Pulmonary hypertension (PH) is characterized by an abnormally high pressure within the pulmonary arteries, which can be attributed to various factors. Severe diseases affecting pulmonary vessels may result in heart failure and potentially lead to death; these conditions are linked to significant mortality and unfavorable outcomes. Approximately 1% of adults worldwide have PH, and this condition may affect up to 10% of people older than 65 years. Currently, the mechanisms involved in the development of PH are not fully known and are thought to result from multiple coordinated factors. This lack of understanding remains a bottleneck in clinical practice. Numerous studies have confirmed that pulmonary artery endothelial cell (PAEC) dysfunction plays an important role in occlusive pulmonary vascular remodeling and the pathogenesis of PH. Src homology region 2 domain-containing phosphatase-1 (SHP-1) is a regulatory molecule that negatively modulates various cellular mediators and growth factors, primarily playing a negative regulatory role in signal transduction pathways. This review mainly presents an in-depth exploration of the key signaling pathways through which SHP-1 regulates the expression of endothelial cells (ECs), thereby influencing various physiological functions, including proliferation, migration, oxidative stress, angiogenesis, apoptosis, autophagy, the inflammatory response, and vascular permeability. Furthermore, the potential mechanisms through which endothelial SHP-1 plays a role in pulmonary vascular remodeling in PH are discussed. These findings underscore SHP-1 as an encouraging therapeutic target for preventing and managing PH.
Sodium–glucose cotransporter 2 (SGLT2) inhibitors, a novel class of oral antihyperglycemic medications prescribed for type 2 diabetes mellitus, play a beneficial role in slowing the progression of heart failure. However, debate persists regarding the potential link of these inhibitors to acute kidney injury (AKI) in specific clinical conditions.
This study was a retrospective analysis of consecutive patients receiving off-pump coronary artery bypass grafting (OPCABG) at our institution between January 2018 and July 2023. A group of patients who had been administered SGLT2 inhibitors was systematically compared with non-users in a 1:3 ratio using propensity score matching. The principal endpoint was postoperative AKI after OPCABG. In addition, we performed a comprehensive meta-analysis of the associations between SGLT2 inhibitor therapy and AKI risk. The analytical approach combined institutional data with aggregated findings from existing literature.
The analysis encompassed 403 patients who administered SGLT2 inhibitors and 1209 non-users. AKI developed in 54 cases (13.4%) post-OPCABG among individuals who received SGLT2 inhibitors, compared to 373 cases (30.9%) in the control cohort. Statistical analysis demonstrated significantly reduced AKI prevalence in the SGLT2 inhibitor cohort compared to non-users (p < 0.001). The meta-analysis results confirmed a protective association between SGLT2 inhibitor therapy and AKI risk reduction (odds ratio (OR) = 0.525, 95% confidence interval (CI) 0.437–0.631; p < 0.001).
In this study, SGLT2 inhibitor administration was associated with a decreased incidence of postoperative AKI in OPCABG patients.
NCT05888168, https://clinicaltrials.gov/study/NCT05888168?cond=NCT05888168&rank=1.
Transthyretin (TTR) cardiac amyloidosis is a progressive cardiomyopathy with high mortality; however, the role of implantable cardioverter-defibrillators (ICDs) in this population remains unclear.
This retrospective cohort study included patients with confirmed TTR cardiac amyloidosis, with or without ICDs, from January 1, 2001, to December 31, 2024, across all three Mayo Clinic sites (Arizona, Florida, and Minnesota). Diagnosis was confirmed by endomyocardial biopsy or abnormal technetium pyrophosphate (PYP) scintigraphy. A 1:4 propensity score-matched cohort of non-ischemic cardiomyopathy (NICM) patients with ICDs served as a control group. The primary outcome was all-cause mortality, comparing transthyretin cardiac amyloidosis (TTR-CA) patients by ICD status and against matched NICM patients. Secondary analyses evaluated predictors of mortality, including the use of tafamidis and the indication for ICD (primary vs. secondary prevention). Kaplan–Meier and Cox regression analyses were used to assess predictors of survival and mortality.
A total of 463 patients with confirmed TTR cardiac amyloidosis were included. The median follow-up duration was 7.4 years (interquartile range (IQR): 5.3–9.2 years) for the non-ICD group and 6.8 years (IQR: 4.5–9.0 years) for the ICD group. The median age was 74.5 years (IQR: 68.0–80.0 years), and 92.9% of patients were male. Among them, 206 (44.5%) received ICDs and 257 (55.5%) did not. ICD recipients were younger (71.0 vs. 77.0 years; p = 0.001) and had higher rates of hypertension (62.6% vs. 45.6%; p = 0.001), chronic kidney disease (CKD) (62.6% vs. 44.4%; p = 0.001), and diabetes (30.1% vs. 21.8%; p = 0.043). Median left ventricular ejection fraction was lower in the ICD groups (43% vs. 54%; p = 0.007), and N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels were higher in the ICD group (2259.0 pg/mL vs. 1503.0 pg/mL; p = 0.007). Among ICD recipients, 157 (76.2%) received the device for primary prevention, while 48 (23.3%) received the ICD for secondary prevention. Appropriate shocks were delivered in 22 patients (10.6%), primarily for ventricular tachycardia (n = 18) and ventricular fibrillation (n = 4). Inappropriate shocks occurred in six patients (3.0%), and 12 patients (5.8%) experienced device-related complications. Over 10 years of follow-up, ICD implantation did not confer a survival benefit for patients with TTR-CA compared to those without an ICD (p = 0.74). In contrast, a 1:4 propensity-matched NICM cohort with ICDs, which had a median follow-up of 7.1 years (IQR: 4.6–8.8 years), showed significantly improved survival than TTR-CA patients with ICDs (p = 0.034). Among the TTR-CA patients with ICDs, neither the use of tafamidis (p = 0.10) nor the ICD indication (primary vs. secondary prevention; p = 0.85) influenced mortality. In the Cox regression analysis, predictors of mortality in TTR-CA patients included older age (hazard ratio (HR) 1.048; p = 0.001), CKD (HR 1.637; p = 0.029), troponin T >50 ng/L (HR 1.594; p = 0.031), NT-proBNP >3000 pg/mL (HR 1.514; p = 0.050), and ejection fraction <40% (HR 1.935; p = 0.003). ICD implantation was not associated with improved survival (HR 0.932; p = 0.763).
In conclusion, our data suggest that ICD therapy may not provide a significant overall survival benefit in older TTR-CA patients with impaired pump function; thus, prospective studies are warranted before any changes to clinical practice are considered. Key predictors of mortality included reduced ejection fraction and elevated cardiac biomarkers. Additional prospective studies are needed to clarify the role of ICDs in treatment strategies for patients with TTR-CA.
