharmacological treatments, catheter ablation, and device therapies for AF. Data extraction and analysis encompassed trial characteristics, participant demographics, and funding sources. The primary outcome was the prevalence of female enrollees, quantified through participation-to-prevalence ratios (PPRs). This was estimated overall and stratified by funding source, intervention type, and enrollment region.
Of the 103 clinical trials involving 218,322 participants (39.5% female), the PPR ranged from 0.00 to 1.73, with an average PPR of 1.03. Meanwhile, 43% of the trials exhibited female under-representation (PPR, <0.8). University-funded trials showed higher female enrollment (mean PPR, 0.951) compared to industry/government-funded trials (mean PPR, 0.800). No differences were observed in the representation of women when comparing enrollment regions or intervention types.
Despite advancements in AF management, gender disparities persist in AF-related clinical trial representation, particularly in industry/government-funded studies compared to university-funded trials. Thus, addressing implicit biases and enforcing sex equality guidelines are critical steps toward more inclusive cardiovascular research.
Abdominal aortic aneurysm (AAA) is less prevalent in women, yet rupture occurs owing to smaller diameters, leading to higher mortality rates; moreover, higher mortality rates also occur in women after aneurysm repair procedures. Meanwhile, whether women derive comparable benefit from endovascular aneurysm repair (EVAR) remains uncertain, partly because of anatomical constraints, such as smaller-caliber access vessels and more angulated proximal necks. This review evaluates sex-specific perioperative and long-term outcomes after EVAR.
This study was conducted as a systematic review with narrative synthesis, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 framework. A comprehensive search was conducted in the PubMed/MEDLINE and Scopus databases for studies published between January 2000 and September 2025. Search strings combined controlled vocabulary and free-text terms for “abdominal aortic aneurysm”, “endovascular aneurysm repair”, and “sex” or “gender” or “female”. A predefined Population, Intervention, Comparison, Outcome (PICO) model was used to guide study selection. Comparative observational cohorts, registry or claims analyses, and EVAR-focused meta-analyses reporting sex-stratified outcomes were eligible. Articles were restricted to English. Outcomes included perioperative mortality, major complications, reintervention, and long-term survival. Given the heterogeneity and the availability of recent pooled analyses, quantitative synthesis favored adjusted estimates from high-quality meta-analyses and registries, and no new pooled meta-analysis was performed to avoid data duplication.
A total of 15 studies met the inclusion criteria, encompassing more than 500,000 EVAR procedures. Women consistently exhibited higher early mortality and morbidity after standard infrarenal EVAR. The largest EVAR-focused meta-analysis reported an odds ratio (OR) for 30-day mortality of 1.73 (95% confidence interval (CI) 1.32–2.26) and in-hospital mortality OR of 1.90 (1.43–2.53) for women versus men, with increased risks of limb ischemia (~2.4-fold), renal (OR ~1.7), and cardiac complications (OR ~1.7). Long-term all-cause mortality was higher in women (hazard ratio (HR) 1.23, 95% CI 1.09–1.38). Contemporary registry data indicated similar adjusted mortality but persistently greater access-related morbidity in women, including higher rates of limb ischemia (5.3% vs. 3.2%) and major bleeding (22.0% vs. 15.9%). Perioperative mortality and complications were approximately two-fold higher in women following complex EVAR, defined as fenestrated and/or branched endovascular repair (F/BEVAR) for juxtarenal, pararenal, suprarenal, or thoracoabdominal aneurysms. Additionally, survival remained inferior in those with a ruptured AAA (8-year survival: 36.7% vs. 49.5%).
Women undergoing EVAR continue to experience higher perioperative morbidity and less favorable long-term outcomes compared with men, despite advances in device technology and perioperative care. These disparities largely reflect anatomical and physiological differences, delayed presentation, and underrepresentation in clinical trials and registries. This systematic review and narrative synthesis clarifies sex-specific differences in outcomes after standard infrarenal EVAR and complex F/BEVAR, integrating evidence from contemporary device eras. Sex-aware imaging, individualized access planning, and device design tailored to smaller anatomy are critical to achieving equitable outcomes in endovascular aortic repair.
Heart failure (HF) is a multifaceted clinical syndrome that frequently precipitates disturbances in perfusion, ventilation, and metabolic regulation, all of which are rapidly detectable through arterial blood gas (ABG) analysis. Meanwhile, clinical markers such as lactate, arterial pH, arterial partial pressure of carbon dioxide (PaCO2), arterial partial pressure of oxygen (PaO2), bicarbonate, and electrolyte concentrations provide dynamic insight into the pathophysiologic status of patients and can serve as early indicators of decompensation. This review evaluates the clinical significance of key ABG and electrolyte parameters in both acute and chronic HF, emphasizing the prognostic value of the analyses, contribution to risk stratification, and utility in guiding therapy. In acute HF and cardiogenic shock, hyperlactatemia and acidosis are associated with increased mortality and the need for hemodynamic or ventilatory support. Furthermore, electrolyte abnormalities, particularly those involving sodium and potassium, are common and driven by neurohormonal activation, pharmacological therapies, and volume shifts. Therefore, integrating ABG and electrolyte monitoring into routine HF management can enhance diagnostic precision and support timely, targeted interventions. This narrative review synthesizes current evidence and proposes a practical framework for interpreting ABG results in the context of contemporary HF care.
