Search Results (260)

Background and Objectives: Effective myocardial protection is essential for successful cardiac surgery outcomes, especially in complex and prolonged procedures. To this end, Del Nido (DN) and histidine-tryptophan-ketoglutarate (HTK) cardioplegia solutions are widely used; however, their comparative efficacy in adult surgeries with prolonged aortic cross-clamp (ACC) times remains unclear. This study aimed to compare the efficacy and safety of DN and HTK for myocardial protection during prolonged ACC times in adult cardiac surgery and to define clinically relevant thresholds. Materials and Methods: This retrospective study included a total of 320 adult patients who underwent cardiac surgery under cardiopulmonary bypass (CPB) with an aortic cross-clamp time ≥ 90 min. Data were collected from the medical records of elective adult cardiac surgery cases performed at a single center between 2019 and 2025. Patients were categorized into two groups based on the type of cardioplegia received: Del Nido (n = 160) and HTK (n = 160). The groups were compared using 1:1 propensity score matching. Clinical and biochemical outcomes—including troponin I (TnI), CK-MB, lactate levels, incidence of low cardiac output syndrome (LCOS), and need for mechanical circulatory support—were analyzed between the two cardioplegia groups. Subgroup analyses were performed according to ACC duration (90–120, 120–150, 150–180 and >180 min). The predictive threshold of ACC duration for each complication was determined by ROC analysis, followed by the analysis of independent predictors of each endpoint by multivariate logistic regression. Results: Intraoperative cardioplegia volume and transfusion requirements were lower in the DN group (p < 0.05). HTK was associated with lower TnI levels and less intra-aortic balloon pump (IABP) requirement at ACC times exceeding 180 min. Markers of myocardial injury were lower in patients with an ACC duration of 120–150 min in favor of HTK. The propensity for ventricular fibrillation after ACC was significantly lower in the DN group. Significantly lower postoperative sodium levels were observed in the HTK group. Prolonged ACC duration was an independent risk factor for LCOS (odds ratio [OR]: 1.023, p < 0.001), VIS > 15 (OR, 1.015; p < 0.001), IABP requirement (OR: 1.020, p = 0.002), and early mortality (OR: 1.016, p = 0.048). Postoperative ejection fraction (EF), troponin I, and CK-MB levels were associated with the development of LCOS and a VIS > 15. Furthermore, according to ROC analysis, HTK cardioplegia was able to tolerate ACC for up to a longer duration in terms of certain complications, suggesting a higher physiological tolerance to ischemia. Conclusions: ACC duration is a strong predictor of major adverse outcomes in adult cardiac surgeries. Although DN cardioplegia is effective and economically advantageous for shorter procedures, HTK may provide superior myocardial protection in operations with long ACC duration. This study supports the need to individualize cardioplegia choice according to ACC duration. Further prospective studies are needed to establish standard dosing protocols and to optimize cardioplegia selection according to surgical duration and complexity. Full article

Background/Objectives: High-risk percutaneous coronary interventions (HR-PCIs) often require mechanical circulatory support (MCS) to maintain hemodynamic stability. Intra-aortic balloon pump (IABP) and percutaneous left ventricular assist device (PLVAD) are two commonly used MCS devices that differ in their mechanisms. We aimed to evaluate and compare the clinical outcomes associated with IABP and PLVAD use in HR-PCIs without cardiogenic shock. Methods: We conducted a search of PubMed, Scopus, Cochrane, Mendeley, Web of Science, and Embase to identify relevant randomized controlled trials and cohort studies, and we included 13 studies for the systematic review and meta-analysis. The primary goal was to define the difference in early mortality (in-hospital and 30-day mortality), major bleeding, and major adverse cardiovascular event (MACE) components (cardiogenic shock, acute kidney injury (AKI), and stroke/TIA) in IABP and PLVAD. We used a random-effects model with the Mantel–Haenszel statistical method to estimate odds ratios (ORs) and 95% confidence intervals. Results: Among 1 trial and 12 cohort studies (35,554 patients; 30,351 IABP and 5203 PLVAD), HR-PCI with IABP was associated with a higher risk of early mortality (OR = 1.53, 95% CI [1.21, 1.94]) and cardiogenic shock (OR = 2.56, 95% CI [1.98, 3.33]) when compared to PLVAD. No significant differences were found in the rates of arrhythmia, major bleeding, AKI, stroke/TIA, or hospital length of stay. Conclusions: In high-risk PCIs, PLVAD use is associated with lower early mortality and cardiogenic shock risk compared to IABP, with no significant differences in other major outcomes. Full article