Magnetic resonance imaging (MRI) allows for the assessment of myocardial strain and identification of heart failure (HF) patients with reduced (HFrEF), mildly reduced (HFmrEF), or preserved (HFpEF) left ventricular ejection fraction (LVEF). The cardiovascular angiographic analysis system magnetic resonance (Caas MR) strain (Pie Medical Imaging) has recently been implemented in the IntelliSpace Portal Suite (Philips Healthcare) to assess the global longitudinal strain (GLS), global circumferential strain (GCS), and global radial strain (GRS). However, standard values for this software across different HF entities, as well as normal values, have yet to be established. Thus, this study aimed to establish reference values for the GLS, GCS, and GRS using the Caas MR strain in healthy individuals and HF patients, to assess the ability of these parameters to differentiate between HF subtypes, and to compare CAAS-derived strain values with those obtained using CVI42 software.
Using a 1.5 T Philips Achieva scanner, we analyzed 19 healthy volunteers and 56 HF patients (HFpEF, n = 19; HFmrEF, n = 20; and HFrEF, n = 17) using the feature tracking post-processing software Caas MR Strain. GLS, GCS, and GRS were quantified using 4-chamber-view, 2-chamber-view, and short-axis (SAX) cine images. All volunteers and patients were evaluated by CVI42 to analyze inter-vendor reliability with a validated software.
Mean GLS, GCS, and GRS by Caas MR Strain were significantly different for healthy volunteers compared to HF patients (GLS –15.8 ± 1.9% vs. –11.7 ± 3.0%, p < 0.001; GCS –17.0 ± 2.6% vs. –11.4 ± 3.3%, p < 0.001; GRS 27.3 ± 6.2% vs. 14.5 ± 5.5%, p < 0.001). The upper limit of the 99% confidence interval for healthy volunteers was –14.6% for GLS, –15.3% for GCS and the lower limit of the 99% CI for GRS was 23.1%. GLS, GRS, and GCS by Caas MR Strain were significantly different among HF entities (p < 0.001). Intervendor comparison showed very good agreement for GLS and GRS between Caas MR Strain and CVI42 (GLS r = 0.86, p < 0.001; GCS r = 0.83, p < 0.001; GRS r = 0.76, p < 0.001).
Magnetic resonance imaging assessment of left ventricular myocardial strain using Caas MR Strain software reliably identifies HF patients. Discrimination between the different HF entities is potentially feasible by GLS, GCS, and GRS. Intervendor agreement was most robust for GLS and GCS, but less robust for GRS. For practical clinical use, we propose cut-off values for GLS above –15%, GCS above –15%, and GRS below 23% to define pathological findings.
Cardiac amyloidosis (CA) represents an increasingly recognized but historically underdiagnosed cause of restrictive cardiomyopathy and heart failure. CA is now understood to be more prevalent, particularly in older adults, as advancements in imaging and biomarker technologies have improved detection. The disease results from the misfolding of precursor proteins, primarily immunoglobulin light chains (in light chain (AL) amyloidosis) or transthyretin (in transthyretin (ATTR) amyloidosis), into insoluble fibrils that deposit in myocardial tissue. These deposits cause structural and functional cardiac impairment through both physical infiltration and cytotoxic mechanisms, leading to diastolic dysfunction, arrhythmias, and progressive heart failure. Understanding the molecular basis of amyloid formation and deposition has revealed subtype-specific mechanisms of toxicity and tissue tropism, highlighting the central role of protein instability, proteolytic cleavage, and oxidative stress in disease progression. Furthermore, increasing awareness of phenotypic variability and sex- or ethnicity-based diagnostic disparities has called for earlier recognition and differentiation of CA subtypes. Diagnostic precision is enhanced by a multimodal approach incorporating histopathology, biomarker staging, and advanced imaging techniques such as echocardiography, cardiac magnetic resonance, and nuclear scintigraphy. This review addresses our contemporary understanding of the molecular mechanisms, pathophysiologic cascade, and diagnostic evolution of AL and ATTR CA, emphasizing clinical progress. By delineating the biological mechanisms and tools for early identification, this paper aims to strengthen the framework for diagnosing and managing a disease that was once overlooked but is now at the forefront of modern cardiovascular medicine.
The complex anatomy of coronary bifurcation lesions (CBLs) remains a major challenge in percutaneous coronary interventions (PCIs). Currently, the single-stent strategy offers procedural simplicity; however, this strategy carries a higher risk of side-branch occlusion. Conversely, the two-stent technique improves branch coverage but is associated with increased risks of metal carina formation and late stent thrombosis. This article reviews the technical key points and indications of the provisional stent, T-stent, Crush, and Culotte techniques. Moreover, this article focuses on discussing the core challenges of different methods according to anatomical characteristics, post-dilatation stent morphology, and procedural variability of lesions during PCI. Furthermore, corresponding optimization strategies were explored to guide individualized treatment of CBLs using the Visual Risk Prediction of Side-branch Occlusion in Coronary Bifurcation Intervention (V-RESOLVE) score, functional assessments, and intracoronary imaging combined with the DEFINITION criteria.
Atherosclerosis, a leading cause of global mortality, is a chronic inflammatory disease driven by a vicious cycle of endothelial dysfunction, dysregulated lipid metabolism, and persistent inflammation. This review examines the mechanisms through which diverse triggers initiate the cycle. We discuss key cellular and molecular events, such as the detrimental phenotypic switching of vascular smooth muscle cells. We also describe the processes through which various upstream signals converge on core inflammatory hubs, such as the Toll-like receptor 4 (TLR4)/nuclear factor-κB (NF-κB) pathway and the nucleotide-binding oligomerization domain, leucine-rich repeat-containing family, pyrin domain-containing-3 (NLRP3) inflammasome. By integrating these established mechanisms with recent findings on novel regulators, including the chemokine hemofiltrate CC chemokine 1 (HCC-1) and cell surface glycoRNA, this review identifies several potential new biomarkers. Overall, this review aimed to provide a comprehensive understanding of the pathogenesis of atherosclerosis, informing future research and the development of targeted interventions.
Myocardial infarction with non-obstructive coronary arteries (MINOCA) represents a heterogeneous clinical entity with an unclear pathophysiological basis. Fibrinogen is a key coagulation factor and inflammatory marker that has been associated with atherosclerotic burden in myocardial infarction (MI). However, the role of fibrinogen in MINOCA remains to be established. Therefore, this study aimed to investigate the association between plasma fibrinogen levels and the occurrence of MINOCA, and to evaluate the potential value of fibrinogen assessment in clinical characterization and early identification.
This retrospective study initially screened 1759 patients diagnosed with acute myocardial infarction (AMI) who underwent coronary angiography. A total of 287 patients were analyzed after applying the inclusion and exclusion criteria: 87 with MINOCA and 200 with the MI alongside obstructive coronary artery disease (MI-CAD). A logistic regression analysis was used to assess the association between fibrinogen levels and MINOCA, with subgroup and interaction analyses performed. Receiver operating characteristic (ROC) and restricted cubic spline (RCS) analyses were conducted as supplementary evaluations.
Fibrinogen levels were significantly lower in the MINOCA group compared to the MI-CAD group (p = 0.005). Lower fibrinogen levels were independently associated with increased odds of MINOCA in the multivariate analysis (odds ratio (OR): 0.654, 95% confidence interval (CI): 0.483–0.885; p = 0.006). Quartile analysis revealed a significant inverse trend between fibrinogen levels and risk of MINOCA (p for trend = 0.006), which was further confirmed by a consistent dose–response relationship in the spline analysis (p for overall = 0.035; p for nonlinear = 0.590). The association remained robust across several subgroups. Fibrinogen alone showed a limited discriminative ability (area under the curve (AUC) = 0.605, 95% CI: 0.534–0.675; p = 0.005).
