J. Cardiovasc. Dev. Dis., Volume 12, Issue 7 (July 2025) – 33 articles

Myocardial injury following polytrauma is a significant yet often underdiagnosed condition that contributes to acute cardiac dysfunction and long-term cardiovascular complications. This review examines the role of systemic inflammation, oxidative stress, neuro-hormonal activation, and immune dysregulation in trauma-induced myocardial damage. Key immunological markers, including interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), monocyte chemoattractant protein-1 (MCP-1), and adhesion molecules (ICAM-1, VCAM-1), are implicated in endothelial dysfunction, myocardial apoptosis, and ventricular remodeling. The interplay between these factors potentially exacerbates cardiac injury, increasing the risk of heart failure. Biomarker-guided approaches for early detection, combined with advanced imaging techniques such as speckle-tracking echocardiography and cardiac MRI, offer promising avenues for risk stratification and targeted interventions. Anti-inflammatory and oxidative stress-modulating therapies may mitigate myocardial damage and improve outcomes. This article highlights the clinical relevance of integrating immunological markers into diagnostic and therapeutic strategies to enhance the management of trauma-related cardiac dysfunction and reduce long-term morbidity. Full article

Background: Extracorporeal membrane oxygenation (ECMO) requires systemic anticoagulation to prevent clotting, typically using unfractionated heparin (UFH). However, anticoagulation carries a bleeding risk, necessitating monitoring. Activated clotting time (ACT) is a commonly used monitoring tool for UFH anticoagulation. However, systematized evidence linking ACT monitoring with haemostatic complications (bleeding and thrombosis) is missing. Methods: A systematic review (Scopus and PubMed, up to 13 July 2024) including studies reporting on the patients receiving ECMO support with UFH anticoagulation monitored using ACT was performed. Results: A total of 3536 publications were identified, of which 30 (2379 patients) were included in the final review. Thirteen studies found no significant association between ACT values and haemorrhage, while four studies suggested a relationship between elevated ACT levels and bleeding events. Eight studies demonstrated no association between ACT values and the occurrence of thrombosis. Major bleeding was most common (49%, 13 studies with 501 events), while the pooled rate of thrombosis was 25% (16 studies with 309 events) and in-hospital mortality was 51% (17 studies, 693/1390 patients). Conclusions: Despite advancements in ECMO, the optimal approach for anticoagulation monitoring remains undefined. Most studies in this review did not establish a significant relationship between ACT levels and haemostatic complications. Based on the current evidence, ACT does not appear to be a reliable tool for monitoring anticoagulation in patients receiving ECMO, and alternative methods should be considered. Full article

Acute heart failure (AHF) is a clinical syndrome characterized by the sudden onset or rapid worsening of heart failure signs and symptoms, frequently triggered by myocardial ischemia, pressure overload, or cardiotoxic injury. A central component of its pathophysiology is the activation of intracellular signal transduction cascades that translate extracellular stress into cellular responses. Among these, the mitogen-activated protein kinase (MAPK) pathways have received considerable attention due to their roles in mediating inflammation, apoptosis, hypertrophy, and adverse cardiac remodeling. The canonical MAPK cascades—including extracellular signal-regulated kinases (ERK1/2), p38 MAPK, and c-Jun N-terminal kinases (JNK)—are activated by upstream stimuli such as angiotensin II (Ang II), aldosterone, endothelin-1 (ET-1), and sustained catecholamine release. Additionally, emerging evidence highlights the role of receptor-mediated signaling, cellular stress, and myeloid cell-driven coagulation events in linking MAPK activation to fibrotic remodeling following myocardial infarction. The phosphatidylinositol 3-kinase (PI3K)/Akt signaling cascade plays a central role in regulating cardiomyocyte survival, hypertrophy, energy metabolism, and inflammation. Activation of the PI3K/Akt pathway has been shown to confer cardioprotective effects by enhancing anti-apoptotic and pro-survival signaling; however, aberrant or sustained activation may contribute to maladaptive remodeling and progressive cardiac dysfunction. In the context of AHF, understanding the dual role of this pathway is crucial, as it functions both as a marker of compensatory adaptation and as a potential therapeutic target. Recent reviews and preclinical studies have linked PI3K/Akt activation with reduced myocardial apoptosis and attenuation of pro-inflammatory cascades that exacerbate heart failure. Among the multiple signaling pathways involved, glycogen synthase kinase-3β (GSK-3β) has emerged as a key regulator of apoptosis, inflammation, metabolic homeostasis, and cardiac remodeling. Recent studies underscore its dual function as both a negative regulator of pathological hypertrophy and a modulator of cell survival, making it a compelling therapeutic candidate in acute cardiac settings. While earlier investigations focused primarily on chronic heart failure and long-term remodeling, growing evidence now supports a critical role for GSK-3β dysregulation in acute myocardial stress and injury. This comprehensive review discusses recent advances in our understanding of the MAPK signaling pathway, the PI3K/Akt cascade, and GSK-3β activity in AHF, with a particular emphasis on mechanistic insights, preclinical models, and emerging therapeutic targets. Full article