p-Cresyl sulfate (PCS), a gut-derived uremic toxin with proinflammatory and cytotoxic effects, has been implicated in cardiovascular injuries among patients with chronic kidney disease (CKD). Aortic stiffness (AS), assessed by carotid–femoral pulse wave velocity (cfPWV), is a recognized predictor of cardiovascular risk. This study investigated the association between serum PCS levels and AS in patients with nondialysis-dependent CKD. In total, 165 patients with nondialysis-dependent CKD were enrolled. Clinical data and fasting blood samples were collected. Arterial stiffness (AS) was assessed bilaterally by measuring carotid–femoral pulse wave velocity (cfPWV) on both the left and right sides. A value above 10 m/s was considered indicative of increased stiffness. Serum PCS levels were quantified using high-performance liquid chromatography–mass spectrometry. Fifty patients (30.3%) had AS. The AS group was significantly older and had higher diabetes prevalence, systolic blood pressure, fasting glucose, urinary protein-creatinine ratio, and PCS levels than the control group. In the multivariate analysis, both PCS (odds ratio [OR]: 1.097; 95% confidence interval [CI]: 1.024–1.175; p = 0.008) and age (OR: 1.057; 95% CI: 1.025–1.090; p < 0.001) were independently associated with AS. In conclusion, elevated serum PCS and older age were independently associated with AS. Thus, PCS is a potential early marker of vascular damage in CKD. Full article

The use of temporary mechanical circulatory support in refractory heart failure cardiogenic shock (HFCS) has risen, leading to potential complications. Post-Cardiac Injury Syndrome (PCIS) from Impella insertion is rare but may result from subclavian artery manipulation and aortic irritation. We report the first case of pericarditis (PCIS) caused by Impella 5.5 insertion in an HFCS patient awaiting heart transplantation. The patient developed chest pain, tachycardia, and hypotension post-Impella insertion. Laboratory results and electrocardiograms confirmed PCIS. Treatment with Ibuprofen and Colchicine was successful. He received a heart transplant 14 days later. This case emphasizes recognizing iatrogenic pericarditis after Impella insertion and the need to avoid additional myocardial strain. Full article

Nicotine-induced oxidative stress contributes significantly to vascular endothelial dysfunction. While negative air ions (NAIs) demonstrate potential blood-pressure-regulating and antioxidant properties, their mechanistic role remains unclear. This study examined the effects of NAIs against nicotine-induced oxidative damage and vascular endothelial injury in spontaneously hypertensive rats (SHRs). Western blotting was used to detect the expression levels of the α7nAChR/MAPK/AP1 pathway. Transcriptomic sequencing was performed to identify the differentially expressed genes after treatment with nicotine or NAIs. Furthermore, reactive oxygen species (ROS), endothelin-1 (ET-1), and [Ca²⁺]_i levels were detected in human aortic endothelial cells (HAECs) treated with nicotine, and the relationship between transcription factor activator protein 1 (AP1) and the target genes was further elucidated through ChIP–qPCR. Nicotine exposure in SHRs elevated blood pressure and induced oxidative damage through α7nAChR/MAPK/AP1 pathway activation, causing endothelial structural disruption. These effects manifested as decreased NO/eNOS and increased ET-1/ET_ab expression, while these changes were reversed by NAIs. In HAECs, nicotine impaired proliferation while increasing oxidative stress and [Ca²⁺]_i levels. This endothelial damage was markedly attenuated by either NAIs or fibronectin 1 (Fn1)/secreted phosphoprotein 1 (Spp1) knockdown. Mechanistically, we identified AP1 as the transcriptional regulator of FN1 and SPP1. NAIs attenuate nicotine-induced endothelial dysfunction in hypertension by inhibiting AP1-mediated FN1 and SPP1 activation, providing novel insights for smoking-associated cardiovascular risk. Full article