Lower plasma fibrinogen levels were independently associated with the occurrence of MINOCA, suggesting a potential role in its pathophysiology and the early identification of this condition. Fibrinogen alone has limited discriminative utility; however, fibrinogen may contribute to multi-marker approaches for determining and managing MINOCA patients.
Growth differentiation factor-15 (GDF-15) has emerged as a novel biomarker for coronary artery disease (CAD). Although the hypercoagulable state is recognized as a biological mechanism that triggers cardiac events in CAD, the relationship between GDF-15 and coagulation parameters in patients with CAD remains unclear. Thus, this study aimed to investigate the potential relationship between GDF-15 and coagulation parameters in male Chinese patients with CAD.
In total, 892 subjects were enrolled between January 2020 and December 2020, including 592 with CAD and 300 controls. The serum levels of GDF-15, blood cell count, glucose, serum lipids, and coagulation parameters were measured. Kruskal–Wallis or one-way ANOVA with post hoc tests (Holm–Sidak and Dunn's tests), as well as univariate/multivariate linear regression analyses, were used to determine the correlation between GDF-15 and coagulation parameters in male patients with CAD.
Compared to controls, patients with acute myocardial infarction (AMI) and stable angina (SA) showed significantly higher levels of GDF-15 (p < 0.05). Multivariate linear regression revealed that GDF-15 levels were positively associated with activated partial thromboplastin time (APTT) in patients with CAD (β = 0.109, p = 0.024), and inversely associated with antithrombin III (AT3) (β = –0.113, p = 0.028) in an adjusted multivariate regression model. Meanwhile, in a multivariate regression model adjusted for other variables, the GDF-15 levels in patients with SA were inversely associated with AT3 (β = –0.191, p = 0.036). After adjusting for confounders, the GDF-15 levels were positively associated with APTT (β = 0.174, p = 0.002) and inversely associated with monocyte count (β = –0.159, p = 0.025) in patients with AMI.
Elevated levels of GDF-15 in male CAD patients are associated with altered coagulation parameters, suggesting that GDF-15 may serve as a compensatory marker for coagulation parameter instability. These results underscore the potential clinical value of GDF-15 as a novel biomarker for assessing the coagulation status in patients with CAD, especially in the acute coronary syndrome (ACS) subgroup.
Despite the relatively low incidence of Brugada syndrome (BrS) globally, the risk of sudden cardiac death remains alarmingly high, reaching rates of up to 28%. According to current clinical guidelines, implantable cardioverter defibrillators (ICDs) are recommended for high-risk patients. Meanwhile, pharmacological interventions must be used as a backup owing to the limited access to ICDs by eligible patients. Cilostazol, an adenosine uptake inhibitor and phosphodiesterase III inhibitor, has been suggested to reduce the risk of ventricular arrhythmias in BrS patients by stabilizing the action potential dome and lowering the epicardial-to-endocardial repolarization gradient, consequently decreasing the probability of phase II re-entry. However, the effectiveness of cilostazol in this situation has been questioned due to the existence of contradictory results from different case reports. Thus, this literature review aims to synthesize current evidence regarding the potential of cilostazol to lower the risk of ventricular arrhythmias in patients with BrS.
Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is a life-saving intervention for patients with refractory cardiogenic shock or cardiac arrest. However, weaning from VA-ECMO remains challenging and significantly affects patient prognosis. This systematic review examined the multifactorial determinants underlying successful VA-ECMO weaning, highlighting the critical need for integrated evaluation of biventricular function, hemodynamic stability, and microcirculatory perfusion. Key predictive parameters encompass both macrocirculatory indices (including left and right ventricular performance) and metabolic parameters, all of which collectively inform evidence-based weaning decisions. Advanced imaging techniques and multidimensional assessment tools have emerged as promising strategies for optimizing weaning protocols. Pharmacological strategies and precise volume optimization are important for improving weaning success. However, gaps in standardized weaning protocols and bridging therapy algorithms highlight critical, unmet needs. Thus, future efforts should focus on developing dynamic predictive models that incorporate real-time hemodynamic data and on the clinical implementation of microcirculatory assessment technologies.
Sarcoidosis is a rare inflammatory disorder of unknown etiology, characterized by the formation of non-caseating granulomas in affected organs. Additionally, sarcoidosis typically involves multiple systems, with the lungs and thoracic lymph nodes being most commonly affected. While many cases are self-limited and resolve spontaneously, cardiac involvement, although relatively uncommon, can be particularly severe. Indeed, cardiac sarcoidosis may lead to life-threatening arrhythmias, severe heart failure, or sudden cardiac death, significantly impacting prognosis. Meanwhile, the heterogeneity of presentation and disease course can make diagnosis and treatment challenging. An endomyocardial biopsy (EMB) is considered the gold standard for diagnosing cardiac sarcoidosis (CS); despite its high specificity, the sensitivity of this technique is low owing to the often focal and patchy cardiac involvement in sarcoidosis. New imaging techniques, such as fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) and cardiac magnetic resonance (CMR) imaging, can provide valuable information for the accurate diagnosis of CS and can be useful for evaluating treatment response and prognosis. Immunosuppressive treatments, particularly corticosteroids, are considered the cornerstone of therapy for CS. However, randomized clinical trials are lacking, and treatment decisions are based on cohort studies and consensus opinions. Moreover, the optimal strategy for determining when to initiate, how long to continue, and what dosage to use for immunosuppressive therapy remains uncertain.
Complete atrioventricular block (CAVB) following transcatheter aortic valve replacement (TAVR) is primarily attributed to mechanical compression of the penetrating or branching portions of the His bundle, and less commonly, the atrioventricular (AV) node. This study aimed to characterize the electrocardiographic features of stable escape rhythms (ERs) occurring during CAVB after TAVR.
This retrospective study analyzed 12-lead electrocardiograms (ECGs) obtained at three time points: before TAVR (ECG 1), after TAVR but before CAVB (ECG 2), and during CAVB (ECG 3). The ERs on ECG 3 were classified as AV junctional if the rate was 40–60 beats per minute (bpm) and, compared with ECG 2, if the QRS morphology matched in ≥10/12 leads, the QRS duration differed by <10 ms, and the frontal QRS axis differed by <30°. The ERs not meeting these criteria were considered ventricular in origin. Three patients with ERs <40 bpm but matching AV junctional morphology were included in the AV junctional group. ECG 2 was unavailable in 12 patients.
Among the 58 patients included, 56.9% had no conduction abnormalities on baseline ECG 1. Following TAVR (ECG 2), left and right bundle branch blocks were observed in 69.6% and 17.4% of the patients, respectively. During CAVB (ECG 3), the ERs were presumed to originate from the AV junction in 23 patients (39.6%), from the ventricles in 28 (48.3%), and had an undetermined origin in 7 (12.1%).