Cardiac rehabilitation should be suggested after mitral valve intervention. Physical exercise is associated with improved cardiorespiratory fitness and clinical outcome and reduced rehospitalization and mortality in patients after heart valve surgery. Tailored assessment is the first step before starting a cardiac rehabilitation program. Physical examination, electrocardiogram, echocardiography, and peak exercise capacity stratify the risk of these patients when prescribing appropriate supervised aerobic and resistance exercise training. Cardiac rehabilitation participation impacts physical capacity, psychosocial function, and prognosis in patients after mitral valve surgery and transcatheter edge-to-edge repair. However, further evidence is needed on the efficacy and safety of cardiac rehabilitation programs, as well as standardization. In this review, we provide a contemporary and comprehensive update on the role of cardiac rehabilitation in patients after mitral valve intervention, after both mitral valve surgery and transcatheter mitral valve implantation. Specifically, we focus our review on the tailored assessment and management of these patients from post-operative to cardiac rehabilitation. Full article

(1) Background: Our aim was to evaluate the diagnostic performance of combined coronary computed tomography angiography (CCTA) and dynamic CT myocardial perfusion imaging (CT-MPI) for detecting hemodynamically significant coronary artery disease (CAD) in patients with intermediate pretest probability. (2) Methods: Patients with an intermediate pretest probability of CAD were retrospectively enrolled. All patients underwent CCTA and dynamic CT-MPI using a third-generation dual-source CT scanner prior to invasive coronary angiography (ICA). Anatomically significant stenosis was defined as ≥50% luminal narrowing on both CCTA and ICA. Fractional flow reserve (FFR) was performed during ICA in selected cases. Hemodynamically significant CAD was defined per vessel as FFR ≤ 0.80, angiographic stenosis ≥70%, or having undergone revascularization. The diagnostic performance of CCTA alone and CCTA combined with CT-MPI was compared against this reference standard. (3) Results: Seventy-four patients (mean age, 66.8 ± 11.1 years; 59 men) were included. The median coronary calcium score was 508.5 Agatston units (interquartile range: 147–1173). ICA and CCTA detected anatomically significant stenoses in 137 (61.7%) and 146 (65.8%) coronary vessels, respectively, and in 62 (83.8%) and 71 (95.9%) patients, respectively. Hemodynamically significant stenosis was present in 56 patients (76%) and 99 vessels (45%). On a per-vessel basis, CCTA alone yielded a sensitivity of 96.7%, specificity of 60.3%, positive predictive value (PPV) of 64.4%, and negative predictive value (NPV) of 96.1%. Combined CCTA and CT-MPI demonstrated a sensitivity of 90.1%, specificity of 84.3%, PPV of 82.7%, and NPV of 91.1%. The area under the receiver operating characteristic curve improved from 0.787 (95% confidence interval: 0.73–0.84) for CCTA to 0.872 (95% confidence interval: 0.82–0.91) for the combined approach (p < 0.05). The median total radiation dose for both CCTA and CT-MPI was 8.05 mSv (interquartile range: 6.71–11.0). (4) Conclusions: In patients with intermediate pretest probability of CAD, combining CCTA with dynamic CT-MPI significantly enhances the diagnostic performance for identifying hemodynamically significant coronary stenosis compared to CCTA alone. Full article

Background: Infective endocarditis after transcatheter aortic valve replacement (TAVR-IE) is a rare but severe complication associated with high morbidity and mortality. The optimal treatment strategy—surgical explantation versus medical therapy—remains uncertain, particularly given the technical demands of TAVR removal and the advanced age of many affected patients. Methods: We conducted a systematic review and meta-analysis of studies comparing the surgical and medical management of TAVR-IE. Primary outcomes included 30-day mortality and 1-year survival. Secondary analyses explored microbiological profiles, patient demographics, prosthesis type, postoperative complications, and surgical indications. A qualitative synthesis of surgical explantation techniques and reconstructive strategies was also performed based on recent consensus recommendations. Results: Three studies comprising 1557 patients with TAVR-IE were included; 155 (10.0%) underwent surgical treatment. Thirty-day mortality was comparable between groups (surgical: 9.7%; medical: 8.4%), while the pooled odds ratio for one-year survival did not reach statistical significance (OR: 1.91, 95% CI: 0.36–10.22; I² = 88%). However, single-center outcomes demonstrated markedly improved survival with surgery (96% vs. 51%). The most common surgical indications included severe valvular dysfunction (50.3%), aortic root abscess (26.5%), and large vegetations (21.3%), in line with current guideline recommendations. Postoperative complications included acute renal failure (10%) and longer hospitalizations (19.8 vs. 18 days), although these were not statistically different. Contemporary explant strategies—such as the Double Kocher, Tourniquet, and Y-incision aortic enlargement techniques—were highlighted as critical tools for surgical success. Conclusions: While underutilized, surgical intervention for TAVR-IE may offer significant survival benefits in select patients, particularly when guided by established indications and performed at high-volume centers. Outcomes depend heavily on timing, surgical expertise, and appropriate patient selection. As TAVR expands to younger populations, TAVR-IE will become increasingly relevant, necessitating early multidisciplinary involvement and broader familiarity with advanced explant techniques among cardiac surgeons. Full article

Aorto-esophageal fistula (AEF) is a condition with an extremely high mortality rate that often causes massive gastrointestinal bleeding, commonly resulting from esophageal perforation due to foreign bodies or aortic aneurysmal malformations. This case report introduces an elderly male patient who experienced hematemesis for longer than 16 h without obvious cause. The patient did not receive relief from endoscopic compression hemostasis. Through computed tomography angiography (CTA), a tortuous and thickened vessel was found in the descending aorta of the patient, which entered the esophagus. The diagnosis was AEF caused by vascular malformation. which has not been previously documented in the literature. Full article