Background/Objectives: Apolipoprotein E receptor-2 (apoER2) exists in various alternatively spliced forms, including variants that express apoER2 with or without exon 19 in the cytoplasmic domain. This study compared vascular response to endothelial denudation, as well as diet-induced atherosclerotic and metabolic diseases, between genetically modified mice that exclusively expressed the apoER2 splice variant with or without exon 19 to determine the impact of apoER2 exon 19 motif in cardiometabolic disease modulation. Methods: Vascular response to injury was assessed by measuring neointima area of the carotid arteries after endothelial denudation. The genetically modified mice were also fed a high-fat high-cholesterol diet for 16 weeks for the determination of body weight gain, glucose and insulin levels, glucose tolerance and insulin secretion. Additionally, adipose tissue inflammation was assessed by analysis of adipose gene expression, and atherosclerosis was characterized by measuring fatty lesion size in the whole aorta, as well as in the aortic roots. Results: The results showed that whereas the expression of either splice variant is sufficient to impede denudation-induced fibrotic neointima formation and complex necrotic atherosclerotic lesions, the expression of the apoER2 splice variant containing exon 19 is necessary for the complete protection of injury-induced neointima formation in the vessel wall. However, exclusive expression of either apoER2 cytoplasmic splice variant does not influence the early phase of atherogenesis. Additionally, the exclusive expression of apoER2 without exon 19 promotes adipocyte inflammation and accelerates diet-induced insulin resistance and glucose intolerance. Conclusions: These results indicate that the apoER2 cytoplasmic variants have distinct and cell type-specific roles in influencing cardiometabolic disease development. Full article

Background: Intra-aortic balloon pump (IABP) augments coronary perfusion during high-risk percutaneous coronary interventions (PCI). We sought to identify patients who benefited from prophylactic IABP (P-IABP) compared to rescue-IABP (R-IABP). Methods: All consecutive non-cardiogenic shock patients undergoing high-risk PCI with IABP support at Ulm University Hospital, Germany, between 2012 and 2020 were grouped based on the timing of IABP insertion in the pre-interventional P-IABP or peri-interventional R-IABP group. We compared the primary endpoint peri-interventional high-sensitivity Troponin T (hsTnT) increase, sought baseline characteristics associated with the endpoint in the R-IABP group, and compared their correlation strengths between the groups. Results: Interventional outcomes of 44 patients with P-IABP implantation were compared with those of 15 patients with R-IABP implantation. P-IABP was associated with a lower peri-interventional hsTnT increase (p = 0.008, r = 0.390). In the R-IABP group, the presence of ST-segment elevation (p = 0.037, r = 0.631), low systolic blood pressure (RRsyst) (p = 0.007, r = 0.893 (inverse correlation)), and elevated NT-proBNP levels (p < 0.001, r = 0.953) were associated with higher hsTnT increases. HsTnT increase was significantly smaller in the P-IABP group in patients with low RRsyst (IZI = 2.6) and high NT-proBNP levels (IZI = 3.36). Patients with RRsyst < 120 mmHg (p = 0.007) and NT-proBNP levels ≥ 900 pg/mL (Cohen’s d = 0.70, respectively 1.17 for ≥5000 pg/mL and 5.01 for ≥10,000 pg/mL) showed lower peri-interventional hsTnT increase when treated with P-IABP compared to R-IABP, while patients with NT-proBNP levels < 900 pg/mL showed a contrary effect (Cohen’s d = −0.90). Cox regression analysis showed that a high peri-interventional hsTnT increase was significantly associated with a shorter survival time (p = 0.046). Conclusions: P-IABP use in high-risk PCI was associated with reduced peri-interventional myocardial injury, as measured by lower hsTnT increase, which was associated with improved survival in patients with low systolic blood pressure and elevated NT-proBNP levels. Thus, these conditions should be considered for indicating P-IABP. Full article

