Many patients with heart failure (HF) progress to an advanced stage, characterized by persistent symptoms despite maximal therapy. Heart transplantation (HT) remains the most effective treatment option for improving the survival of patients with advanced HF. This is true even with advancements in medical therapy for HF and the development of mechanical circulatory support systems. Over the past few decades, HT has undergone significant evolution, leading to greatly improved success rates. However, HT recipients face the risk of several potential complications that can negatively impact their outcomes. In this article, we aim to provide a practical framework for clinicians involved in heart transplant medicine. Additionally, we offer an update on a recent and relatively unknown complication of HT: eosinophilic myocarditis (EM).

Background. Atherosclerosis is a long-standing process that starts in childhood and leads to a number of major adverse cardiovascular events in adulthood. It is therefore crucial that children at potential risk of atherosclerosis-related harmful consequences are identified. Nevertheless, relatively few studies have focused on primary prevention in paediatric patients. Methods. Fifty-four children (mean age 9.0 ± 2.8 years) and 72 parents (mean age 44.0 ± 8.2 years) were recruited. Blood pressure (BP) was measured and lipid panel was checked, together with carotid intima-media thickness (IMT) and several indexes of carotid stiffness. Results. No statistically significant differences in IMT and indexes of carotid stiffness were detected between children and parents, with the exception of the alpha index (p < 0.05). In children, IMT was correlated with the alpha index (p = 0.01). Seventeen children (31%) had a pathological IMT. The diastolic BP difference between children with normal and pathological IMT was statistically significant (p < 0.05). Parents' total, LDL and HDL cholesterol, as well as triglyceride levels, differed statistically from those of children with both physiological and pathological IMT: p < 0.05 for all differences. Children with hypercholesterolemia had a three-fold higher likelihood of having a pathological IMT than children with normal cholesterol (p < 0.01). Among children with pathological IMT, 59 percent had one and 41 percent had two parents who were affected by pathological IMT. Conclusions. Carotid stiffness was similar in children and their parents, suggesting early familial influences on vascular properties. Many children had a pathological carotid IMT, highlighting how subclinical atherosclerosis is diffuse even at a young age. IMT in children was associated with cholesterol levels, underscoring the importance of early lipid screening and management. The strong association between pathological IMT in both children and their parents supports the hypothesis of a shared genetic or environmental predisposition to early vascular alterations.

Isometric resistance training (IRT) has emerged as a promising non-pharmacological intervention for blood pressure (BP) management. Although current hypertension guidelines primarily recommend aerobic and dynamic resistance exercise, growing evidence indicates that IRT is an effective, feasible, and time-efficient alternative. This narrative review summarizes the current evidence on the efficacy, physiological mechanisms, and clinical applications of IRT. We reviewed randomized controlled trials, systematic reviews, and meta-analyses evaluating the effects of different IRT modalities, including isometric handgrip (IHG), isometric wall squat (IWS), and isometric leg extension (ILE), on BP in normotensive individuals, patients with hypertension, and those with cardiovascular disease. IRT consistently reduces resting systolic BP by approximately 5-8 mmHg and diastolic BP by 3-4 mmHg; these effects may approach those reported with first-line antihypertensive therapy and potentially be equivalent to those of other exercise modalities. These benefits have been demonstrated across normotensive and hypertensive populations and appear largely independent of age, sex, medication use, and the muscle groups involved. Preliminary evidence also supports the feasibility and safety of appropriately prescribed IRT in selected patients with ischemic heart disease and heart failure with preserved ejection fraction. Proposed mechanisms include improvements in endothelial function, nitric oxide bioavailability, autonomic regulation, oxidative stress, arterial baroreflex sensitivity, and myocardial efficiency. IRT has emerged as an effective, safe, and practical adjunct to lifestyle modification for BP control, particularly in older adults and individuals with limited ability to perform conventional exercise. However, current evidence derives from relatively small studies with limited follow-up; further large-scale randomized trials are needed to define the optimal exercise prescription, clarify the underlying mechanisms, and establish the role of IRT in patients with cardiovascular disease.