Background/Objectives: Left atrial function can be a tool for risk stratification for hypertrophic cardiomyopathy (HCM). Over the past decade, there has been growing interest in the application of strain analysis for earlier and more accurate prediction of cardiovascular disease prognosis. This study aimed to investigate the performance of left atrial strain analysis compared to conventional left atrial measures in predicting clinical outcomes in Asian patients with HCM. Methods and Results: This was a retrospective study involving 291 patients diagnosed with HCM between 2010 and 2017. Left atrial volumes were assessed using the method of discs in orthogonal plans at both end diastole and end systole. Left atrial (LA) strain was obtained using a post-hoc analysis with TOMTEC software. We tested the various left atrial parameters against outcomes of (1) heart failure hospitalization and (2) event-free survival from a composite of adverse events, including all-cause mortality, ventricular tachycardia (VT)/ventricular fibrillation (VF) events, appropriate device therapy if an implantable cardioverter defibrillator (ICD) was implanted, stroke, and heart failure hospitalization. The patients had a mean age of 59.0 ± 16.7 years with a male preponderance (71.2%). The cumulative event-free survival over a follow-up of 3.9 ± 2.7 years was 55.2% for patients with an abnormal LA strain versus 82.4% for patients without one (p < 0.001). Multivariable Cox regression analyses were performed separately for each LA parameter, adjusting for age, sex, LV mass index, LV ejection fraction (EF), E/e’, the presence of LV outflow tract (LVOT) obstruction at rest, and atrial fibrillation. An analysis showed that all parameters except for LAEF demonstrated an independent association with heart failure hospitalization. Left atrial strain outperformed the rest of the parameters by demonstrating an association with a composite of adverse events. Conclusions: In Asian patients with HCM, measures of left atrial strain were independently associated with heart failure hospitalization and a composite of adverse outcomes. Left atrial strain may be used as a tool to predict adverse outcomes in patients with HCM. Full article

Endurance training induces significant cardiac remodeling, with evidence suggesting that prolonged high-intensity exercise may increase the risk of atrial fibrillation (AF). However, physiological responses differ by event type. This review compares AF-related markers in marathon and ultramarathon runners, focusing on structural adaptations, inflammatory and endothelial biomarkers, and the incidence of arrhythmias. A systematic analysis of 29 studies revealed consistent left atrial (LA) enlargement in marathon runners linked to elevated AF risk and fibrosis markers such as Galectin-3 and PIIINP. In contrast, ultramarathon runners exhibited right atrial (RA) dilation and increased systemic inflammation, as indicated by elevated high-sensitivity C-reactive protein (hs-CRP) and soluble E-selectin levels. AF incidence in marathoners ranged from 0.43 per 100 person-years to 4.4%, while direct AF incidence data remain unavailable for ultramarathon populations, highlighting a critical evidence gap. These findings suggest distinct remodeling patterns and pathophysiological profiles between endurance disciplines, with implications for athlete screening and cardiovascular risk stratification. Full article

(1) Background: In the absence of locally validated tools, the CHA2DS2-VA score has been suggested as a substitute for the CHA2DS2-VASc score. This study compared the potential discrepancies between these scores. (2) Methods: The observational, retrospective, and community-based study included a cohort of 3370 patients with a new diagnosis of atrial fibrillation (AF) between 1 January 2015 and 31 December 2024. (3) Results: AF prevalence was 8.4%, which was significantly higher in men. The mean age was 80.1 (SD ± 6.24) years. Women (42.8%) were older (80.9 SD ± 6.1 vs. 79.5 SD ± 6.23; p < 0.001). Men had more instances of diabetes mellitus, peripheral vascular disease, coronary artery disease, and chronic obstructive pulmonary disease, as well as a higher Charlson Comorbidity Index. Conversely, women exhibited a higher proportion ≥75 years, including cognitive impairment, dyslipidemia, and higher stroke risk, as assessed by the CHA2DS2-VASc score (p < 0.001) but not by the CHA2DS2-VA score (p = 0.071). The CHA2DS2-VA score reduced the sex-based risk stratification differences, and only 3.2% of women were reclassified as being at very low risk (CHA2DS2-VA < 2). (4) Conclusions: The CHA2DS2-VA score notably redefined sex-based thromboembolic risk stratification profiles, with no sex-based disparities in the selection of OAC treatment modality. The clinical utility of CHA2DS2-VA remains a subject of ongoing debate. Full article

Sudden cardiac death represents an unexpected death for which a strong underlying genetic background has been described. The primary causes are identified in cardiomyopathies and channelopathies, which are heart diseases of the muscle and electrical system, respectively, without coronary artery disease, hypertension, valvular disease, and congenital heart malformations. Genetic variants, especially single nucleotide variants and short insertions/deletions impacting essential myocardial functions, have shown that cardiomyopathies display high heritability. However, genetic heterogeneity, incomplete penetrance, and variable expression may complicate the interpretation of genetic findings, thus delaying the management of seriously at-risk patients. Moreover, recent studies show that the diagnostic yield related to genetic cardiomyopathies ranges from 28 to 40%, raising the need for further research. In this regard, investigating the occurrence of structural variants, especially copy number variants, may be crucial. Based on these considerations, this review aims to provide an overview of copy number variants identified in cardiomyopathies and discuss them, considering diagnostic yield. This review will ultimately address the necessity of incorporating copy number variants into routine genetic testing for cardiomyopathies and channelopathies, a process increasingly enabled by advances in next-generation sequencing technologies. Full article