Consistent with the anatomical regions commonly affected by the prosthetic aortic valve during TAVR, a substantial proportion of patients exhibited ERs likely originating from the AV junction, suggesting a potential role for conduction system pacing in managing CAVB in this setting of patients.
Emerging evidence has implicated the gut microbiota in the pathogenesis and progression of numerous cardiovascular diseases. Atherosclerosis is a major pathological process that leads to many severe cardiovascular complications. Meanwhile, atherosclerosis patients may experience local and systemic inflammatory responses, with structural changes in the intestinal microbiota and increased mucosal permeability. Currently, the role of gut microbiota-derived metabolites in atherosclerosis pathology is of great concern. Relevant findings have highlighted the potential direct or indirect impacts of gut microbiota on the metabolic health of the host via the production of various metabolites. Thus, this review places an emphasis on bile acids (BAs), metabolites derived from and regulated by the gut microbiota. BAs can delay the pathological processes associated with atherosclerosis, underscoring the significance of these metabolites as an early marker for disease progression risk. In addition, we explore the potential of BA-related gut metabolites as novel therapeutic targets for atherosclerosis, and propose several promising directions for future research.
Metabolic dysfunction significantly influences cardiovascular outcomes following ST-elevation myocardial infarction (STEMI). The triglyceride–glucose (TyG) index and triglyceride–glucose–body mass index (TyG–BMI) serve as surrogate markers of insulin resistance, whereas B-type natriuretic peptide (BNP) levels reflect cardiac dysfunction. However, the combined prognostic value of these biomarkers for predicting major adverse cardiovascular events (MACEs) in patients with STEMI remains underexplored.
We conducted a retrospective cohort study of 1177 consecutive patients with STEMI who underwent percutaneous coronary intervention between August 2018 and December 2023. Patients were stratified into four groups based on the TyG index (cutoff: 7.2), TyG–BMI (cutoff: 186), and BNP level (cutoff: 300 pg/mL). The primary endpoint was MACEs, defined as a composite of all-cause mortality, nonfatal myocardial infarction, ischemia-driven repeat revascularization, heart failure hospitalization, and cerebrovascular events. Cox proportional hazards models with progressive adjustment were employed to assess independent and combined prognostic significance.
A total of 483 patients (41.0%) experienced MACEs during a median follow-up of 461 days (interquartile range (IQR): 79–672). Patients with both an elevated TyG index (≥7.2) and a high BNP concentration (≥300 pg/mL) demonstrated the highest cardiovascular risk profile and a more than twofold increased MACE risk (hazard ratio (HR) 2.18, 95% confidence interval (CI): 1.57–3.03; p < 0.001) compared with the reference group (those with a low TyG index and low BNP concentration). Similarly, patients with elevated TyG–BMIs (≥186) and BNP levels had an 81% increased risk (HR 1.81, 95% CI: 1.30–2.51; p < 0.001). Meanwhile, the combined TyG index + BNP model demonstrated superior predictive accuracy (area under the curve (AUC): 0.67) compared with the individual biomarkers and the established Global Registry of Acute Coronary Events (GRACE) score (AUC: 0.58). Subgroup analyses revealed particularly pronounced associations in older patients, females, and those with hypertension.
The combination of the TyG index or TyG–BMI with BNP provides enhanced prognostic stratification for predicting MACEs in STEMI patients, offering superior discriminatory capacity compared with that of individual biomarkers. This integrated approach may facilitate personalized risk assessment and guide therapeutic decision-making in clinical practice.
Myocardial fibrosis represents the initial stage of cardiac failure and is characterized by the accumulation of extracellular matrix proteins. The fibrogenic niche provides a unique microenvironment for myocardial fibrosis and consists primarily of extracellular matrix proteins, various types of cardiac resident cells, inflammatory cells, extracellular vesicles, and soluble factors. Meanwhile, the composition and contents of this microenvironment undergo dynamic changes during the repair of damaged tissues. Several studies have demonstrated that the fibrogenic niche plays a key role in the activation of fibroblasts, the development of inflammation, and the onset of microvascular dysfunction. Studying the fibrogenic niche has emerged as a new method to clarify the mechanisms involved in myocardial fibrosis, and can potentially facilitate the early diagnosis and individualized medical treatment for the disease.
Inflammation has recently been identified as a critical regulator of the pathophysiology and prognosis of acute coronary syndrome (ACS). The systemic immune–inflammation index (SII), derived from platelet, neutrophil, and lymphocyte counts, has gained attention as a potential marker for predicting adverse outcomes in cardiovascular diseases. However, the prognostic value of the SII, particularly in relation to gender differences, has not been extensively studied.
Thus, we conducted a retrospective cohort study of 835 patients hospitalized for ACS at Hippokration Hospital, Thessaloniki, Greece, between 2017 and 2023. The SII was calculated using blood samples taken at admission. Logistic and Cox regression models were used to evaluate the relationship between the SII and all-cause mortality, with stratified analyses conducted according to gender. Receiver operating characteristic (ROC) analysis, Kaplan–Meier survival curves, and restricted cubic spline (RCS) modeling were also performed to assess the discriminative ability and non-linear associations of the SII with mortality.
A total of 835 patients were included, with a median follow-up of 25 months. An elevated SII was independently associated with increased long-term mortality, with patients in the highest SII quartile exhibiting a 2.3-fold higher risk of death compared to those in the lowest quartile (adjusted hazard ratio (aHR) = 2.31, 95% confidence interval (CI): 1.60–3.32; p < 0.001). The optimal cut-off value for the SII was identified as 1864.19. Gender-stratified analyses revealed a stronger prognostic value in women compared to men (area under the curve (AUC) = 0.70 vs 0.58; p = 0.018). The Kaplan–Meier and Cox regression analyses confirmed significantly worse survival for patients with SII levels above this threshold (p < 0.05). The RCS modeling demonstrated a non-linear relationship between the SII and mortality, with a marked increase in risk at higher levels of the SII, especially in women.
The SII is a simple, easily accessible biomarker that independently predicts mortality in ACS patients, with notable gender-specific differences in the prognostic value of the SII. Nonetheless, incorporating SII into routine risk assessment could enhance risk stratification and improve personalized treatment strategies, particularly in settings with limited resources.
Surgical repair of partial and transitional atrioventricular septal defects (AVSDs) aims to achieve optimal outcomes with minimal need for reintervention. This study aimed to evaluate the mid-term outcomes of AVSD repair in both pediatric and adult populations.
We retrospectively reviewed all patients who underwent surgical repair for partial or transitional AVSDs at our center between January 2019 and December 2022. Key outcomes, including mortality, reoperation, and atrioventricular valve (AVV) repair strategies, were assessed during follow-up.
A total of 136 patients were included (partial AVSD, n = 100; transitional AVSD, n = 36), with a median follow-up of 50.5 months. The median hospital stay was 14 days. No early or late deaths occurred. Reoperation was required in four patients (2.9%); all reoperations included left atrioventricular valve (LAVV) reoperation. However, reoperation rates did not differ significantly between AVSD subtypes (p = 1.000) or age groups (p = 0.177). The incidence of moderate or greater LAVV regurgitation showed no significant difference between patients with and without ring annuloplasty, either postoperatively or at the final follow-up (both p = 1.000).