Epicardial adipose tissue (EAT) is a metabolically active visceral fat depot implicated in cardiometabolic and cardiovascular (CV) disease. Although cardiac magnetic resonance (CMR) and cardiac computed tomography (cCT) enable accurate volumetric quantification of EAT, their cost, limited availability, and—particularly for cCT—radiation exposure, restrict their use in preventive and longitudinal settings. Transthoracic echocardiography (TTE) is widely accessible and radiation-free, but its validity as a surrogate of volumetric EAT assessment and its broader clinical role remain incompletely defined. To systematically synthesize disease-specific evidence linking TTE-derived EAT thickness with major CV phenotypes and to quantitatively assess its association with volumetric EAT measured by CMR or cCT. A systematic search of PubMed and PubMed Central (January 2000–December 2025) identified adult studies evaluating associations between TTE-derived EAT thickness and coronary artery disease (CAD), atrial fibrillation (AF), or heart failure with preserved ejection fraction (HFpEF), and correlations between TTE-derived EAT thickness and CMR- or cCT-derived EAT volume. Correlation coefficients were pooled using a random-effects model after Fisher’s z-transformation. An exploratory meta-analysis assessed associations with major adverse cardiovascular events (MACE). Seventeen disease-specific studies consistently demonstrated associations between increased TTE-derived EAT thickness and CAD severity, AF burden and recurrence, and adverse HFpEF phenotypes. Five validation studies were included; four comparing TTE with CMR were pooled, yielding a moderate-to-strong correlation (r = 0.77, 95

This study investigated the effect of eight weeks of interval training on insulin signaling and neurodegeneration in the hippocampus of methamphetamine (METH)-treated rats. Thirty-two male Wistar rats were randomly divided into four equal groups (n = 8): saline, METH-1 (21-days of injection period), METH-2 (21-day injection period, followed by 8-week withdrawal), and METH+moderate-intensity interval training (MIT). Methamphetamine was injected intraperitoneally at 5 mg/kg per day for a period of 21 consecutive days. MIT was conducted on a treadmill at 60–65% of maximum speed, 5 days weekly for 8 weeks. At the end of the injection and training period, the hippocampal tissue of rats was extracted to evaluate the pathological changes and gene expression of related indicators. METH injection caused a disturbance in the insulin signaling pathway, resulting in increased neurodegeneration, as evidenced by a decrease in the expression of IRS-1 (p < 0.001) and Akt (p < 0.001) genes as well as an increase in the expression of GSK-3β (p < 0.001), APP (p = 0.007), tau (p = 0.006), p-tau (p < 0.001), and Caspases-3 (p = 0.003) genes. However, MIT significantly upregulated the expression of IRS-1 (p < 0.001) and Akt (p = 0.002), while downregulating APP (p = 0.028) and p-tau (p < 0.001). These findings suggest that MIT enhances insulin signaling activity and improves anxiety-like behaviors, thereby counteracting the detrimental effects of METH. Further studies are required to expand and validate these findings.

Cardiac positron emission tomography (PET) has undergone substantial development in recent years, moving beyond conventional perfusion imaging toward a multiparametric and increasingly quantitative assessment of cardiovascular disease. This article provides a critical narrative overview of the recent cardiac PET literature, with particular emphasis on studies published over the last five years, and discusses both established tracers and emerging radiopharmaceuticals in contemporary cardiology. Among established applications, 18F-FDG remains relevant for myocardial viability assessment and selected inflammatory indications, although its prognostic and therapeutic implications are less uniform than earlier narratives suggested. For myocardial perfusion imaging, 13N-ammonia and 82Rb PET provide robust assessment of myocardial blood flow and myocardial flow reserve, but their clinical interpretation remains strongly influenced by acquisition protocols, software reproducibility, and methodological standardization. The review also addresses newer tracers, including 68Ga-FAPI for fibroblast activation, 18F-flurpiridaz for high-performance perfusion imaging, 18F-FDOPA for cardiac sympathetic dysfunction, and amyloid-binding PET radiopharmaceuticals for cardiac amyloidosis. Overall, recent evidence supports cardiac PET as a powerful platform for physiologic and molecular imaging, but not as a uniform or methodologically neutral technology. Its current value lies in selective, question-driven clinical use, whereas broader implementation will depend on tracer-specific validation, harmonized quantitative workflows, and clear demonstration of incremental benefit over existing imaging strategies.