Background/Objectives: Challenges in normothermic machine perfusion (NMP) remain, particularly concerning the duration for which individual organs can be safely preserved. We hypothesize that optimal preservation can be achieved by perfusing organs together in a multivisceral block. Therefore, our aim was to establish a platform for ex situ multivisceral organ perfusion. Methods: Multivisceral grafts containing the liver, kidneys, pancreas, spleen, and intestine were obtained from Yorkshire pigs. Three generation (gen) set-ups were tested during the iterative design process, and minor changes were made throughout. Gen 1 (n = 4) used a custom-designed single perfusion circuit. Gen 2 (n = 3) employed a dual perfusion circuit. Gen 3 (n = 4) featured a single perfusion circuit with an optimized basin and reservoir. Grafts underwent NMP using an autologous blood-based perfusate, while hemostatic parameters and function were assessed. Results: Comparing Gen 1 versus Gen 3, the mean aortic flow improved (1.018 vs. 2.089 L), resistance decreased (0.224 vs. 0.038), urine output increased (51.90 vs. 271.3 mL), oxygen consumption rose (43.56 vs. 49.52 mL O₂/min), perfusate lactate levels dropped (10.44 vs. 3.10 mmol/L), and the pH became more physiological (7.27 vs. 7.30). Cellular injury trended lower in Gen 3. Histological evaluation demonstrated minimal differences in Gens 2 and 3. Conclusions: We demonstrate the feasibility of abdominal multivisceral NMP for up to 8 h. Adequate arterial flow, stable perfusate pH, and high oxygen consumption in setup 3 indicated organ viability. Multivisceral perfusion may serve as a plat-form for long-term NMP. Full article

Background: Obstructive sleep apnea (OSA) is a prevalent but frequently underdiagnosed comorbidity in patients undergoing cardiac surgery, including coronary artery bypass grafting (CABG), aortic valve replacement (AVR), and mitral valve repair or replacement (MVR). This systematic review and meta-analytic synthesis investigates the relationship between OSA and postoperative morbidity and mortality, with particular attention to the predictive utility of established screening instruments. Methods: A systematic search of the PubMed database was conducted (April 2025), identifying 724 articles published in the last ten years. Seventeen primary studies met the inclusion criteria for qualitative synthesis, and four additional studies were included in the meta-analyses. Outcomes assessed included atrial fibrillation, major adverse cardiac and cerebrovascular events (MACCE), acute kidney injury (AKI), respiratory complications, pneumonia, hospital length of stay (LOS), and mortality. Risk of bias was assessed qualitatively based on study design and reporting limitations. This review was registered in the PROSPERO database under registration number CRD420251049574. Results: Meta-analyses demonstrated significantly elevated odds of atrial fibrillation (OR = 2.44, 95% CI: 1.46–4.07), major adverse cardiac and cerebrovascular events (OR = 2.06, 95% CI: 1.61–2.63), acute kidney injury (OR = 2.24, 95% CI: 1.67–3.01), and respiratory complications (OR = 1.15, 95% CI: 1.05–1.25) among patients with OSA. Additionally, OSA was associated with a significantly prolonged hospital length of stay (standardized mean difference [SMD] = 0.62, 95% CI: 0.46–0.78) and a marginal increase in pneumonia risk (OR = 1.07, 95% CI: 1.00–1.15). Evidence regarding stroke, intensive care unit (ICU) stay, and mortality was inconsistent or underpowered. Conclusions: Across core outcomes, findings were consistent across multiple studies involving a large patient population. Obstructive sleep apnea is a clinically consequential risk factor in cardiac surgery, associated with increased perioperative complications and prolonged hospitalization. These findings support the integration of routine OSA screening into preoperative risk assessment protocols. Further prospective, multicenter trials are warranted to assess the efficacy of perioperative management strategies, including continuous positive airway pressure (CPAP) therapy, in improving surgical outcomes. Full article

