Search Results (1,359)

Background and Objectives: Breast cancer surgery is increasingly performed in older patients with multimorbidity, in whom cardiovascular disease and frailty may substantially modify perioperative risk, including vulnerability to heart failure decompensation and other major medical complications. However, most available studies report global perioperative complication rates and composite medical endpoints, with heart failure events only rarely captured as dedicated outcomes, and operative technique, cardiovascular comorbidity, and frailty are often treated as separate domains rather than components of an integrated risk framework. Materials and Methods: We conducted a systematized narrative review with a structured literature search in PubMed/MEDLINE, Scopus, and Web of Science from inception to 31 January 2026, including original studies of adult patients undergoing breast-conserving surgery, mastectomy, and/or reconstruction that reported early postoperative outcomes in relation to comorbidities, cardiovascular risk, or frailty. Eligibility assessment, data extraction, and qualitative synthesis followed key PRISMA 2020 principles, and findings were organized into three prespecified domains: surgical complexity, cardiovascular vulnerability (including patients with heart failure where reported), and frailty. Results: Nineteen studies (retrospective cohorts, registry-based analyses, and large database studies, primarily ACS NSQIP) met inclusion criteria, encompassing diverse breast surgery populations, including elderly, metastatic, and reconstructive cohorts. Across datasets, escalation from breast-conserving surgery to mastectomy and then to increasingly complex reconstruction was associated with a stepwise increase in perioperative complications, reoperations, bleeding, and, in selected series, catastrophic events. Preexisting cardiovascular disease and systemic vascular pathology significantly amplified postoperative morbidity even in procedures considered low or intermediate cardiac risk, with signals that patients with underlying heart failure carry particularly heightened vulnerability, although HF-specific events were infrequently reported as separate endpoints. Frailty, mainly assessed using modified frailty indices, consistently emerged as a strong, age-independent predictor of 30-day complications, mortality, and readmissions across surgical types, including both breast-conserving and reconstructive procedures. Conclusions: Early postoperative outcomes after breast cancer surgery are associated with the interaction between surgical complexity, cardiovascular comorbidity (with limited HF-specific reporting), and frailty rather than by operative technique alone. In this context, our synthesis primarily reflects overall cardiovascular vulnerability in comorbid and frail patients, with heart failure risk inferred indirectly from the available data. These findings support a patient-centered, risk-adapted surgical strategy in which the extent and timing of surgery and reconstruction are tailored to each patient’s cardiovascular profile and frailty status, with preferential use of breast-conserving or less complex procedures in vulnerable individuals. Integrating standardized frailty assessment and cardio-oncologic evaluation into preoperative workflows, and prospectively validating this tri-axial framework in dedicated cohorts, may improve perioperative risk stratification and reduce the burden of postoperative medical complications in an aging breast cancer population. Full article

Cardiovascular diseases have high mortality rates and present a high burden on society and the global healthcare system. A large quantity of drugs have been developed, such as aspirin, ACE inhibitors, beta-blockers, and statins. Although these traditional drugs have decreased the morbidity and mortality of cardiovascular diseases, they still have multiple limitations. Due to their shortcomings, researchers have continued to search for novel targets for drug treatment. The tripartite motif (TRIM) protein family is a superfamily with E3 ubiquitin ligase activity and involves diversified processes including proliferation, development, signal transduction, and immune regulation. The latest research has shown that TRIM proteins participate in the progression of cardiovascular diseases, such as cardiac hypertrophy, cardiac ischemia–reperfusion injury, heart failure, hypertension, atherosclerosis, and so on. In this review, we summarize the structure and function of TRIM proteins, as well as the mechanisms of their involvement in various cardiovascular diseases, aiming to raise awareness of the importance of TRIM proteins in cardiovascular disease research and treatment. Advancing our understanding of mechanisms mediated by TRIM proteins may emphasize their contributions to cardiovascular diseases and provide the opportunity to develop novel and targeted therapeutic strategies to combat cardiovascular diseases. Full article