We report two cases of prolonged “unexpected” asystoles in patients with a wearable cardioverter-defibrillator (WCD) and a subcutaneous implantable cardioverter-defibrillator (ICD), respectively, which were promptly recognized and successfully managed. As these devices are designed to recognize and treat malignant tachyarrhythmias but do not provide pacing capabilities, it is crucial to identify patients with paroxysmal conduction disorders who might require backup pacing. For this reason, it is also important to leverage the monitoring features of both devices and their ability to detect the occurrence of bradyarrhythmias. Full article

Atherosclerotic cardiovascular disease (ASCVD) remains the leading global cause of morbidity and mortality, even in the era of aggressive low-density lipoprotein cholesterol (LDL-C) lowering. This persistent residual risk has prompted a reevaluation of atherogenic lipid markers, with non-high-density lipoprotein cholesterol (non-HDL-C) and apolipoprotein B (Apo B) emerging as superior indicators of the total atherogenic particle burden. Unlike LDL-C, non-HDL-C includes cholesterol from all atherogenic lipoproteins, while Apo B reflects the total number of atherogenic particles regardless of cholesterol content. Their clinical relevance is underscored in populations with diabetes, obesity, and hypertriglyceridemia, where LDL-C may not adequately reflect cardiovascular risk. This review explores the biological, clinical, and genetic foundations of non-HDL-C and Apo B as critical tools for risk stratification and therapeutic targeting. It highlights discordance analysis, inflammatory mechanisms in atherogenesis, the influence of metabolic syndromes, and their utility in specific populations, including those with chronic kidney disease and children with familial hypercholesterolemia. Additionally, the role of lipoprotein (a), glycation in diabetes, and hypertriglyceridemia are examined as contributors to residual risk. Clinical trials and genetic studies support Apo B and non-HDL-C as more robust predictors of cardiovascular events than LDL-C. Current guidelines increasingly endorse these markers as secondary or even preferred targets in complex lipid disorders. The incorporation of Apo B and non-HDL-C into routine clinical practice, especially for patients with residual risk, represents a paradigm shift toward personalized cardiovascular prevention. The review concludes with recommendations for guideline integration, emerging therapies, and future directions in biomarker-driven cardiovascular risk management. Full article

Aortic stenosis (AS), the most common valvular heart disease, is traditionally graded based on several echocardiographic quantitative parameters, such as aortic valve area (AVA), mean pressure gradient (MPG), and peak jet velocity (Vmax). This systematic review evaluates the clinical significance and prognostic implications of discordant high-gradient AS (DHG-AS), a distinct hemodynamic phenotype characterized by elevated MPG despite a preserved AVA (>1.0 cm²). Although often overlooked, DHG-AS presents unique diagnostic and therapeutic challenges, as high gradients remain a strong predictor of adverse outcomes despite moderately reduced AVA. Sixty-three studies were included following rigorous selection and quality assessment of the key studies. Prognostic outcomes across five key studies were discrepant: some showed better survival in DHG-AS compared to concordant high-gradient AS (CHG-AS), while others reported similar or worse outcomes. For instance, a retrospective observational study including 3209 patients with AS found higher mortality in CHG-AS (unadjusted HR: 1.4; 95% CI: 1.1 to 1.7), whereas another retrospective multicenter study including 2724 patients with AS observed worse outcomes in DHG-AS (adjusted HR: 1.59; 95% CI: 1.04 to 2.56). These discrepancies may stem from delays in intervention or heterogeneity in study populations. Despite the diagnostic ambiguity, the presence of high gradients warrants careful evaluation, aggressive risk stratification, and timely management. Current guidelines recommend a multimodal approach combining echocardiography, computed tomography (CT) calcium scoring, transesophageal echocardiography (TEE) planimetry, and, when needed, catheterization. Anatomic AVA assessment by TEE, CT, and cardiac magnetic resonance imaging (CMR) can improve diagnostic accuracy by directly visualizing valve morphology and planimetry-based AVA, helping to clarify the true severity in discordant cases. However, these modalities are limited by factors such as image quality (especially with TEE), radiation exposure and contrast use (in CT), and availability or contraindications (in CMR). Management remains largely based on CHG-AS protocols, with intervention primarily guided by transvalvular gradient and symptom burden. The variability among the different guidelines in defining severity and therapeutic thresholds highlights the need for tailored approaches in DHG-AS. DHG-AS is clinically relevant and associated with substantial prognostic uncertainty. Timely recognition and individualized treatment could improve outcomes in this complex subgroup. Full article

Background: In recent decades, aortic valve surgery has transitioned from conventional median sternotomy (MS) to minimally invasive techniques, including partial upper mini-sternotomy (PUMS) and right anterolateral mini-thoracotomy (RAMT). This study retrospectively compares the outcomes of aortic valve replacement (AVR) using PUMS during the learning phase with those of standard MS. Methods: A retrospective analysis was conducted on patients (n = 211) who underwent AVR for aortic stenosis. They were divided into MS (n = 119) and PUMS (n = 92) groups. Various preoperative, surgical and postoperative parameters, including survival, were examined. Results: Preoperatively, the main difference was age, with PUMS patients being older (67.5 ± 7 vs. 66.5 ± 9.6; p = 0.010). PUMS patients also had longer cardiopulmonary bypass (CPB) and cross-clamping times (99 ± 25 vs. 80 ± 16 min; p < 0.002; 79 ± 18 vs. 65 ± 13 min; p < 0.024). There were no significant differences in body mass index, prosthesis size, indexed effective orifice area, hospitalisation duration or any other monitored parameter. Echocardiographic follow-up found no differences in prosthetic pressure gradients, flow velocity or paravalvular leak between the PUMS and MS groups. Survival rates were similar over 1000 days. Conclusions: The data suggest that PUMS offers comparable surgical outcomes to MS for AVR with additional cosmetic benefits, undeterred by a learning curve. Full article