Pulmonary arterial hypertension (PAH) is the most serious complication of congenital heart disease (CHD), constituting a heterogeneous clinical entity classified within Group 1 of the Clinical Classification of Pulmonary Hypertension (PH). PAH associated with congenital heart disease (PAH-CHD) affects approximately 3–10% of patients with CHD and accounts for up to one-third of all PAH cases in the adult population. This review provides an educational and up-to-date perspective on the epidemiology, pathophysiology, diagnosis, and management of PAH-CHD. The updated haemodynamic definitions of the 2022 European Society of Cardiology (ESC)/European Respiratory Society (ERS) guidelines (mean pulmonary artery pressure (PAP) ≥20 mmHg) and the importance of contemporary registries (COMPERA-CHD, HOPE) in defining prognosis are discussed. The pathophysiology is explored in depth, from initial shear stress to the imbalance in the three canonical pathways that regulate pulmonary vascular functions (endothelin, nitric oxide, prostacyclin), the role of inflammation and metabolism, and the central importance of the TGF-β/BMPR2 genetic pathway, which has led to new disease-modifying therapies. Moreover, this review addresses the crucial clinical distinction between paediatric management, constrained by limited evidence, and adult management (ACHD), with a focus on the multisystem disorder of Eisenmenger syndrome (ES) and the challenges of care transition. The gold-standard diagnostic (right heart catheterisation), the ‘treat and repair’ strategy in the haemodynamic ‘grey zone’, and the complex risk stratification in this population are also analysed. Additionally, the evidence from key trials (BREATHE-5, MAESTRO, REPLACE) and the paradigm shift towards initial combination therapy (AMBITION) are reviewed from a therapeutic perspective. Finally, the most significant advance is highlighted: Sotatercept, a vascular remodelling reversal agent (STELLAR study), concluding with a review of chronic complications and prospects in the field.
Aortic dissection (AD) is a cardiovascular emergency with high mortality; however, the underlying molecular pathophysiology of AD remains incompletely understood. Pyroptosis, a proinflammatory form of programmed cell death, contributes to vascular injury; nonetheless, the upstream transcriptional regulation of pyroptosis in AD is similarly poorly defined.
Differentially expressed genes were identified in aortic tissues from AD patients (Gene Expression Omnibus (GEO) datasets) using bioinformatics analyses, with a focus on cell death-related candidates. In vivo AD mouse models and in vitro vascular smooth muscle cell (VSMC) systems were employed to investigate the roles of these genes in AD. Potential transcription factors for pyruvate kinase M2 (PKM2) were predicted using the Just Another Simple Array Retrieval/Simple API for Repository (JASPAR) and University of California, Santa Cruz (UCSC) databases, and validated by luciferase reporter and chromatin immunoprecipitation assays. Gain- and loss-of-function approaches were used to dissect the zinc finger protein 460 (ZNF460)–PKM2–gasdermin E (GSDME) axis and the associated impact on pyroptosis and AD progression.
PKM2 expression was markedly elevated in AD tissues. PKM2 silencing suppressed GSDME cleavage, attenuated VSMC pyroptosis, and mitigated experimental AD, whereas PKM2 overexpression aggravated these outcomes. GSDME upregulation rescued pyroptosis in PKM2-depleted cells. Mechanistically, the transcription factor ZNF460 directly bound to the PKM2 promoter, enhancing PKM2 transcription and activating downstream GSDME-mediated pyroptosis. ZNF460 knockdown reduced pyroptotic cell death and preserved aortic wall integrity in vivo.
This study identifies ZNF460 as a novel upstream regulator of PKM2 that drives GSDME-dependent pyroptosis, thereby exacerbating AD progression. Targeting the ZNF460–PKM2–GSDME axis may represent a promising therapeutic strategy for preventing pyroptosis-driven vascular damage in AD.
Transthyretin cardiac amyloidosis (ATTR-CA) results from the extracellular deposition of misfolded transthyretin (mis-TTR) and promotes progressive cardiac dysfunction. Current therapies, such as stabilizers and silencers, reduce further fibril accumulation but fail to clear existing deposits. Monoclonal antibodies (mAbs) targeting mis-TTR have emerged as promising disease-modifying agents, supported by recent observations of circulating anti-TTR antibodies in patients who exhibited spontaneous clinical improvement.