Background: Right heart failure (HF) and tricuspid regurgitation (TR) are closely interrelated conditions, linked by a bidirectional and self-perpetuating pathophysiological relationship. Alterations in right-ventricular (RV) loading conditions, pulmonary vascular impedance, and ventriculo-arterial (VA) coupling play a central role in the development and progression of TR, which in turn exacerbates RV volume overload and end-organ dysfunction. Methods: This review provides a comprehensive overview of the pathophysiology of right HF and TR, focusing on the mechanisms underlying RV dysfunction, pressure-volume (PV) relationships, and pulmonary vascular load. We further examine the clinical implications of this interaction and summarize current strategies for risk stratification, with particular emphasis on disease-specific risk models. Results: TR emerges both as a consequence and a driver of RHF. Conditions such as pulmonary hypertension (PH) and left-sided heart disease promote annular dilation and leaflet tethering, leading to functional TR. Conversely, TR increases RV volume overload, worsening chamber dilation, reducing effective forward stroke volume (SV), and accelerating disease progression. This vicious cycle results in progressive RV impairment, impaired left-ventricular filling through ventricular interdependence, and systemic venous congestion affecting renal and hepatic function. Traditional risk scores fail to capture this complex pathophysiology. In this context, TRISCORE integrates clinical, biological, and echocardiographic (TTE) parameters reflecting RV dysfunction and systemic involvement, providing a more comprehensive assessment of disease severity and prognosis. Conclusions: TR should be considered not only a marker but also a key determinant of right HF progression. A multiparametric approach integrating pathophysiology and disease-specific risk stratification is essential to identifying the optimal therapeutic window and guiding clinical decision making.

Mitral stenosis (MS) remains a clinically relevant condition worldwide, with rheumatic and degenerative aetiologies contributing to a broad spectrum of disease. Accurate assessment of MS severity is essential for clinical decision-making but is often challenged by technical limitations, complex hemodynamic interactions, and the heterogeneous anatomical characteristics of different MS aetiologies. This review aims to provide a comprehensive overview of the contemporary multimodality imaging assessment of MS, with particular emphasis on the pitfalls of conventional transthoracic echocardiography (TTE), the incremental value of advanced imaging modalities, and their integration into diagnostic and therapeutic decision-making. A targeted narrative review of the literature was conducted focusing on multimodality imaging approaches and their integration into clinical practice. Particular emphasis was placed on TTE parameters, three-dimensional (3D) TTE, stress echocardiography, transoesophageal echocardiography (TOE), cardiac computed tomography (cCT), and cardiac magnetic resonance (CMR), highlighting their complementary roles in anatomical characterization, hemodynamic assessment, procedural planning, and clinical decision-making. Conventional 2D TTE remains the cornerstone for MS evaluation; however, widely used parameters such as mean transmitral gradient (TMG) and pressure half-time (PHT) are highly load-dependent and may lead to misclassification of disease severity in the presence of altered hemodynamic conditions (e.g., tachycardia, atrial fibrillation (AF), or reduced cardiac output). Although direct planimetry remains the anatomical reference standard, its accuracy may be limited by operator dependency, calcification, and complex valve geometry. In this context, three-dimensional TTE (3D TTE) provides incremental value by enabling more accurate visualization of the mitral valve (MV) orifice and improving measurement reproducibility. Stress TTE plays a key role in patients with discordant symptoms or borderline resting findings by unmasking clinically significant disease during exercise. In selected patients, TOE, cCT, and CMR provide complementary information for the evaluation of complex valve morphology, mitral annular calcification (MAC), ventricular remodelling, and procedural planning, particularly in degenerative mitral stenosis (DMS) and candidates for transcatheter interventions. The evaluation of MS requires an integrated, multiparametric, multimodality imaging approach. Combining conventional TTE with stress imaging and complementary advanced modalities improves diagnostic accuracy, facilitates patient selection for intervention, and supports individualized clinical decision-making, particularly in patients with complex anatomy or discordant imaging findings.