Surgical repair of partial and transitional AVSDs results in excellent mid-term survival and a low reoperation rate across both pediatric and adult patients. Continued refinement of AVV repair strategies remains essential to reduce the risk of LAVV reintervention and prevent left ventricular outflow tract obstruction. Long-term follow-up is warranted to improve the evaluation of the durability of techniques such as suture annuloplasty and ring annuloplasty.
Atherosclerosis, a lipid-driven chronic inflammatory disease, is the primary pathological basis of cardiovascular diseases, characterized by endothelial injury, lipid deposition, immune cell infiltration, and chronic inflammation. The NOD-like Receptor Pyrin Domain-Containing 3 (NLRP3) inflammasome has emerged as a crucial mediator of inflammation in atherosclerosis, with caspase recruitment domain family member 8 (CARD8) acting as a key regulatory component. Indeed, CARD8, a member of the caspase recruitment domain family, regulates immune responses by modulating inflammasome activity, particularly NLRP3. Recent studies suggest that CARD8 influences various aspects of atherosclerotic development, including lipid accumulation, oxidative stress, vascular inflammation, smooth muscle cell proliferation, and plaque instability. Thus, this review summarizes the latest findings on the role of CARD8 in the pathogenesis of atherosclerosis, with a focus on the regulatory effects of this component on immune cells and inflammatory pathways. We also discuss the potential of targeting CARD8 as a therapeutic strategy for atherosclerosis, exploring the current preclinical and clinical evidence.
Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), originally developed for glycemic control in type 2 diabetes, have emerged as transformative agents with broad therapeutic applications across multiple organ systems. This review explores the expanding role of GLP-1 RAs in managing cardiometabolic diseases, including obesity, heart failure (particularly with preserved ejection fraction), chronic kidney disease (CKD), and metabolic dysfunction-associated steatotic liver disease (MASLD). Robust clinical trial data support the efficacy of GLP-1 RAs in promoting weight loss, improving cardiovascular outcomes, and preserving renal function, with additional trials underway to further strengthen and expand the evidence base. Despite the growing utility of GLP-1 RAs, challenges related to cost, access, adherence, and implementation persist, particularly for indications beyond diabetes. However, innovations such as oral formulations and combination therapies may help improve accessibility and sustained use. As clinical guidelines evolve, targeted integration of GLP-1 RAs into care models may transform the prevention and treatment landscape for complex, chronic diseases.
With ongoing technological advancements and device innovations, transcatheter aortic valve replacement (TAVR) has become a well-established therapeutic approach for managing aortic stenosis and regurgitation. As indications for TAVR expand, particularly into younger patient populations, the incidence of TAVR-associated infective endocarditis (TAVR-IE) has concurrently increased. Although the reported incidence of TAVR-IE remains relatively low (0.3%–2.0% per 100 patient-years), its clinical outcomes are notably poor, with mortality rates considerably higher than those observed in general infective endocarditis (IE). Moreover, the microbiological profile of TAVR-IE differs distinctly from surgical aortic valve replacement-associated IE (SAVR-IE), predominantly involving Enterococcus spp., Staphylococcus aureus, and coagulase-negative staphylococci. This review systematically summarizes the epidemiology, diagnosis, microbial etiology, prevention strategies, clinical prognosis, and management approaches for TAVR-IE, providing clinical insights and identifying key areas for future research.
Tricuspid regurgitation (TR) is a critical factor in the progression of right heart failure. Although conventional open surgery remains the definitive treatment, the application of this technique is significantly limited in older and high-risk patients due to frequent comorbidities, including impaired right ventricular functional reserve, pulmonary hypertension, and multi-organ dysfunction, which lead to substantially increased surgical risks. Transcatheter tricuspid valve intervention (TTVI), which achieves anatomical correction through minimally invasive approaches, has emerged as an effective alternative strategy for patients deemed ineligible for surgery. During these procedures, anesthesiologists face three core challenges: susceptibility to acute changes in the preload of the right ventricle, a high risk of circulatory collapse (particularly in functional TR with right ventricular decompensation), and the precise integration of intraoperative transesophageal echocardiography (TEE) with hemodynamic monitoring. Consequently, anesthesiologists who become experts in the pathological staging of TR, key points of image-guided device implantation, and warning indicators of circulatory collapse can help maintain perioperative stability. Moreover, gaining a thorough understanding of the pathological progression of tricuspid valve disease, improving the assessment of right heart function, and optimizing the TTVI process and management capabilities are crucial for improving patient outcomes. Thus, establishing a perioperative anesthetic strategy focused on right heart protection may reduce cardiovascular-related complications and all-cause mortality.
Recent advancements have introduced novel cardiac myosin inhibitors (CMIs) that have demonstrated significant efficacy in treating hypertrophic cardiomyopathy (HCM). This meta-analysis aimed to clarify the current understanding of the impact of CMIs on echocardiographic cardiac structure and function in patients with HCM.
A comprehensive search of the PubMed, Cochrane Library, and Embase databases was conducted from inception until September 14, 2025. The studies reporting the impact of CMIs on echocardiographic cardiac structure and function in HCM patients were included.
Ultimately, this meta-analysis included 10 studies: five randomized controlled trials (RCTs), three echocardiographic sub-studies derived from RCTs, and two long-term cohort studies. A total of 938 patients were enrolled in these studies. This meta-analysis revealed that CMIs significantly reduce interventricular septum thickness (mean difference (MD): –1.77, 95% confidence interval (CI): –3.30 to –0.23; p = 0.0240). CMIs were also shown to significantly reduce left ventricular mass index (MD: –18.15, 95% CI: –32.65 to –3.65; p = 0.0141). Moreover, the pooled results demonstrated that administering CMIs can significantly reduce left ventricular ejection fraction (MD: –3.22, 95% CI: –5.60 to –0.85; p = 0.0078). CMIs also significantly improved echocardiographic parameters of left ventricular diastolic function, such as the left atrial volume index (MD: –5.75, 95% CI: –7.87 to –3.64; p < 0.0001) and septal E/e′ ratio (MD: –3.80, 95% CI: –4.74 to –2.87; p < 0.0001). However, the results did not reveal an association between CMIs and the risk of atrial arrhythmias (risk ratio (RR): 0.98, 95% CI: 0.33 to 2.94; p = 0.9689).
CMIs have shown great efficacy in improving left ventricular structure and diastolic function in HCM patients. Additionally, CMIs can reduce left ventricular ejection fraction. However, the impact of CMIs on the risk of atrial arrhythmias remains unclear.
CRD420251243904, https://www.crd.york.ac.uk/PROSPERO/view/CRD420251243904.
Coronary artery calcium (CAC) reflects the overall atherosclerotic burden. The CAC density is inversely associated with plaque vulnerability. Intravascular ultrasound (IVUS)-defined attenuated plaques represent unstable lesions, which are linked to adverse clinical outcomes. Meanwhile, the determination as to whether coronary computed tomography angiography (CCTA)-derived CAC metrics can serve as noninvasive markers of attenuated plaques remains uncertain.