Transcatheter aortic valve replacement (TAVR) has transformed the management of severe aortic stenosis and is now widely used across a broad spectrum of surgical risk. With expanding indications and increasing use in younger patients, contemporary practice increasingly emphasizes lifetime management of aortic valve disease, a shift further supported by recent developments including findings from the EARLY TAVR trial and the May 2025 U.S. Food and Drug Administration approval of TAVR for asymptomatic severe aortic stenosis. This narrative review summarizes recent developments in TAVR, including advances in device technology, procedural techniques, and patient selection. Focus is placed on the importance of optimal first valve selection, prevention of prosthesis–patient mismatch (PPM), and planning for future reintervention such as valve-in-valve (ViV) TAVR. Emerging procedural strategies including bioprosthetic valve fracture and leaflet modification techniques have expanded treatment options for patients at risk of elevated gradients or coronary obstruction. The review also highlights evolving approaches to TAVR in complex clinical scenarios and discusses future directions in device design and imaging-based procedural planning. As TAVR continues to evolve, careful procedural planning and multidisciplinary heart team collaboration remain essential to optimizing long-term outcomes. Full article

Cardiometabolic disease is increasingly shaped by the overlap among obesity, type 2 diabetes, chronic kidney disease, heart failure, and atherosclerotic cardiovascular disease, underscoring the need for prevention strategies that extend beyond glucose-centered care. This narrative review critically examines the mechanistic rationale, clinical evidence, guideline evolution, and practical implementation of sodium-glucose cotransporter-2 inhibitors (SGLT-2 inhibitors) and glucagon-like peptide-1 receptor agonists (GLP-1 receptor agonists) within the cardiorenal–metabolic continuum. A structured literature search was conducted in PubMed, Scopus, and Web of Science, focusing primarily on publications from January 2019 to March 2026, with selected landmark studies from earlier years included for context. Priority was given to randomized controlled trials, major cardiovascular and kidney outcome trials, meta-analyses, clinical practice guidelines, scientific statements, and expert consensus documents. The reviewed evidence indicates that SGLT-2 inhibitors show the most consistent benefits in reducing heart failure events, slowing chronic kidney disease progression, and lowering cardiorenal risk, whereas GLP-1 receptor agonists are more strongly associated with reductions in major adverse cardiovascular events, residual atherosclerotic risk, and body weight. Emerging data also support extension of this therapeutic paradigm beyond diabetes, particularly in obesity-associated cardiovascular risk. Contemporary care is increasingly moving toward phenotype-informed treatment selection, earlier organ-protective intervention, and multidisciplinary management, although cost, access, tolerability, and implementation barriers remain important limitations. SGLT-2 inhibitors and GLP-1 receptor agonists are therefore central to modern cardiovascular prevention across the cardiovascular–kidney–metabolic spectrum. In this context, the proposed Cardiometabolic 2.0 framework may serve as a clinically oriented model for integrating these therapies within contemporary organ-protective care. Full article

Cardiovascular diseases remain the leading cause of mortality worldwide, and one of the key mechanisms driving the development of heart failure is pathological remodeling of the myocardium. This process involves complex structural, cellular, and metabolic alterations in which the immune system and its interactions with cardiomyocytes and fibroblasts play a central role. The aim of this work was to present the current state of knowledge on immunometabolism in cardiac remodeling and to discuss its pathophysiological relevance and therapeutic potential. This review focuses on the metabolism of cardiac macrophages, highlighting the differences between the pro-inflammatory (M1) and reparative (M2) phenotypes and their impact on inflammation, fibrosis, and myocardial regeneration. The roles of major metabolic pathways, including glycolysis, oxidative phosphorylation, fatty acid oxidation, and glutaminolysis, are discussed, as well as the importance of the NLRP3 inflammasome and efferocytosis in regulating the inflammatory response. Furthermore, the review briefly incorporates recent insights into neutrophil, T cell, and regulatory T cell (Treg) metabolism and their contributions to inflammation, repair, and fibrotic remodeling. Particular attention is also given to cardiac fibroblasts and their metabolic reprogramming during fibrosis, with emphasis on the pivotal role of transforming growth factor-β (TGF-β) signaling. The review further discusses the role of microRNAs as mediators of intercellular communication integrating immunological and metabolic signals. The work is complemented by a discussion of therapeutic perspectives, including modulation of macrophage metabolism, fibrogenic signaling pathways, mitochondrial function, and miRNA-based therapies. Immunometabolism emerges as a promising research field whose further exploration may contribute to the development of novel, more precise strategies for the treatment of cardiovascular diseases. Full article