Background/Objectives: Patients with peripheral artery disease (PAD) have a heightened risk of major adverse cardiovascular events (MACE), including myocardial infarction, stroke, and death. Despite this, limited progress has been made in identifying reliable biomarkers to prognosticate such outcomes. Circulating growth factors, known to influence endothelial function and the progression of atherosclerosis, may hold prognostic value in this context. The objective of this research was to evaluate a broad range of blood-based growth factors to investigate their potential as predictors of MACE in patients diagnosed with PAD. Methods: A total of 465 patients with PAD were enrolled in a prospective cohort study. Baseline plasma levels of five different growth factors were measured, and participants were monitored over a two-year period. The primary outcome was the occurrence of MACE within those two years. Comparative analysis of protein levels between patients who did and did not experience MACE was performed using the Mann–Whitney U test. To assess the individual prognostic significance of each protein for predicting MACE within two years, Cox proportional hazards regression was performed, adjusting for clinical and demographic factors including a history of coronary and cerebrovascular disease. Subgroup analysis was performed to assess the prognostic value of these proteins in females, who may be at higher risk of PAD-related adverse events. Net reclassification improvement (NRI), integrated discrimination improvement (IDI), and area under the receiver operating characteristic curve (AUROC) were calculated to assess the added value of significant biomarkers to model performance for predicting 2-year MACE when compared to using demographic/clinical features alone. Kaplan–Meier curves stratified by IGFBP-1 tertiles compared using log-rank tests and Cox proportional hazards analysis were used to assess 2-year MACE risk trajectory based on plasma protein levels. Results: The average participant age was 71 years (SD 10); 31.1% were female and 47.2% had diabetes. By the end of the two-year follow-up, 18.1% (n = 84) had experienced MACE. Of all proteins studied, only insulin-like growth factor-binding protein 1 (IGFBP-1) showed a significant elevation among patients who suffered MACE versus those who remained event-free (20.66 [SD 3.91] vs. 13.94 [SD 3.80] pg/mL; p = 0.012). IGFBP-1 remained a significant independent predictor of 2-year MACE occurrence in the multivariable Cox analysis (adjusted hazard ratio [HR] 1.57, 95% CI 1.21–1.97; p = 0.012). Subgroup analyses revealed that IGFBP-1 was significantly associated with 2-year MACE occurrence in both females (adjusted HR 1.52, 95% CI 1.16–1.97; p = 0.015) and males (adjusted HR 1.04, 95% CI 1.02–1.22; p = 0.045). Incorporating IGFBP-1 into the clinical risk prediction model significantly enhanced its predictive performance, with an increase in the AUROC from 0.73 (95% CI 0.71–0.75) to 0.79 (95% CI 0.77–0.81; p = 0.01), an NRI of 0.21 (95% CI 0.07–0.36; p = 0.014), and an IDI of 0.041 (95% CI 0.015–0.066; p = 0.008), highlighting the prognostic value of IGFBP-1. Kaplan–Meier analysis showed an increase in the cumulative incidence of 2-year MACE across IGFBP-1 tertiles. Patients in the highest IGFBP-1 tertile experienced a significantly higher event rate compared to those in the lowest tertile (log-rank p = 0.008). In the Cox proportional hazards analysis, the highest tertile of IGFBP-1 was associated with increased 2-year MACE risk compared to the lowest tertile (adjusted HR 1.81; 95% CI: 1.31–2.65; p = 0.001). Conclusions: Among the growth factors analyzed, IGFBP-1 emerged as the sole biomarker independently linked to the development of MACE over a two-year span in both female and male PAD patients. The addition of IGFBP-1 to clinical features significantly improved model predictive performance for 2-year MACE. Measuring IGFBP-1 levels may enhance risk stratification and guide the intensity of therapeutic interventions and referrals to cardiovascular specialists, ultimately supporting more personalized and effective management strategies for patients with PAD to reduce systemic vascular risk. Full article

Bradyarrhythmia is associated with an increased risk of falls, syncope, and sudden cardiac arrest in Parkinson’s disease (PD). However, studies investigating bradyarrhythmia in PA have been scarce. Therefore, we aimed to assess trends, prevalence, and risk factors of bradyarrhythmia and pacemaker implantation in PD patients. The National Inpatient Sample was utilized to identify patients’ data with primary and secondary diagnoses of Parkinson’s disease (PD) from 2016 to 2020. A total of 333,242 patients had a PD diagnosis; of these, 5092 (1.5%) had comorbid diagnoses of bradyarrhythmia. The prevalence of bradyarrhythmia in patients with PD was 351.9 per 10,000 hospitalizations (3.5%), with an increase from 291.9 to 463.8 per 10,000. However, the trends remained relatively stable. The overall prevalence of pacemaker implantation in patients with PD was 79.9 per 10,000 hospitalizations (0.8%). The overall trend of pacemaker implantation was stable in patients with PD. Age ≥ 65, male sex, and comorbidities (atrial fibrillation, coronary artery disease, heart failure, hypertension, liver failure, obesity, peripheral vascular disease, renal failure) were associated with a higher likelihood of bradyarrhythmia in patients with PD. This study’s findings revealed an increase in the prevalence of bradyarrhythmia. However, the prevalence of pacemaker implantation remained relatively stable over the study period. Full article