Growing evidence indicates that myocardial infarction (MI) is the clinical manifestation of heterogeneous plaque substrates with distinct molecular, cellular, and biomechanical mechanisms. Acute coronary thrombosis (ACT) most commonly arises from plaque rupture (PR), plaque erosion (PE), and calcified nodules (CNs), each associated with different inflammatory profiles, thrombus composition, clinical presentation, and prognosis. This comprehensive review provides a clinician-oriented synthesis of the pathophysiological mechanisms underlying these three principal plaque phenotypes and discusses their implications for the contemporary management of acute coronary syndromes (ACS). We examine the molecular and cellular determinants of plaque instability and highlight how systemic factors such as plaque burden, impaired healing responses, and myocardial jeopardy modulate clinical risk. The role of intracoronary and non-invasive imaging is discussed primarily as a tool to elucidate plaque biology with direct clinical relevance rather than merely as a procedural guide. Building on these insights, we propose a conceptual framework for integrating plaque biology into clinical decision-making across the acute phase, secondary prevention, and long-term follow-up. In particular, recognizing the biological heterogeneity of plaque substrates may support more personalized therapeutic strategies, enabling clinicians to tailor pharmacological and interventional approaches according to the underlying plaque phenotype and patient-specific risk profile. Finally, we briefly address emerging perspectives, including the potential role of artificial intelligence (AI) in refining plaque characterization, risk stratification, and precision cardiovascular prevention. Overall, recognition of PR, PE, and CNs as biologically distinct entities supports a shift toward mechanism-informed and personalized management of MI, aligning advances in plaque biology with the principles of precision cardiovascular medicine.

Resistant hypertension (RH) is a high-risk phenotype associated with increased cardiovascular and renal morbidity despite multidrug therapy. Dysregulation of the renin–angiotensin–aldosterone system (RAAS), particularly excess aldosterone activity, plays a central role in the pathophysiology of RH. Although conventional RAAS-targeted therapies including angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and mineralocorticoid receptor antagonists improve outcomes, their effectiveness is limited by aldosterone breakthrough, persistent non-genomic aldosterone effects, hyperkalaemia, and off-target adverse effects. Aldosterone synthase inhibitors (ASIs) have emerged as a novel therapeutic strategy targeting CYP11B2, the terminal enzyme responsible for aldosterone biosynthesis. This review summarises the physiological basis of aldosterone synthesis, the pathological consequences of aldosterone excess, and the pharmacological evolution of ASIs. Early-generation agents were limited by inadequate selectivity between CYP11B2 and the closely related CYP11B1 enzyme, resulting in cortisol suppression and deoxycorticosterone accumulation. Advances in structural biology and medicinal chemistry enabled the development of second-generation ASIs with markedly improved selectivity and preserved cortisol biosynthesis. Recent clinical trials of baxdrostat, lorundrostat, vicadrostat, and dexfadrostat have demonstrated clinically meaningful reductions in blood pressure and albuminuria with acceptable safety profiles. Based on the positive trial data, baxdrostat has become the first in class ASI to be approved by regulatory authorities for management of uncontrolled hypertension.

Arterial hypertension and increased Blood Pressure Variability (BPV) are major prognostic determinants in patients with Ischemic Heart Disease (IHD). This randomized pilot study compared the effects of Continuous Combined Training (CCT; moderate-intensity continuous aerobic exercise plus resistance training) and Interval Combined Training (ICT; high-intensity interval aerobic exercise plus resistance training) on BPV and Blood Pressure (BP) parameters. Thirty-six clinically stable patients with IHD and hypertension were randomized to CCT or ICT for 12 weeks. Between-group changes in the study outcome were analysed by ANCOVA. Short-term systolic BPV significantly decreased in the CCT group but remained unchanged in the ICT group: [adjusted between-group difference -2.1 mmHg (95% CI: -3.2 to -1.4; p = 0.036). Resting systolic BP decreased similarly in both groups, whereas no significant changes were observed in 24-hour BP values. Peak oxygen uptake improved in both groups with a greater increase in the ICT group [adjusted between-groups difference +1.7 mL·kg-¹·min-¹ (95% CI: 0.7 to 2.2; p = 0.044). These findings suggest that, in patients with IHD, continuous combined training may be more effective than interval combined training in reducing short-term BPV, whereas interval training may confer greater improvements in aerobic capacity. Further adequately powered studies are warranted to confirm these results.