Introduction: Propofol is one of the most commonly used intravenous anesthetics worldwide and is considered safe for all age groups. However, there have been reports that propofol can induce severe atrioventricular block in humans, and several studies have shown that propofol hinders or prevents the inducibility of arrhythmias during electrophysiological studies (EPS) and radiofrequency (RF) ablation. Objectives: To compare arrhythmia inducibility during electrophysiological study and radiofrequency ablation in pediatric patients with Wolff–Parkinson–White syndrome undergoing propofol-based sedation versus sevoflurane-based general anesthesia. Methods: We conducted a retrospective observational cohort study including 45 pediatric patients aged 0–18 years. Patients were identified through a review and analysis of a database of individuals with Wolff–Parkinson–White syndrome who were referred for electrophysiological study and/or radiofrequency ablation at the Electrophysiology Laboratory of the Institute of Cardiology (IC/FUC) in Porto Alegre over the past five years (2019–2024). Patients with prior ablation, structural heart disease, or ongoing antiarrhythmic therapy were excluded. The patients were divided into two groups and designated as group S (who received sedation) or group G (who received general anesthesia). Sedation (group S) was performed with midazolam (0.08–0.2 mg/kg), fentanyl (0.1–0.2 μcg/kg), and propofol 50–60 µg/kg/min in continuous infusion. General anesthesia (group G), in turn, was performed with sevoflurane at an average dose of 2% (1 MAC according to age). Results: From 4874 invasive electrophysiology procedures performed during the study period, 45 involved pediatric patients with WPW. The sedation group (n = 29) had significantly older patients (14.6 ± 2.5 vs. 10.3 ± 2.8 years, p < 0.001) with higher weight (65.9 ± 16.3 vs. 41.2 ± 7.8 kg, p < 0.001) compared to the general anesthesia group (n = 16). Arrhythmia was successfully induced in 15/29 (51.7%) patients in the sedation group compared to 13/16 (81.2%) in the general anesthesia group (p = 0.062, Fisher’s exact test). Although this difference did not reach statistical significance, it represents a clinically relevant 29.5% lower induction rate in the sedation group. Post hoc power analysis revealed the study was underpowered (49.8%), suggesting a possible Type II error. Analysis of the “procedure room time” revealed a longer duration in the general anesthesia group (97.8 ± 36.7 vs. 67.8 ± 24.4 min), and this difference was statistically significant (p = 0.002). Conclusions: This study compared propofol-based sedation with sevoflurane-based general anesthesia in pediatric WPW patients. While sedation with propofol did not show a statistically significant reduction in arrhythmia inducibility, there was a concerning trend toward lower induction rates (29.5% difference) that may be clinically relevant. The study’s limited statistical power (49.8%) suggests these findings should be interpreted cautiously, and larger prospective studies are needed to definitively establish whether propofol affects arrhythmia inducibility in this population. Propofol remains a viable option for these procedures, but clinicians should be aware of the potential for reduced inducibility, particularly in cases where arrhythmia induction is critical for diagnosis and treatment. Full article

Emery–Dreifuss muscular dystrophy (EDMD) is a rare inherited neuromuscular disorder within the spectrum of nuclear envelope diseases, classically characterized by early musculo-tendinous contractures, slowly progressive myopathy, and cardiac involvement dominated by conduction disease and arrhythmias, with variable evolution toward cardiomyopathy and heart failure. This narrative review provides a comprehensive and clinically actionable synthesis of cardiovascular manifestations across EDMD genotypes and phenotypes, outlining pragmatic diagnostic and therapeutic pathways for real-world care. A targeted literature search was performed in PubMed, Embase, and Web of Science, focusing on studies addressing cardiovascular involvement in EDMD. Relevant original studies, case series, registries, guideline documents, and high-quality reviews were selected and synthesized narratively, with particular emphasis on diagnostic strategies, risk stratification, and management approaches. Cardiac involvement in EDMD encompasses a broad and heterogeneous spectrum, including atrial disease and conduction disturbances, ventricular arrhythmias, dilated cardiomyopathy, thromboembolic complications, and sudden cardiac death. Phenotypic expression varies according to the underlying genetic substrate, with distinct atrial- and ventricular-dominant trajectories. Early recognition and structured cardiovascular surveillance are essential to guide timely intervention, including anticoagulation, device therapy, and heart failure management. Despite growing awareness, significant gaps remain in risk prediction and standardized management strategies. EDMD represents a paradigmatic model of cardiomyopathy characterized by prominent electrical instability and systemic involvement. A structured, genotype- and phenotype-informed approach centered on early surveillance, proactive arrhythmia and thromboembolic risk management and timely device therapy may improve clinical decision-making in real-world settings. Future perspectives include the integration of precision medicine and the development of gene- and pathway-targeted therapies, with the potential to shift from symptomatic management toward disease-modifying strategies. Full article