This study aimed to purify natural anti-TTR antibodies from two ATTR-CA patients and compare the respective binding properties to those of a previously described therapeutic anti-TTR mAb fragment (Ab-A F(ab')2). Statistical significance was determined using Student's t-test.
Both natural antibodies and the Ab-A F(ab')2 demonstrated high-affinity binding to misfolded TTR (n = 3), while the competition assays revealed dose-dependent inhibition, indicating shared epitope recognition.
These findings provide translational evidence that therapeutic anti-TTR mAbs may mimic naturally protective antibodies, suggesting that these antibodies could promote amyloid clearance and deliver true disease-modifying benefits in ATTR-CA.
In non-ischemic cardiomyopathy, inflammation is closely associated with cardiac fibrosis, which significantly contributes to adverse outcomes and promotes heart failure (HF). Recent mechanistic studies have demonstrated that interactions between fibrotic and inflammatory pathways create a dynamic, self-perpetuating fibroinflammatory loop, thereby accelerating disease progression. New mono or combination therapies that target this cycle by blocking specific inflammatory signals, modulating the immune response, and altering extracellular matrix (ECM) stiffness may halt or even reverse fibrosis. This opinion article discusses critical recent discoveries, current obstacles, and future opportunities in developing inflammation-focused treatments for cardiac fibrosis in non-ischemic cardiomyopathies.
Rheumatic heart disease (RHD) remains a prevalent cause of valvular heart pathology worldwide, especially in younger populations of low- and middle-income countries. Tricuspid valve (TV) involvement in RHD is usually secondary to left-sided valvular lesions and is often underdiagnosed, since two-dimensional echocardiography (2DE) has limited ability to visualize the complex tricuspid anatomy. Compared with 2DE, three-dimensional echocardiography (3DE) provides an en face visualization of the tricuspid valve, enabling direct planimetric measurements and detailed commissural assessment, and offers advantages for evaluating complex valvular heart disease (VHD). Thus, this study aimed to assess baseline characteristics and valvular morphology in patients with rheumatic tricuspid valve disease using 3DE.
A prospective cohort single-center study conducted between April 2022 and April 2023 included 34 patients with rheumatic TV involvement. Baseline demographics, morphological features, and hemodynamic parameters were assessed using transthoracic 3DE.
The mean age of included patients was 45.5 ± 9.1 years, and 88.2% were female. Most patients had associated left-sided valvular involvement (mitral or combined mitral and aortic). Commissural fusion (50%), leaflet thickening (82.4%), restricted mobility (85.3%), and coaptation loss (58.8%) were predominantly noted. The mean diastolic TV gradient was 3.9 ± 3.4 mmHg, planimetry area 3.3 ± 1.7 cm2, and estimated pulmonary artery systolic pressure 43.3 ± 19.5 mmHg. Mean right ventricular (RV) global longitudinal strain was –23.6 ± 6.1%.
Rheumatic TV involvement is characterized by commissural fusion, leaflet thickening, and coaptation loss, highlighting the diagnostic value of 3DE in identifying morphological patterns that may guide intervention planning.
The sex-specific impact of micronutrient status on heart rate variability (HRV) in adults presenting with palpitations to cardiology outpatient clinics remains unclear. Thus, this study aimed to assess the demographic and biochemical determinants of HRV in a clinical cohort of patients presenting with complaints of palpitations.
This retrospective study included 213 adults aged 18–65 years who presented with palpitations and underwent 24-hour Holter monitoring at our institution between 2023 and 2024. Patients with cardiovascular disease, known arrhythmias, chronic inflammatory conditions, renal dysfunction, or use of medications that affected autonomic function were excluded from the study. Demographic variables, laboratory parameters, and HRV indices were statistically analyzed. The standard deviation of all normal-to-normal intervals (SDNN) was the primary HRV parameter used in both univariate and multivariate linear regression analyses.
The SDNN was significantly lower in women and older adults. In the univariate analyses, age (β = –0.203; p = 0.003), male sex (β = 0.529; p < 0.001), ferritin, serum iron, folate, and Vitamin B12 were all associated with the SDNN. However, in the multivariable model, only male sex (β = 0.467; p < 0.001), iron-binding capacity (IBC) (β = –0.377; p < 0.001), and folate (β = 0.117; p = 0.037) remained independent predictors. Elevated IBC, reflecting functional iron deficiency, was strongly associated with a reduced SDNN, whereas higher folate levels were associated with better autonomic modulation.
In patients presenting with palpitations, the SDNN is influenced by both demographic factors and biochemical markers of iron metabolism. Elevated IBC, reflecting alterations in iron metabolism and iron availability, was associated with impaired autonomic regulation, even in the absence of overt anemia. In contrast, adequate folate status appeared to support a more favorable autonomic function. These findings highlight the importance of integrating iron–vitamin assessment into the evaluation of autonomic function and underscore the need for prospective studies to determine whether correcting these abnormalities can improve HRV and clinical outcomes.