Advancements in endovascular stent graft design have enabled the treatment of distal aortic arch pathologies. However, the length of the proximal landing zone remains a limitation, especially with vascular anomalies like an aberrant right subclavian artery (ARSA) posing additional challenges. A 78-year-old patient underwent computed tomography angiography (CTA), which revealed progressive enlargement of a distal aortic arch aneurysm located beyond an ARSA that coursed between the esophagus and trachea. Following evaluation by the multidisciplinary Aortic Team, a hybrid procedure was planned. A right carotid-to-ARSA bypass was performed and a Castor single-branched stent graft (CSBSG) was deployed in the aortic arch with its side branch directed into the left subclavian artery (LSA), thereby covering the origin of the ARSA. To prevent a type II endoleak, plug embolization of the ARSA origin was subsequently performed. CSBSG is a feasible treatment for distal aortic arch aneurysms, even in the presence of vascular anomalies such as ARSA. Full article

Background: Left ventricular filling pressure (LVFP) is pivotal in heart failure management, yet non-invasive assessment remains challenging. While echocardiography is the first line, cardiovascular magnetic resonance (CMR) offers enhanced accuracy. This study evaluates the interplay between CMR-derived LVFP and echocardiography, focusing on sex differences and correlations with N-terminal pro-brain natriuretic peptide (NT-proBNP). Methods: In this prospective study, 222 patients with CMR-derived LVFP > 14 mmHg underwent transthoracic echocardiography (TTE) and CMR. Sex-specific CMR equations (incorporating left atrial volume and ventricular mass) were used to estimate pulmonary capillary wedge pressure (PCWP). Correlations between imaging parameters and NT-proBNP were assessed. Results: CMR-derived LVFP showed no sex-based differences (p = 0.3143), unlike echocardiographic indices: women had higher E/e′ (p < 0.0001) and lower lateral mitral annular velocities (p = 0.0159). CMR-derived LVFP correlated strongly with NT-proBNP (r = 0.47, p < 0.0001), outperforming E/e′ (r = 0.41). Stratification by CMR PCWP tertiles revealed higher NT-proBNP (p = 0.0003), left atrial volumes (p < 0.0001), and septal thickness (p < 0.0001) in the highest tertiles. CMR-derived LVFP demonstrated superior diagnostic accuracy (AUC = 0.754 vs. 0.740 for E/e′) in identifying elevated NT-proBNP (>400 pg/mL). Sex-independent CMR measures contrasted with echocardiography, where parameters like left atrial volume varied by sex (p = 0.012). Conclusions: CMR-derived LVFP is a robust, sex-independent biomarker strongly linked to NT-proBNP, offering superior diagnostic performance over echocardiography. Its integration with echocardiographic indices enhances the non-invasive assessment of cardiac filling pressures, advocating a synergistic imaging approach to refine heart failure management. Full article

Cardiac allograft vasculopathy (CAV) is a leading cause of allograft dysfunction and failure. CAV prevention, early detection, and management are essential to increasing allograft survival. In this comprehensive review, we discuss various invasive and non-invasive modalities that are being utilized for CAV detection. Invasive coronary angiography provides a visualization of vascular anatomy but is limited in detecting the microvasculature and diffuse and early structural changes. The addition of intracoronary assessment techniques, including intravascular ultrasound, optical coherence tomography, and coronary flow reserve assessment, offer(s) superior sensitivity in identifying CAV. Non-invasive imaging modalities, such as cardiac magnetic resonance imaging, computed tomography angiography, and positron emission tomography, provide complementary insights into CAV with myocardial perfusion and allograft function while reducing procedural risks. Our aim is to guide clinicians in selecting appropriate imaging strategies tailored to individual recipients, to improve detection, monitoring, and outcomes in CAV. Full article

Background and Aim: Floating aortic thrombi are rare but potentially life-threatening entities, associated with a high risk of systemic embolization and subsequent complications such as ischemic stroke or mesenteric infarction. Therapeutic strategies range from urgent surgical intervention to conservative medical management with anticoagulation, depending on the patient’s clinical status and thrombus morphology. This report presents two cases of floating aortic thrombi managed with distinct approaches, surgical and medical, underscoring the importance of individualized treatment guided by embolic risk and comorbidities. Patients and Methods: The first case involves a 59-year-old male presenting with abdominal pain and emesis. Imaging confirmed mesenteric ischemia, necessitating emergent laparotomy and extensive jejunal resection. Postoperative imaging identified a mobile thrombus at the ascending aorta–aortic arch junction, with evidence of cerebral embolism. The patient underwent urgent surgical thrombectomy, ascending aortic resection, and hemiarch replacement. The second case describes an 88-year-old male who presented with bilateral upper limb paresthesia. Neuroimaging revealed acute supra- and infratentorial ischemic lesions suggestive of embolic stroke. A floating thrombus was identified in the ascending aorta, with an additional thrombus in the descending thoracic aorta. Given the patient’s advanced age, comorbid conditions, and thrombus stability, a conservative approach with systemic anticoagulation and close radiologic surveillance was chosen. Conclusions: These cases illustrate the need for tailored management of floating aortic thrombi. While surgical resection remains indicated in unstable or high-risk embolic cases, anticoagulation may suffice for stable lesions in patients with elevated surgical risk. Further studies are needed to establish standardized therapeutic guidelines. Full article