This retrospective study included coronary artery disease (CAD) patients who underwent both CCTA and IVUS between January 2023 and December 2024 at our medical center. CCTA was used to quantify plaque volume, density, and composition (lipid, fiber, and calcium), while IVUS was employed to characterize the plaques as attenuated and non-attenuated.
Among 94 patients with 150 coronary plaques, calcium volume showed a very strong correlation with total plaque volume (rs = 0.953, p < 0.0001). Meanwhile, attenuated plaques exhibited significantly lower calcium density (321.00 vs. 499.00 Hounsfield units (HU); p = 0.0004), calcium volume (55.20 vs. 168.10 mm3; p = 0.003), and calcium percentage (33.30% vs. 55.40%; p = 0.015) compared with the non-attenuated plaques. Multivariate logistic regression analysis identified lower CAC density as the only independent predictor of IVUS-confirmed attenuated plaques (odds ratio = 0.994, 95% confidence interval (CI): 0.990–0.997; p = 0.0002). The area under the receiver operating characteristic (AUROC) curve for CAC density in diagnosing attenuated plaques was 0.735 (95% CI: 0.603–0.868; p = 0.0004). At a cutoff of 461.50 HU, the sensitivity and specificity were 81.8% and 66.1%, respectively.
CCTA-derived CAC volume reflects the atherosclerosis (AS) burden, while lower CAC density independently predicts IVUS-confirmed attenuated plaques. A higher CAC density was associated with plaque stability, suggesting that the CCTA-derived CAC density may serve as a noninvasive marker of plaque stability, aiding in the assessment of plaque vulnerability and risk stratification.
Rheumatic heart disease (RHD) is a global autoimmune disease that contributes significantly to cardiovascular mortality. However, a comprehensive investigation into age-specific mortality patterns across diverse regions remains limited. To address this issue, this study aimed to investigate alterations in RHD mortality and disease burden measured by disability-adjusted life years (DALY), and modifiable risk factors across 204 countries and regions during the preceding three decades. Additionally, this study endeavored to forecast the trends for RHD in the coming decade and to explore the associations with the age, period, and birth cohort by analyzing data from the Global Burden of Disease (GBD) 2019.
We present up-to-date mortality and DALY data for RHD sourced from the GBD 2019 data. We employed the age–period–cohort (APC) model to assess local and net drift, as well as the influences of age, period, and birth cohort. Additionally, we examine modifiable risk factors and provide projections for RHD mortality trends in the coming decade.
Age-standardized mortality rates for RHD exhibited a net drift ranging from –5.59 (95% confidence interval (CI): –5.84 to –5.34) in high–middle sociodemographic index (SDI) regions, to –2.34 (95% CI: –2.42 to –2.25) in low SDI regions. Comparable trends were observed with DALY. High systolic blood pressure was the major metabolic risk factor in both 1990 and 2019. Projections indicate a global reduction in RHD mortality rates over the coming decade. Nevertheless, individuals in low-SDI regions are projected to bear a substantial mortality burden in both 2019 and 2029, accentuating a widening sex disparity.
In summary, this study found that age, period, and birth cohort effects for RHD were positive globally, except for low SDI regions. The widening health disparities between regions indicate an imminent threat of significant disease burden. Thus, this study underscores the imperative requirement for targeted interventions, enhanced healthcare accessibility, and sex-sensitive strategies to alleviate the burden of death and disability associated with RHD, particularly in low SDI regions.
This study aimed to evaluate the clinical efficacy of in-line mechanical insufflation–exsufflation (IL-MIE) in airway secretion management in patients receiving invasive mechanical ventilation after cardiopulmonary bypass (CPB).
A total of 56 patients who underwent CPB and required invasive mechanical ventilation in the Cardiac Surgery Intensive Care Unit of Beijing Anzhen Hospital, Capital Medical University, between July 2015 and July 2020, were enrolled and divided into an IL-MIE group (n = 28) and a conventional suction (CS) group (n = 28). The IL-MIE group received automated secretion clearance every 30 min for 8 h, supplemented with CS as needed, whereas the CS group received standard CS treatment. General patient data, respiratory and hemodynamic parameters, ventilator settings, CS frequency, mechanical ventilation duration, and intensive care unit (ICU) length of stay were recorded during the 8 h intervention.
At 4 h and 8 h, the IL-MIE group exhibited significantly higher arterial oxygen partial pressure, oxygenation index, and static compliance and low plateau pressure (p < 0.05). Heart rate was significantly lower in the IL-MIE group at 4 h ((99.21 ± 13.87) vs. (89.32 ± 10.66); p < 0.01) and 8 h ((96.71 ± 14.47) vs. (89.61 ± 9.34); p = 0.033). The IL-MIE group required fewer CS interventions (0 (0, 1) vs. 4 (3, 4); p < 0.01) and had a shorter duration of mechanical ventilation (20 (16.75, 22) vs. 24 (18.75, 26.5); p = 0.029) than those in the CS group.
By mimicking physiological airway clearance, IL-MIE significantly improves oxygenation and lung compliance, reduces the duration of mechanical ventilation, and maintains hemodynamic stability during respiratory management in patients after CPB.
Resistant hypertension (RH) is a high-risk phenotype characterized by blood pressure readings ≥130/80 mmHg despite maximally tolerated therapy with three antihypertensive agents, including a diuretic, or controlled blood pressure requiring four or more medications. The diagnosis of RH requires a structured evaluation that confirms accurate blood pressure measurement, excludes pseudoresistance—particularly nonadherence and white coat hypertension—and identifies secondary causes such as obstructive sleep apnea, primary aldosteronism, renovascular disease, pheochromocytoma, and Cushing syndrome. RH arises from overlapping mechanisms, including activation of the renin–angiotensin–aldosterone system (RAAS), sympathetic overactivity, arterial stiffness, volume expansion, and immune-mediated pathways. Management begins with lifestyle modification and optimized triple therapy, followed by mineralocorticoid receptor antagonists as the preferred fourth-line treatment. Emerging pharmacological options, such as sodium–glucose cotransporter-2 (SGLT2) inhibitors, glucagon-like peptide-1 (GLP-1) receptor agonists, endothelin receptor antagonists, aldosterone synthase inhibitors, and angiotensin receptor and neprilysin inhibitors (ARNIs), offer additional therapeutic potential; meanwhile, device-based interventions, including renal denervation and baroreflex activation therapy, have shown sustained blood pressure reductions in selected patients. Future directions highlight precision medicine, digital health technologies, and artificial intelligence as methods to improve diagnosis, guide individualized therapy, and enhance long-term blood pressure control.
Diabetic cardiac autonomic neuropathy (DCAN) is a common and serious complication of diabetes, and its early diagnosis and treatment are important for preventing cardiovascular events. At present, its diagnosis is mainly based on multiple functional investigations, such as heart rate variability (HRV) and cardiovascular reflex test. However, these methods are cumbersome to perform, time-consuming, and readily affected by patient cooperation and operator technique, resulting in limited clinical application. More importantly, DCAN still lacks standardized early diagnostic criteria and specific biomarkers. In recent years, the integration of multi-index diagnosis such as HRV, electrocardiograms (ECGs), continuous glucose monitoring (CGM) and machine-learning algorithms has improved the accuracy of early screening and prognosis. Here, we systematically review the latest research progress in relation to the pathological mechanism, diagnosis and treatment of DCAN, with a focus on novel biomarkers, therapeutic targets, and the potential for individualized treatment. This review provides new insights into DCAN, as well as the basis for early diagnosis and precise intervention.