A broad body of evidence has accrued, demonstrating the role of endothelin-1 (ET-1) in the pathophysiology of pulmonary arterial hypertension. Furthermore, the role of ET-1 as a causative pathophysiological mechanism of portopulmonary hypertension (POPH) has been consistently implicated; however, there is a lack of satisfactory evidence supporting this assertion. Thus, the present study aims to determine the prevalence of POPH among patients with hepatic cirrhosis, determine the serum ET-1 levels among these patients, and investigate the association between ET-1 and POPH in subjects with hepatic cirrhosis. A prospective, observational study was conducted from September 2017 to August 2018. Detailed history and examination with relevant investigations, including echocardiography, were performed for patients with and without POHP. ET-1 levels were significantly higher among patients with POPH compared to those without POPH. Moreover, the ET-1 cut-off level of 82 pg/mL correctly predicted the 9.3% prevalence of POPH in patients with hepatic cirrhosis with 100% sensitivity and 100% negative predictive value. The ET-1 cut-off level of 82 pg/mL may be used as a biomarker of POPH in patients with hepatic cirrhosis.

Background. Cor triatriatum dexter (CTD) is a rare congenital heart defect where a membrane divides the right atrium into two chambers, resulting from the incomplete regression of the right valve of the sinus venosus. Due to its rarity, only individual case reports and a limited number of case series have been published to date. This study constitutes the most extensive comprehensive review conducted in this area. Eight factors were evaluated: age at diagnosis, sex, clinical presentation, electrocardiographic findings, imaging (ultrasound, CT, or MRI), associated cardiac anomalies, and patient outcomes. Methods. The electronic databases PubMed and Scopus were searched from their inception until 30 October 2025. Only case reports and case series were considered for inclusion. Studies involving foetuses, autopsies, and animals were excluded. The collected data were primarily presented as percentages. Results. One hundred fourteen studies were found encompassing 124 patients. The mean age at diagnosis was 33.3 ± 9.4 years The most common clinical presentations were dyspnoea (44.3%) and cyanosis (29.5%). The most commonly encountered ECG changes were supraventricular tachycardia/atrial flutter/atrial fibrillation (33.3%) and right bundle branch block (22.6%). On chest X-ray, cardiomegaly was noted in 46.5%. CTD was suspected or diagnosed by echocardiography in 95.2% of cases. The diagnosis was confirmed by CT and/or MRI in 34.1% of cases. A concomitant congenital heart defect was found in 67.7%, especially in the form of all kinds of atrial septal defect (38.1%) and of right valvular and right ventricular involvement (20.1%). An outcome was reported in 97/124. Surgical correction was the treatment of choice in 51.6%. Since 1991, a percutaneous approach has been employed in selected cases (5.1%). Conservative management was the treatment of choice in 43.3%. The mortality rate was 8.2%. Discussion. The principal limitation of this systematic review lies in its reliance solely on case reports and small case series, reflecting the absence of large-scale studies on CTD. Nonetheless, it constitutes the most comprehensive analysis available to date.