Cyanotic congenital heart disease (CCHD) remains a major contributor to infant morbidity and mortality in the United States, yet the influence of maternal social determinants of health on risk is not fully understood. This study examined associations of maternal age, education, and race/ethnicity with the live birth prevalence of CCHD using recent national birth data from the Centers for Disease Control and Prevention (CDC) National Vital Statistics System (2022–2023). CCHD was identified from birth certificate records and analyzed as a binary outcome. Regression analyses were performed to evaluate relationships between maternal characteristics and CCHD occurrence. Overall, CCHD was a rare outcome with a modest decline in prevalence between the two years examined. Increasing maternal age was associated with higher odds of CCHD, while Latina ethnicity was associated with lower odds compared to the reference group. Other racial/ethnic categories and maternal education level were not significantly associated with CCHD risk in adjusted analyses. These findings suggest that certain maternal factors, particularly age and ethnicity, are associated with variation in the live birth prevalence of CCHD and underscore the need for further research into underlying environmental and structural contributors not captured in standard birth records. Full article

Disease-specific alpha-synuclein (αsyn) strains have been linked to different synucleinopathies. Current αsyn biomarkers are limited to binary detection of pathogenic αsyn in peripheral tissue biopsies or fluids, limiting differential diagnosis. Hence, there is an urgent need for methods that allow strain-specific detection and characterization of αsyn strain architecture. Notably, luminescent conjugated oligothiophenes (LCOs) have been successfully used to detect distinct protein strain conformers in prion diseases and Alzheimer’s disease, highlighting their utility in differentiating disease-specific amyloid structures. Species-dependent differences in αsyn structure are increasingly recognized as one of the critical aspects that shape how fibrils form, propagate and interact with molecular LCO probes. Here, we evaluate the potential of the LCO h-FTAA to differentiate species-specific αsyn strains and conduct a translational investigation using peripheral cardiac tissue of a gut-first synucleinopathy rodent model. Our in vitro data demonstrate strain-specific probe–fibril interactions, reflecting a differential strain architecture and cellular micro-environment. While h-FTAA binds with comparable efficiency to mouse (mo-) and human (hu-) pre-formed fibrils (PFFs), h-FTAA exhibits markedly lower quantum yield when bound to moPFFs versus huPFFs. Spectral imaging revealed h-FTAA-moPFF binding produces blue-shifted maxima (505–550 nm), contrasting with the red-shifted maxima (545–580 nm) of huPFFs. Fluorescence lifetime imaging microscopy confirmed h-FTAA’s intrinsic sensitivity to species-dependent variations through distinct temporal fluorescence signatures (moPFFs: ~0.60–1.5 ns vs. huPFFs: ~0.65–1.0 ns). Our translational investigation showed h-FTAA binding to peripheral cardiac pathology exhibits comparable red-shifted emission, but distinct fluorescence lifetimes of h-FTAA-bound aggregates in moPFF-injected (~1.0–1.4 ns) versus huPFF-injected (~0.69–0.8 ns) rats. Interestingly, we observed distinct blue-shifted emission profiles in a few selected regions of the heart of moPFF-injected rodents, further characterized by extra-long fluorescence decay shifts (~1.5–1.9 ns), reflecting differences in both aggregate conformation and maturity in moPFF-induced compared with huPFF-induced rats. Taken together, our findings underscore the potential of LCO ligands, like h-FTAA, to enable more precise disease staging and diagnosis through peripheral biopsies, complementing existing αsyn biomarker methods. Full article

Background and Objectives: Idiopathic ventricular arrhythmias commonly occur in patients without structural heart disease and most often present as premature ventricular contractions (PVCs). Although generally considered benign, a high PVC burden may cause symptoms, reduce quality of life, and lead to reversible PVC-induced cardiomyopathy. This study aimed to evaluate long-term outcomes after radiofrequency catheter ablation of idiopathic outflow tract PVCs. Materials and Methods: This single-center retrospective study included 101 patients with idiopathic PVCs who underwent radiofrequency catheter ablation. PVC burden and clinical outcomes were assessed at baseline and during follow-up at 3 months, 12 months, and 5 years. Procedural success, predictors of success, and changes in antiarrhythmic drug therapy were analyzed. Results: During follow-up, a marked reduction in PVC burden was observed compared with baseline values. The median PVC burden decreased from 21.89% at baseline to 0.79% at 3 months, 0.23% at 12 months, and 0.09% at the 5-year follow-up after ablation. Acute procedural success was achieved in 88.1% of patients. Long-term success at 5 years was observed in 80.2% of patients. The use of antiarrhythmic drugs decreased during follow-up. Left ventricular ejection fraction remained stable, with no significant difference between baseline and 5-year values. Monomorphic PVC morphology and procedural success at 12 months were identified as independent predictors of long-term success. Conclusions: Radiofrequency catheter ablation provides effective and sustained reduction in PVC burden in patients with idiopathic outflow tract PVCs, with high acute success rates, durable long-term outcomes, and reduced reliance on antiarrhythmic drug therapy. Full article