Heart failure with preserved ejection fraction (HFpEF) has progressively emerged as the predominant form of heart failure. Thus, studies on the underlying mechanisms of HFpEF have shifted from pathophysiological to molecular factors. Meanwhile, previous studies have primarily focused on inflammation, oxidative stress, metabolic dysregulation, and impaired cardiac compliance (manifesting as ventricular hypertrophy and interstitial fibrosis). In addition to conventional guideline-directed medical therapies, novel therapeutic strategies targeting these aforementioned pathogenic pathways have been investigated. This review aimed to summarize recent progress in HFpEF pathogenesis and emerging treatment approaches, offering insights for developing novel diagnostic and management strategies.
Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have been shown to reduce major adverse cardiovascular events (MACEs) in patients with type 2 diabetes mellitus (T2DM) and high cardiovascular risk. However, the efficacy of GLP-1 RAs on the outcomes of MACEs across different racial and sex groups among patients with and without T2DM remains underexplored. Thus, this study aimed to evaluate the association between GLP-1 RAs and MACEs in patients with and without T2DM based on race and sex.
We conducted a systematic literature search on the PubMed and Scopus databases, as well as ClinicalTrials.gov, for relevant randomized controlled trials (RCTs) from inception to July 5, 2025. Trials were eligible for inclusion if the included adults (≥18 years) had been randomized to a GLP-1 RA versus placebo group, and MACEs were reported as an outcome. Trials combining GLP-1 RAs with other investigational glucose-lowering agents were excluded. Risk ratios (RRs) and 95% confidence intervals (CIs) were pooled using a random-effect model, and a p-value of <0.05 was considered statistically significant.
Nine RCTs involving 81,266 patients were included in the analysis. The mean age of patients was 65 years. Compared with the placebo, GLP-1 RAs significantly reduced the risk of MACEs in males (RR, 0.82; 95% CI: 0.77–0.86; p < 0.001) and females (RR, 0.81; 95% CI: 0.75–0.88; p < 0.001). Meanwhile, across racial groups, GLP-1 RAs significantly reduced the risk of MACEs in Caucasian patients (RR, 0.87; 95% CI: 0.79–0.96; p < 0.001) compared with placebo. However, no significant difference was observed for the risk of MACEs in Black patients (RR, 1.05; 95% CI: 0.72–1.53; p = 0.80) when comparing GLP-1 RAs with placebo.
This meta-analysis demonstrates that GLP-1 RAs significantly reduce the risk of MACEs in both males and females, as well as across various racial groups in patients with or without T2DM. However, the lack of significant benefit in Black patients suggests potential racial disparities in the enrollment and efficacy of GLP-1 RAs for cardiovascular outcomes.
Heart failure (HF) remains a global health challenge characterised by significant clinical heterogeneity, necessitating more precise tools for diagnosis and risk stratification. Olink proteomics, a high-throughput platform based on proximity extension assays (PEAs), has emerged as a powerful technology for exploring the molecular landscape of HF. Despite a growing number of studies utilising this platform, a comprehensive synthesis of its clinical and mechanistic contributions is still lacking. This review systematically examines the application of Olink proteomics across the HF continuum. We synthesised evidence regarding its role in biomarker discovery for early detection and prognosis, its ability to dissect key pathophysiological pathways such as inflammation and fibrosis, and its emerging potential to guide precision medicine. By critically evaluating technological advances, current challenges, and future directions, this review concludes that Olink proteomics is pivotal for transitioning HF management from a phenotype-driven to a mechanism-based paradigm, paving the way for targeted therapies and improved patient outcomes.
Heart failure (HF) represents a class of cardiovascular diseases that poses a serious threat to global health. Although current pharmacological and device-based therapies have exhibited some progress, significant challenges remain, including suboptimal treatment responses and the inability to effectively halt disease progression. Extracellular vesicles (EVs) are nanoscale membranous particles actively secreted by cells, which are capable of transporting bioactive molecules such as nucleic acids and proteins to mediate intercellular communication. Owing to the broad cellular origins and excellent biocompatibility of EVs, these particles offer extensive therapeutic potential. This review systematically elaborates on the key aspects of EVs, including the core molecular composition of these particles, as well as the biogenesis pathways and functional regulatory mechanisms involved. We further dissect the functional heterogeneity of EVs derived from cardiomyocytes, cardiac fibroblasts, endothelial cells, and immune cells in HF, highlighting the dual roles of EVs in either promoting or counteracting disease progression via cargo-dependent mechanisms. Additionally, we explore the translational applications of EVs in the diagnosis and treatment of HF, covering EV isolation, characterization, and scalable production strategies. The potential use of EVs as biomarkers, as well as the precision engineering of EVs for targeted clinical therapy, are also critically discussed.
Cardiovascular diseases (CVDs) represent the primary cause of death worldwide, thereby demanding effective preventive measures. Incidental physical activity (IPA), which encompasses non-exercise movements naturally integrated into daily routines, offers a practical and promising strategy for reducing CVD risk. Research, particularly from the UK Biobank, has consistently highlighted the cardiovascular advantages of IPA across diverse populations. However, systematic guidelines for integrating IPA into cardiovascular care are limited. Thus, this review aims to provide a comprehensive synthesis of IPA, including a definition, classification by intensity, current evidence linking IPA to cardiovascular health, and the underlying mechanisms involved. Present research underscores the extensive benefits of IPA, particularly the pronounced effectiveness of vigorous IPA (VIPA). However, approaching these findings with caution is essential, especially considering the limited representation of individuals predisposed to exercise-induced sudden cardiac events in middle-aged and older cohorts. Therefore, while the advantages of IPA are clear, further investigation is warranted to understand the implications of IPA for all populations. In conclusion, we recommend integrating IPA as a complementary strategy alongside structured exercise in clinical practice. However, emphasizing risk mitigation strategies for VIPA is crucial, particularly for at-risk individuals. This review aims to provide practical guidance on the effective implementation of IPA in cardiovascular health management.
Gut microbiota are associated with heart failure (HF); however, the causal relationship between gut microbial communities and HF of varying etiologies remains incompletely established.
This study leveraged two-sample Mendelian randomization (MR) to investigate whether genetically determined gut microbiota features causally influence HF and its related subtypes. Instrumental variables (IVs) for gut microbiota were derived from a large-scale, genome-wide association study (GWAS) of microbial traits conducted by the MiBioGen consortium, which included 18,340 individuals. Summary statistics for HF and its subtypes were extracted from the FinnGen Release 7, encompassing 19,350 all-cause HF cases and 288,996 controls. The Wald ratio and inverse-variance weighted analyses were applied to calculate the causal estimates.