The imbalance in the interaction between the autonomic nervous system and the immune system serves as a central mechanism in the onset and progression of cardiovascular diseases. The excessive activation of the sympathetic nervous system and suppression of vagal function contribute to chronic inflammation and cardiac remodeling. Precision medicine, by integrating multidimensional data such as genomics and metabolomics, offers a novel perspective for the personalized design of exercise interventions. This systematic review explores the bidirectional regulatory mechanisms of exercise interventions on the autonomic nervous system–immune axis and examines the potential applications of precision medicine in optimizing exercise prescriptions and clinical translation. Exercise significantly improves cardiovascular function through immunometabolic reprogramming, which includes suppressing sympathetic overactivity, enhancing vagal tone, and modulating the IL-6/IL-10 balance, as well as activating the short-chain fatty acid (SCFA)–Treg axis. Moreover, precision-medicine-driven ACE I/D gene typing provides a basis for selecting tailored exercise prescriptions, thereby significantly enhancing the efficacy of exercise interventions. By leveraging a multi-tiered “neuro–immune–metabolic” regulatory framework, exercise interventions contribute to improved cardiovascular health. The application of precision medicine technology overcomes individual variability constraints, advancing exercise prescription design from generalized recommendations toward personalized and dynamically adaptive strategies. Full article

Background: Pneumopericardium is the presence of air within the pericardial cavity. We report a case of iatrogenic pneumopericardium following pericardiocentesis in a patient with primary cardiac angiosarcoma. Additionally, we provide a systematic review of pericardiocentesis-associated pneumopericardium to offer a comprehensive overview and evaluate the role of echocardiography in its diagnosis. Methods: The PubMed database was searched from inception until January 2025 to perform a systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to evaluate articles on iatrogenic pneumopericardium following pericardiocentesis published in the English language. The Joanna Briggs Institute (JBI) Critical Appraisal Checklist for Case Reports was used to appraise the included case reports. Results: Of the 108 search results obtained, after screening and a backward citation search, 37 articles were selected for inclusion in this review, accounting for a total of 37 patients. According to the JBI Critical Appraisal Checklist for Case Reports, 7 case reports were of high quality and 12 of low quality. The overall evidence of quality of the case reports was moderate, and 51.6% of patients developed hemodynamic compromise or showed signs of cardiac tamponade. The main underlying cause for the development of pneumopericardium was issues relating to the catheter drainage system; 64.9% of cases required decompressive therapy. Conclusions: Pneumopericardium can occur as a complication after pericardiocentesis and must therefore be considered in symptomatic patients. While detection by transthoracic echocardiography is difficult and relies on non-validated signs, chest X-ray and computed tomography can provide a definitive diagnosis. Full article

The anatomical arrangement of the atrioventricular node has been likened to a riddle wrapped up in an enigma. There are several reasons for this alleged mystery, not least the marked variability in structure between different species. Lack of detailed knowledge of the location of the node relative to the atrial and ventricular septal structures has also contributed to previous misunderstandings. Recent studies comparing the findings of gross dissection with virtual dissection of living datasets, combined with access to a large number of serially sectioned human and animal hearts, have served to provide the evidence to solve the riddle. We summarise these findings in this review. We explain how the node is located within the atrial walls of the inferior pyramidal space. It becomes the non-branching component of the atrioventricular conduction axis as the axis extends through the plane of atrioventricular insulation to enter the infero-septal recess of the left ventricular outflow tract. The node itself is formed by contributions from the tricuspid and mitral vestibules, with extensive additional inputs from the base of the atrial septum. We show how knowledge of development enhances the appreciation of the arrangements and offers an explanation as to why, on occasion, there can be persisting nodoventricular connections. We discuss the findings relative to the circuits producing atrioventricular re-entry tachycardia. We conclude by emphasising the significance of the variation of the anatomical arrangements within different mammalian species. Full article

Obesity has been shown to be an independent risk factor for the development of heart failure (HF) and atherosclerotic cardiovascular disease. Here, we tried to analyze the distribution of obesity by age and sex in a 10-year sample cohort of newly diagnosed HF patients in Korea. A total of 35,869 patients newly diagnosed with HF between 2006 and 2015 from a nationally representative random sample of 1,000,000 people were included in this study. The data of age and sex for each subgroup according to body mass index were analyzed and compared with the general population. The obese group accounted for 43.3% of the total, and the frequency of obese patients was the highest among those in their 60s (4561). The proportion of obesity was the highest among those in their 40s (57.7%) and 30s (57.3%) in men and the highest among those in their 60s (52.2%) in women. The underweight group increases with age in both men and women, and the proportion of the high-aged group over 80 years old in the underweight group of women is significantly much higher than that of men. Conclusively, the proportion of obesity is higher than in the general population in HF patients. Obesity patterns analyzed by age were different for each sex. Full article

Although chronic total occlusions (CTO) are a common finding in patients treated with coronary artery bypass grafting (CABG), it is still not clear how their presence impacts the long-term outcomes achieved with surgery. We aimed to investigate the impact of CTO on the long-term results of patients with coronary artery disease who underwent CABG. Patients from 2005 to 2023 operated on at the University Hospital Freiburg-Bad Krozingen were analyzed. The primary outcome was all-cause mortality after 3-, 5-, and 10 years. The secondary outcome was the need for coronary reintervention in the follow-up period. Propensity score matching and multivariable Cox regression were performed, and Kaplan–Meier curves were used to graphically display the outcomes for the two groups. Of the 3424 patients included in the analysis, 1784 (52%) were categorized as CTO and 1640 (48%) were categorized as no-CTO. After propensity scoring, 1232 pairs were successfully matched. The 3-, 5-, and 10-year all-cause mortality was significantly higher in patients with CTO (p = 0.028; p < 0.001; p < 0.001). The need for coronary reintervention after 3-, 5-, and 10 years was comparable in both groups. In addition, multivariable Cox Regression showed that CTO presence (HR 1.220, 95% CI 1.047–1.420, p = 0.010) was an independent predictor of 10-year mortality. Full article