Background: Trace elements function as essential micronutrients involved in oxidative balance, mitochondrial activity, and cardiovascular metabolism. Cigarette smoking represents a significant source of toxic metals and may disrupt systemic trace element homeostasis. Alterations in micronutrient and metal balance may contribute to oxidative stress, endothelial dysfunction, and myocardial remodeling, which are central mechanisms in the pathogenesis of heart failure with preserved ejection fraction (HFpEF). This study aimed to investigate whether smokers with HFpEF exhibit distinct hair trace element profiles compared with smokers without HFpEF. Methods: In this prospective pilot study, scalp hair samples were collected from adults undergoing clinical evaluation for suspected cardiovascular disease. Trace element concentrations were determined using inductively coupled plasma mass spectrometry (ICP-MS). Participants were first stratified according to smoking status and subsequently, within the smoker subgroup, according to HFpEF diagnosis based on the Heart Failure Association Pre-test assessment, Echocardiography and natriuretic peptide score (HFA-PEFF) algorithm. Differences in trace element concentrations were analyzed using appropriate statistical tests, with multiple-comparison correction using the Benjamini–Hochberg false discovery rate (FDR). Active smoking was defined as ≥10 cigarettes per day for at least 1 year, and cumulative exposure was quantified in pack-years. Results: Fifty-eight participants were included, including 27 active smokers. In unadjusted analyses, several trace elements differed between smokers with HFpEF and those without HFpEF, including vanadium, lithium, aluminum, and copper. However, after FDR correction, only copper remained significantly elevated in smokers with HFpEF (q = 0.004). Hair copper concentrations were markedly higher in the HFpEF group compared with smokers without HFpEF. These differences were observed alongside echocardiographic features consistent with diastolic dysfunction and structural cardiac remodeling. Conclusions: In this hypothesis-generating pilot study, smokers with HFpEF demonstrated elevated hair copper concentrations, suggesting disturbances in trace element and micronutrient homeostasis. Altered copper metabolism may reflect oxidative stress-related cardiometabolic remodeling associated with HFpEF. These findings raise the hypothesis that cardiometabolic phenotype, rather than smoking exposure alone, may modulate trace element homeostasis in HFpEF; however, causal relationships cannot be established. Full article

Background/Objectives: Congenital heart defects (CHDs) are the most common congenital anomalies, and survival into adolescence and adulthood now exceeds 90%. Increasing evidence suggests that children and adolescents with CHD face elevated risks of psychological, psychiatric and neurodevelopmental disorders. This systematic review aims to synthesize recent evidence on mental health outcomes, cognitive profiles, quality of life and associated risk factors in pediatric CHD. Methods: This review was conducted according to PRISMA 2020 guidelines. Five databases (PubMed/MEDLINE, Embase, Scopus, Web of Science, Cochrane Library) were searched for studies published between January 2015 and November 2025. Eligible studies (observational, interventional and neuroimaging) included participants aged 0–18 years with any type of CHD and reported psychological, psychiatric, neurodevelopmental, cognitive or health-related quality-of-life outcomes. Due to substantial heterogeneity, findings were synthesized narratively. Results: Sixty-one studies involving over 120,000 participants were included. Children and adolescents with CHD showed increased prevalence of anxiety, depression, attention-deficit/hyperactivity disorder, autism spectrum disorder and post-traumatic stress symptoms compared with peers without CHD. Neurodevelopmental impairments, particularly in executive functioning, attention and memory, were frequently reported, especially in complex CHD and single-ventricle physiology. Health-related quality of life was consistently reduced, mainly in emotional and social domains. Parental mental health, disease severity and cumulative medical burden were significant correlates. Neuroimaging studies identified structural and functional brain alterations associated with cognitive and emotional vulnerability. Conclusions: Pediatric CHD is associated with substantial psychological and neurodevelopmental burden, particularly in complex disease. Early identification and integration of routine psychological care within multidisciplinary CHD programs are essential to improve long-term outcomes. Full article