A total of 19 single-nucleotide polymorphisms (SNPs) corresponding to 18 gut microbial taxa were selected as IVs. A significant inverse causal association was identified between the family Peptostreptococcaceae and the risk of hypertensive heart disease (odds ratio (OR): 0.355, 95% confidence interval (CI): 0.193–0.656; p < 0.001; q = 0.018). Several additional taxa showed suggestive causal associations with HF or its precursor conditions, although these did not survive multiple-testing correction.
Genetically predicted enrichment of Peptostreptococcaceae is causally associated with a lower risk of hypertensive heart disease. These MR findings warrant a mechanistic dissection of Peptostreptococcaceae-mediated pathways as a potential therapeutic lever for the prevention and treatment of hypertension-mediated HF.
Transcatheter aortic valve implantation (TAVI) has evolved from an experimental, last-resort procedure in 2002 to a first-line therapy for aortic stenosis; moreover, the 2025 ESC/EACTS (European Society of Cardiology/European Association for Cardiothoracic Surgeons) guidelines marked a paradigm shift beyond traditional risk stratification toward earlier intervention and broader patient selection. Current evidence demonstrates the non-inferiority or superiority of TAVI to surgical aortic valve replacement across all risk categories, with the guidelines now recommending TAVI for patients aged ≥70 years and formally endorsing early intervention in asymptomatic severe stenosis when procedural risk is low. Meanwhile, critical challenges persist despite large-scale systematic reviews demonstrating significant mortality reduction following TAVI, including paravalvular leak rates of 10–25% compared to near-zero rates with surgery, and subclinical leaflet thrombosis affecting up to 30% of patients with unclear optimal management strategies. Moreover, the expansion toward younger populations exposes critical knowledge gaps, including unknown long-term durability beyond 10 years, structural valve degeneration rates of 4.8–13.3% at 5–7 years, and complex reintervention scenarios with reported mortality rates of 17.1% for surgical TAVI explantation. Thus, this review synthesizes contemporary evidence within the framework of the 2025 guidelines while examining unique aspects, including the pathophysiology of subclinical leaflet thrombosis, polymeric heart valve technologies as next-generation solutions, and the critical durability questions that will determine the role of TAVI in younger patients. Next-generation polymeric valves utilizing materials such as polyhedral oligomeric silsesquioxanes-polycarbonate urethane (POSS-PCU), poly(styrene-b-isobutylene-b-styrene) (SIBS), and siloxane polyurethane-urea have shown promising preclinical results in terms of enhanced durability and reduced thrombogenicity, although comprehensive clinical validation remains necessary. As TAVI practice evolves under new guideline recommendations emphasizing early intervention and simplified antithrombotic management, this thorough analysis can provide essential context for understanding both current capabilities and future directions in transcatheter valve therapy.
Four-dimensional (4D) flow cardiac magnetic resonance (CMR) is an advanced imaging modality that enables comprehensive qualitative and quantitative assessment of blood flow in the three spatial dimensions plus time. This technique is more accurate, reproducible, and easier to interpret visually than conventional two-dimensional phase-contrast techniques. In this narrative review, we synthesize our clinical experience—including practical insights from representative cases from routine practice—with published research to describe the technical foundations, clinical applications, advantages, and limitations of this technique. We discuss the technical aspects, including spatial and temporal resolution, velocity encoding, contrast administration, workflow requirements, and post-processing software, and their influence on diagnostic performance. Thus, 4D-flow CMR imaging can accurately assess cardiac shunts through advanced visualization of pathlines and streamlines, providing direct quantification of pulmonary flow: systemic flow ratios, blood flow volumes, and complex hemodynamic patterns in congenital heart disease (CHD). Moreover, 4D-flow CMR imaging provides robust characterization of valvular and aortic disease through dynamic flow analysis and quantitative hemodynamic metrics. Overall, 4D flow CMR imaging is a powerful, noninvasive diagnostic tool that can greatly enhance clinical decision-making. The growing body of evidence supports the use of 4D-flow CMR imaging in routine clinical practice, particularly for evaluating CHD and valvular and aortic disorders.
Various anatomical factors have been related to mortality after endovascular aortic aneurysm repair (EVAR). This systematic review investigated the impact of the pre-operative maximum aortic aneurysm diameter on mortality after standard and complex EVAR.
The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines were followed to search the MEDLINE, EMBASE, via Ovid and CENTRAL databases, until 31st July 2025. Randomized controlled trials and observational studies were eligible if they were published between 2015 and 2025 and reported on the association of the pre-operative maximum aortic aneurysm diameter with a 30-day and midterm mortality follow-up in standard and complex EVAR patients. The Newcastle-Ottawa Scale assessed the risk of bias. The primary outcome was the impact of the pre-operative maximum aortic aneurysm diameter on 30-day mortality after standard and complex EVAR.
From 1182 studies, 25 were included; 19 reporting on standard (130,476) patients and six on complex EVAR (14,097) patients. A significant heterogeneity in terms of maximum pre-operative aortic aneurysm diameter threshold to identify larger aneurysms was detected. Regarding standard EVAR, eight studies evaluated the impact of the pre-operative maximum abdominal aortic aneurysm (AAA) diameter on 30-day mortality (smaller: 0.3–13.2% vs. larger: 0.7–20.8%) with conflicting outcomes. Four studies (4/8 studies; 50%) concluded that a larger diameter was related to higher 30-day mortality in patients with standard EVAR, while four showed no statistical significance. Two out of five standard EVAR studies that investigated the pre-operative AAA diameter as an independent predictor for 30-day mortality confirmed this finding. During the mid-term follow-up, ten studies showed that the pre-operative maximum AAA diameter was independently related to mortality after standard EVAR. In complex EVAR, four out of six studies showed that the 30-day mortality was higher (smaller: 0.5–7.0% vs. larger: 4.0–15.0%) in larger aortic aneurysms, including juxta-, para-, supra-renal, and thoracoabdominal aortic aneurysms. Four out of five (80.0%) studies showed that a larger diameter was an independent predictor for follow-up mortality after complex EVAR.
The pre-operative aortic aneurysm diameter seems to be related to mortality after standard or complex EVAR. However, the impact of the pre-operative aortic aneurysm diameter on mortality seems to be more prominent in complex EVAR cases, with 80% of studies confirming this finding.
Hypertrophic cardiomyopathy (HCM) represents the most common inherited cardiac disease and a leading cause of heart failure, arrhythmias, and sudden cardiac death in young individuals. For decades, management of HCM has relied on symptom control with β-blockers, calcium channel blockers, disopyramide, or invasive septal reduction in advanced cases. The identification of pathogenic sarcomere variants and the recognition of hypercontractility as a central disease mechanism have paved the way for cardiac myosin inhibitors (CMIs), the first truly disease-specific pharmacological therapy for HCM. Indeed, CMIs represent a revolutionary therapeutic paradigm that redefines the standard of care by translating molecular discovery into clinical application. This review provides a guide to the mechanistic basis of sarcomere modulation, summarizes the clinical evidence for mavacamten and aficamten, and critically evaluates the evolving roles of both medications in obstructive and non-obstructive HCM.