The 2025 Focused Update of the European Society of Cardiology and European Atherosclerosis Society (ESC/EAS) Guidelines for the management of lipid disorders marks a significant evolution in cardiovascular disease (CVD) prevention, reflecting contemporary evidence, advances in risk assessment, and the advent of novel therapeutic modalities. Dyslipidemia remains a primary modifiable risk for atherosclerotic cardiovascular disease, necessitating robust, evidence-driven strategies to optimize prevention. Notably, the update transitions from the traditional SCORE system to the more comprehensive SCORE2 and SCORE2-OP risk models for estimating 10-year atherosclerotic cardiovascular disease risk. These new models broaden applicability, encompassing both fatal and non-fatal cardiovascular events and extending risk calculation up to age 89, while recalibrating country-specific risk clusters and prioritizing non-HDL cholesterol over total cholesterol as a core indicator. The guidelines emphasize the intensification of therapy for individuals identified as being at higher risk, integrating recent clinical trial data and targeted drug selection, with a particular focus on individualized risk stratification. This focused update contrasts its recommendations against the 2019 standard, outlining the rationale for new strategies in both primary and secondary prevention through intensified lipid-lowering therapy. Comprehensive implementation of these recommendations is anticipated to drive further reductions in ASCVD events, aligning with global public health priorities. The 2025 guidelines thus serve as an essential tool for clinicians and researchers, supporting nuanced decision-making and reinforcing the central role of lipid management in contemporary cardiovascular risk reduction.

The benefits of cardiac rehabilitation (CR) have been demonstrated in patients after myocardial infarction (MI), and in patients with chronic heart failure (HF). The core components of the CR program include improvement in exercise tolerance and optimization of coronary risk factors (i.e., lipid and lipoprotein profiles, body weight, blood glucose levels, blood pressure levels, and smoking cessation). Indeed, CR has been shown to improve exercise capacity, control of cardiovascular risk factors, quality of life, hospital readmission, and mortality rates. Nonetheless, pre- and clinical CR and exercise training models are an enormous source of potential beneficial mechanisms that can be exploited for cardiac disease therapy. Consequently, in this review, we aim to explore the unique benefits of CR in HF and coronary artery disease, focusing on the epigenetic mechanisms involved and their translational relevance. These mechanisms may represent novel therapeutic targets to promote functional recovery after cardiac injury, and non-coding RNAs could be predictive biomarkers for CR success in patients.

The role of blood pressure variability (BPV) as an important marker of cardiovascular (CV) health, specifically its relationship with arterial stiffness and left ventricular remodeling in patients with hypertension, was investigated. This review aimed to elucidate the intricate relationship between BPV, arterial stiffness, and cardiac remodeling. BPV, as both a risk factor and a target of treatment, was also evaluated. The results point to the pivotal role of BPV in cardiovascular events, serving as an independent factor contributing to arterial stiffness and adverse left ventricular remodeling. The article concludes that BPV is a modifiable risk factor and that there is a need for an intervention in specific regions. BPV is a therapy target that is significant in the treatment of hypertension. The optimization of risk and prevention needs a multidisciplinary approach involving rehabilitation therapy, which will improve cardiovascular conditions and patient outcomes.

Background: Arterial hypertension and increased blood pressure variability (BPV) are major prognostic determinants in patients with ischemic heart disease (IHD). While exercise training is known to improve blood pressure (BP) control, the effects of different combined exercise modalities on BPV in IHD remain poorly defined. This randomized pilot study compared the effects of continuous combined training (CCT; moderate-intensity continuous aerobic exercise plus resistance training) and interval combined training (ICT; high-intensity interval aerobic exercise plus resistance training) on BPV and BP parameters in hypertensive patients with IHD. Methods: Thirty-six clinically stable patients with IHD and hypertension were randomized to CCT or ICT for 12 weeks. Outcomes included short-term BPV assessed by 24-hour ambulatory BP monitoring, resting and 24-hour BP, and exercise capacity. Results: Short-term systolic BPV significantly decreased in the CCT group but remained unchanged in the ICT group: [adjusted between-group difference −2.1 mmHg (95% CI: −4.1 to −0.1; p 0.029]. Resting systolic BP decreased similarly in both groups, whereas no significant changes were observed in 24-hour BP values. Peak oxygen uptake improved in both groups with a greater increase in the ICT group [adjusted between-groups difference +1.7 mL·kg⁻¹·min⁻¹ (95% CI: 0.7 to 2.8); p = 0.032). Conclusion: These findings suggest that, in patients with IHD, continuous combined training may be more effective than interval combined training in reducing short-term BPV, whereas interval training may confer greater improvements in aerobic capacity. Further adequately powered studies are warranted to confirm these results.