(1) Background: Vascular mural cells reside in the media and outer layers of the vessel wall. Their ability to proliferate and migrate or to change phenotype in response to external cues is a central feature of the vascular response to injury. Genetically engineered mice are used for loss- or gain-of-function analyses or lineage tracing in vivo, their primary cells for mechanistic studies in vitro. Whether and how cultivation conditions affect their phenotype and function is often overlooked. (2) Methods: Here, we systematically studied how the cultivation of primary mural cells isolated from the aorta of adult wild-type mice in either basal medium (DMEM) or special media formulated for the cultivation of fibroblasts or pericytes affects their phenotype and function. (3) Results: Medium composition did not alter cell viability, but the mRNA levels of differentiated smooth muscle cell markers were highest in vascular mural cells expanded in DMEM. Conversely, significantly higher numbers of proliferating and migrating cells were observed in cells expanded in Pericyte medium, and cytoskeletal rearrangements supported increased migratory capacities. Significantly reduced telomere lengths and metabolic reprogramming was observed in aortic mural cells cultured in Fibroblast medium. (4) Conclusions: Our findings underline the plasticity of primary aortic mural cells and highlight the importance of the culture media composition during their expansion, which could be exploited to interrogate their responsiveness to external stimuli or conditions observed in vivo or in patients. Full article

Background/Objectives: While the presence of inflammatory processes in stenotic aortic valves is acknowledged, no systematic characterization of the systemic immune reaction upon aortic valve stenosis (AS) has been performed yet. The hypothesis of this study was that AS induces a systemic inflammatory reaction linked with local processes in the heart. Methods: Murine wire injury (WI) to induce AS, or sham surgery, were performed prior to the 4-week assessment of AS severity, left ventricular (LV) function and hypertrophy with echocardiography (echo). Organ weights, levels of leukocytes, cytokines and costimulatory molecules in blood, heart, and peripheral immune organs (spleen, liver, lymph nodes), and immune cell uptake of Cy5-labelled perfluorocarbon nanoemulsions were measured. Results: Trends towards correlation were found between organ weights, myocardial immune cells and echo. Cytokine mRNA levels trended mainly towards an increase in heart and regional lymph nodes and a reduction in spleen and liver, and correlation with echo was more homogeneous after WI. Unchanged cytokine protein levels in myocardium and plasma trended to correlate with echo. A homogeneous pattern was found for echo and costimulatory molecule correlation, while PFC uptake by lymphatic cells was reduced upon AS. Conclusions: The results suggest a link between number and activation state of leukocytes in peripheral organs and cardiac processes in AS. Considering the pathological value of inflammation, it is crucial that future studies investigate if a modulation of the systemic inflammatory reaction relieves severity of AS and opposes development of heart failure. Full article

Background: Sprinting, a high-intensity, short-duration exercise, induces oxidative stress. This causes molecular and ultrastructural alterations. Antioxidant supplementation may mitigate side effects of near or complete exhaustion. Methods: Twenty-eight healthy male adult rats received orally normal saline, carboxymethylcellulose (vehicle), artificial, N-acetylcysteine or a natural antioxidant, Rutin. Rats were subjected to treadmill sprinting at increasing speeds for 5 days/week. After 26 days, samples were collected to measure oxidative stress (malondialdehyde, MDA; the ratio of reduced-to-oxidized glutathione, GSH/GSSG), inflammation markers (enzymatic level of inducible nitric oxide synthase, iNOS; cytokine level of tumor necrosis factor alpha, TNFα) and for transmission electron microscopy (TEM) analysis. Results: Rutin attenuated MDA levels and increased antioxidant protection in all tissues, while NAC decreased the lipid peroxidation in all tissues except the lungs. NAC increased aortic inflammation, with higher TNF-α and iNOS. Sprinting caused intimal detachment in the heart and aorta. Rutin and NAC minimized endocardium alterations. Additionally, Rutin prevented myocardial disorganization. Conclusions: Rutin mitigated the oxidative stress damage of sprinting in the heart, aorta, skeletal muscle and lung. NAC protected against oxidative injury caused by sprinting in the heart, aorta and muscle but not the lung, and it induced aortic inflammation. Full article