Transcatheter aortic valve implantation (TAVI) has transformed the management of severe aortic stenosis (AS), evolving from a therapy reserved for inoperable patients to a viable treatment across the spectrum of surgical risk. This success has stimulated innovation in transcatheter therapies for other valvular heart diseases, including aortic regurgitation (AR). In contrast to AS, AR is characterised by heterogeneous aetiologies, absence of annular calcification, larger and more elliptical annular dimensions, and concomitant aortopathy. These challenges have limited the efficacy and safety of conventional transcatheter aortic valves (TAVs), use of which in pure native AR is associated with high rates of valve embolisation, significant residual regurgitation, permanent pacemaker implantation, and mortality. The development of dedicated TAVs designed specifically for the treatment of AR has addressed many of these anatomical challenges. The JenaValve Trilogy and J-Valve systems incorporate leaflet-grasping mechanisms that enable secure anchoring independent of calcification, resulting in transformation of procedural and clinical outcomes. Recent prospective registry data, including the landmark ALIGN-AR trial, demonstrate high technical and procedural success rates, low residual regurgitation, acceptable safety profiles, and meaningful improvements in functional status and ventricular remodelling. These data have informed contemporary guideline updates, with the 2025 European Society of Cardiology (ESC)/European Association of Cardiothoracic Surgery (EACTS) Guidelines for the management of valvular heart disease issuing the first conditional recommendation for TAVI in selected patients with severe AR and the National Institute for Health and Care Excellence (NICE) recommending TAVI for native AR in patients for whom surgical AVR is not available or is high risk. This review summarises the clinical implications of AR, examines current guideline recommendations for management, and critically appraises the evidence supporting transcatheter treatment strategies. Full article

Heart disease remains a leading cause of mortality worldwide, and timely and accurate diagnosis is crucial for improving patient outcomes. Medical imaging plays a pivotal role in this process, yet traditional diagnostic methods often suffer from limitations, including dependency on manual interpretation, susceptibility to observer variability, and inefficiency in handling large-scale data. Deep learning has emerged as an innovative technology in medical imaging, providing unparalleled advancements in feature extraction, segmentation, classification, and prediction tasks. Despite its proven potential, comprehensive reviews of deep learning methods specifically targeted at cardiac imaging remain scarce. This review paper seeks to bridge this gap by analyzing the state-of-the-art deep learning applications for heart disease diagnosis, covering the period from 2015 to 2025. Employing a well-structured methodology, this review categorizes and examines studies based on imaging modalities: Ultrasound (US), Magnetic Resonance Imaging (MRI), X-ray, Computed Tomography (CT), and Electrocardiography (ECG). For each modality, the analysis focuses on utilized datasets, processing techniques (e.g., extraction, segmentation and classification), and paradigms (e.g., transfer learning, federated learning, explainability, interpretability, and uncertainty quantification). Additionally, the types of heart disease addressed and prediction accuracy metrics are also scrutinized. These findings point toward future opportunities, including the study of data quality, optimization, transfer learning, uncertainty quantification and model explainability or interpretability. Furthermore, exploring advanced techniques such as recurrent expansion, transformers, and other architectures may unlock new pathways in cardiac imaging research. This review is a critical synthesis offering a roadmap for researchers and practitioners to advance the application of deep learning in heart disease diagnosis. Full article

Arterial stiffness has traditionally been interpreted as a marker of vascular ageing and cumulative blood pressure exposure. Increasing evidence, however, indicates that it should be viewed as an active determinant of cardiovascular loading conditions rather than a passive epiphenomenon. By accelerating pulse wave velocity and altering the timing of wave reflection, large artery stiffening increases central systolic pressure, augments late systolic load, and facilitates the transmission of pulsatile energy to the microcirculation. These hemodynamic alterations shape ventricular remodeling, influence ventricular–vascular coupling, and contribute to organ vulnerability even when brachial blood pressure appears adequately controlled. In this review, population-based observations and mechanistic human studies are integrated to position arterial stiffness as a stage-dependent dimension of cardiovascular disease. Community data illustrate its association with different blood pressure phenotypes and early cardiac structural changes, whereas evidence from advanced heart failure settings helps contextualize arterial stiffness within states of marked autonomic activation. Taken together, this perspective suggests that arterial stiffness is not merely a marker of cumulative damage, but a mediator that contributes to disease progression across clinical stages and, in practical terms, a phenotyping dimension along the trajectory from hypertension to heart failure. Full article