Objective: We aimed to evaluate the feasibility, added value, and radiation dose of coronary computed tomography angiography (CCTA) and stress dynamic CT myocardial perfusion imaging (MPI) in patients with coronary artery disease (CAD) in a real-world setting. Materials and Methods: This retrospective study included 65 patients (mean age: 51.2 ± 11.5 years; 21 female) with moderate CAD, selected from the Radiological Database of our hospital between May 2022 and December 2024. All patients underwent CCTA and stress dynamic CT-MPI using a third-generation dual-source CT scanner. The shuttle-mode acquisition technique was used for CT-MPI with 60 mL of contrast (iopamidol, 370 mg iodine/mL) administered at a flow rate of 6 mL/s. The mean myocardial blood flow (MBF) and other quantitative parameters were measured for both CAD and reference segments (RSs). A 17-segment-based analysis was employed (excluding the apex). The MBF ratio, defined as the mean MBF value of CAD segments divided by that of RS, was used with a cut-off value of 0.85 to distinguish hypoperfused from non-hypoperfused segments within CAD territories. Non-parametric statistical tests were applied. Results: A total of 1040 segments were evaluated. In 62 segments, the mean MBF of CAD territories was found to have decreased. The mean MBF and myocardial blood volume (MBV) in hypoperfused CAD segments were 65.1 ± 19.8 mL/100 mL/min and 14.5 ± 2.7 mL/100 mL, respectively, both significantly lower compared to non-hypoperfused CAD segments and RSs (p < 0.001). The mean effective dose of the protocol was 6.3 ± 1.4 mSv, corresponding to an estimated individual lifetime cancer risk of approximately 0.06% per test, based on BEIR VII Phase 2 modeling. This risk is cumulative, with repeat testing over a 10-year period potentially increasing lifetime cancer risk in proportion to total radiation exposure. The mean total examination time was 26 ± 4 min. Conclusion: The combined CCTA and dynamic CT-MPI protocol is feasible in real-world clinical practice and offers a comprehensive morphological and functional assessment of moderate CAD, with a manageable radiation dose and examination time. Full article

Right heart failure is a condition where the right ventricle fails to pump blood into the pulmonary artery, and, in turn, the lungs. This condition frequently presents after the implantation of a left ventricular assist device (LVAD). Ventricular assist candidates who have LVADs implanted possess various pathophysiological and cardiovascular features that contribute to the later development of RHF. With LVADs serving as bridge-to-transplantation, bridge-to-candidacy, and destination therapies, it is imperative that the pre-operative indicators of RHF are identified and assessed. Multiple predictive models and parameters have been developed to quantify the risk of post-LVAD right heart failure. Clinical, laboratory, hemodynamic, and echocardiographic parameters have all been used to develop these predictive approaches. RHF remains a major cause of morbidity and mortality after LVAD implantation. Predicting RHF helps clinicians assess treatment options, including biventricular support or avoiding high-risk surgery. In our review, we noted the varying definitions for RHF in recent models, which affected respective predictive accuracies. The pulmonary arterial pulsatile index (PAPi) and right ventricular longitudinal strain parameters were noted for their potential to enhance current models incrementally. Meanwhile, mechanistic and machine learning approaches present a more fundamental shift in the approach to making progress in this field. Full article

Objectives: Several conditions associated with type A aortic dissection may require preoperative invasive mechanical ventilation (IMV). The current literature lacks data on this subset of patients’ prevalence and postoperative outcomes. This study aims to investigate this unexplored issue in a multicenter European registry. Methods: Data from 3735 patients included in the European Registry of Type A Aortic Dissection (ERTAAD) were the subject of this analysis. Bootstrapped Least Absolute Shrinkage and Selection Operator (LASSO) logistic regression was performed for variable selection to identify key predictors of hospital death. In the second step, a multilevel multivariable logistic regression (MMLR) was carried out, given the clustered structure of the data. Results: A total of 346 (9.3%) out of 3735 patients required preoperative IMV. Compared to the non-IMV patients, patients requiring IMV had a significantly higher rate of organ malperfusion (52% vs. 35%, p < 0.001) and a higher proportion of tears in the aortic root (p = 0.048). The in-hospital mortality rate among IMV patients was 38% vs. 15% in non-IMV patients (p < 0.001), without a difference in post-discharge survival (p = 0.84). At the MMLR, patients who required IMV had 135% higher odds of in-hospital death compared to the remaining patients. IMV yielded the second highest odds in the prediction model for in-hospital mortality (OR 2.13, CI 1.60 to 2.85, p < 0.001). Among IMV patients, the extension of surgery to the aortic arch was significantly associated with increased in-hospital mortality (p < 0.001, OR 2.98). In multivariable analysis, preoperative IMV was independently associated with increased odds of in-hospital mortality. Conclusions: The need for invasive mechanical ventilation before surgical repair for type A aortic dissection is not infrequent. In this subpopulation, the in-hospital mortality rate was twofold compared to patients who did not require IMV. The awareness of the preoperative risk profile and outcomes of this subset of patients should urge surgeons to tailor the surgical strategy more appropriately to improve the immediate postoperative results. Full article