Aortic stenosis (AS) is a progressive valvular heart disease characterized by fibrocalcific remodeling, inflammation, and hemodynamic disturbances. Serum biomarkers may indirectly reflect these processes. Autotaxin (ATX) and lysophosphatidic acid (LPA) have been implicated in osteogenic differentiation of valvular interstitial cells, while growth differentiation factor-15 (GDF-15) reflects cellular stress and vascular changes. Thrombomodulin (TM) indicates endothelial injury and interacts with thrombin. This study aimed to evaluate biomarkers focusing on serum ATX, LPA, GDF-15, and TM levels and flow-mediated dilatation (FMD) in patients with AS. Overall, 149 patients were included in the study: 86 consecutive patients with AS hospitalized due to qualification for invasive treatment of AS and 63 controls. The clinical characteristics, echocardiographic data, FMD, and the following biomarkers—ATX, LPA, GDF-15, and TM—were included in the analysis. AS patients presented increased serum levels of ATX, GDF-15, and TM as compared to the controls. Differences in LPA levels were not statistically significant. FMD values were significantly lower in AS patients. The biomarkers mentioned above and FMD correlated with AS severity. There were no differences in both biomarkers’ serum levels and FMD regarding the hemodynamic AS phenotype. GDF-15 serum level was a risk factor for all-cause mortality and MACCE in the 12-month follow-up. Full article

Background: Aortic valve stenosis remains the most prevalent valvular pathology in Western countries. Rapid deployment bioprosthesis (RD) has emerged as a promising alternative to conventional valves for surgical aortic valve replacement (SAVR), particularly in elderly and high-risk patients. This study reports the short- and long-term outcomes of RD in patients with isolated aortic stenosis. Methods: A retrospective single-center analysis was conducted on 382 patients who underwent RD-AVR between 2014 and 2020. Data were collected from clinical files and national electronic databases. Primary outcomes included cardiopulmonary bypass (CPB) and cross-clamping (XC) times, postoperative complications, and long-term survival. Results: The mean age was 75.6 ± 5.9 years, with 29.8% of patients over 80 years old and a mean EuroSCORE II of 2.3 ± 1.5%. CPB and XC times were 36.7 ± 10.8 and 27.4 ± 8.1 min, respectively. Postoperative complications included acute kidney injury (AKI, 53.4%), de novo atrial fibrillation (31.9%), and high-grade/complete atrioventricular block with permanent pacemaker implantation (9.8%). In-hospital and 30-day mortality was 1.02% and 2.3%, respectively. The 5-year survival rate was 77%. At 6 months postoperatively, the mean transvalvular gradient was 11.1 ± 4.7 mmHg. At a median follow-up of 6.7 years, no cases of structural valve deterioration and only one case of endocarditis were reported. Conclusion: In this single-center study, RD in isolated AVR demonstrated favorable short- and long-term outcomes, including no structural valve deterioration at mid-term follow-up. These devices offer a safe and effective alternative to conventional SAVR, particularly in high-risk populations. Full article

Aortic stenosis (AS), the most prevalent valvular heart disease, is increasingly recognized as an active disease process driven by a convergence of hemodynamic stress, inflammation, oxidative injury, and metabolic remodeling. While transcatheter and surgical valve replacement remain the standard interventions for severe AS, they fail to reverse the chronic myocardial remodeling that underlies adverse outcomes in many patients. Sodium–glucose cotransporter 2 (SGLT2) inhibitors have emerged as promising cardioprotective agents, with effects extending well beyond glycemic control. Recent mechanistic studies reveal that SGLT2 is expressed in the myocardium of patients with AS and is linked to pathways of fibrosis, inflammation, and energetic dysfunction. Experimental models and translational data demonstrate that SGLT2 inhibition attenuates maladaptive remodeling through modulation of TGF-β, NF-κB, NLRP3 inflammasome, and oxidative stress signaling while enhancing mitochondrial energetics and endothelial function. Importantly, clinical evidence from randomized and real-world studies suggests that SGLT2 inhibitors improve heart failure outcomes following valve replacement and may slow AS progression. This review integrates current pathophysiological insights with emerging molecular and clinical data to delineate the therapeutic rationale for SGLT2 inhibition in AS. By targeting both myocardial and valvular components of the disease, SGLT2 inhibitors may offer a novel disease-modifying strategy with potential implications across the AS continuum—from asymptomatic stages to the post-interventional setting. Ongoing and future trials are warranted to define optimal patient selection, timing, and biomarkers for response to SGLT2 inhibitor therapy in this increasingly high-risk population. Full article