Search Results (261)

Coronary artery disease (CAD) constitutes a major contributor to morbidity, mortality and healthcare burden worldwide. Recent innovations in imaging modalities, pharmaceuticals and interventional techniques have revolutionized diagnostic and treatment options, necessitating the reevaluation of established drug protocols or the consideration of newer alternatives. The utilization of beta blockers (BBs) in the setting of acute myocardial infarction (AMI), shifting from the pre-reperfusion to the thrombolytic and finally the primary percutaneous coronary intervention (pPCI) era, has become increasingly more selective and contentious. Nonetheless, the extent of myocardial necrosis remains a key predictor of outcomes in this patient population, with large trials establishing the beneficial use of beta blockers. Computed tomography coronary angiography (CTCA) has emerged as a highly effective diagnostic tool for delineating the coronary anatomy and atheromatous plaque characteristics, with the added capability of MESH-3D model generation. Induction and preservation of a low heart rate (HR), regardless of the underlying sequence, is of critical importance for high-quality results. Landiolol is an intravenous beta blocker with an ultra-short duration of action (t1/2 = 4 min) and remarkable β1-receptor specificity (β1/β2 = 255) and pharmacokinetics that support its potential for systematic integration into clinical practice. It has been increasingly recognized for its importance in both acute (primarily studied in STEMI and, to a lesser extent, NSTEMI pPCI) and chronic (mainly studied in elective PCI) CAD settings. Given the limited literature focusing specifically on landiolol, the aim of this narrative review is to examine its pharmacological properties and evaluate its current and future role in enhancing both diagnostic imaging quality and therapeutic outcomes in patients with CAD. Full article

Coronary microvascular obstruction and dysfunction (CMVO) frequently arise following primary percutaneous coronary intervention (PCI), particularly in individuals with myocardial infarction. Despite the restoration of epicardial blood flow, microvascular perfusion might still be compromised, resulting in negative clinical outcomes. CMVO is a complex condition resulting from a combination of ischemia, distal thrombotic embolization, reperfusion injury, and individual susceptibilities such as inflammation and endothelial dysfunction. The pathophysiological features of this condition include microvascular spasm, endothelial swelling, capillary plugging by leukocytes and platelets, and oxidative stress. Traditional angiographic assessments, such as Thrombolysis in Myocardial Infarction (TIMI) flow grade and myocardial blush grade, have limited sensitivity. Cardiac magnetic resonance imaging (CMR) stands as the gold standard for identifying CMVO, while the index of microvascular resistance (IMR) is a promising invasive option. Treatment approaches involve powerful antiplatelet drugs, anticoagulants, and supersaturated oxygen, yet no treatment has been definitively shown to reverse established CMVO. CMVO remains a significant therapeutic challenge in coronary artery disease management. Enhancing the comprehension of its core mechanisms is vital for the development of more effective and personalized treatment strategies. Full article

Coronary no-reflow (CNR) is the failure of blood to reperfuse ischemic myocardial tissue after restoration of the vasculature. CNR poses a significant clinical challenge in the treatment of patients with ST-segment elevation myocardial infarction (STEMI), as it increases mortality and the risk of major adverse cardiac events (MACEs). Myocardial ischemia with subsequent reperfusion results in severe damage to the cardiac microcirculation. The pathophysiological causes of CNR include cardiomyocyte vulnerability, capillary and endothelial damage, leukocyte activation, reactive oxygen species (ROS) production, and changes in microRNA profiles and related gene expression. The impact of percutaneous coronary intervention (PCI) on the occurrence of CNR cannot be overlooked, as it can provoke distal atherothrombotic embolization. Current standards of pharmacological therapy for CNR are confined to intracoronary vasodilators and antiplatelet agents. As our understanding of the pathogenesis of the CNR phenomenon improves, opportunities emerge for developing novel therapeutic strategies. The following literature review provides an overview of the pathophysiology of the no-reflow phenomenon (based on animal and preclinical studies), contemporary treatment trends, and current therapeutic approaches. Full article

Introduction: Postoperative atrial fibrillation (POAF) is a common complication after heart surgery, adversely impacting clinical outcomes and healthcare costs. Little is known about the dynamics of nucleotide metabolism associated with the development of POAF at a ventricular level. We conducted a post hoc trial analysis to investigate the changes in ventricular adenine nucleotides and the clinical predictors associated with the development of AF. Methods: Using data from a randomised trial, we analysed ATP/ADP, ATP/AMP, and energy charges in left and right ventricular biopsies of patients who developed AF compared to non-AF patients. A logistic regression model was used to understand the predictors associated with the development of atrial fibrillation in this cohort. Results: We analysed adenine nucleotide levels available in 88 patients who underwent coronary artery bypass grafting (CABG) (n = 65) and aortic valve replacement (AVR) (n = 23), out of which 27 (31%) developed a new onset of AF. Seventeen (43.4%) patients in the CABG group and ten (26.15%) in the AVR group developed AF. The patients who developed postoperative AF had longer cross-clamp times for CABG (p = 0.013) and AVR (p = 0.002). The most significant predictors for AF development were age (p = 0.003) and cross-clamp time (p = 0.012). In patients undergoing CABG who developed AF, we found a significant drop in post-reperfusion ATP/ADP and ATP/AMP ratios compared to pre-reperfusion. This was not significant for the patients who underwent AVR. Furthermore, the patients who underwent CABG and developed AF had higher pre- and post-reperfusion ATP/ADP ratios and energy charges than non-AF patients, suggesting a higher reserve of cardiac nucleotides. Conclusions: The development of postoperative atrial fibrillation is associated with intraoperative changes in the ventricular adenine nucleotide metabolism of patients undergoing CABG. In the clinical analysis, age and cross-clamp time were significant predictors of AF development. Full article

Poloxamer (P) 188 attenuates myocardial ischemia/reperfusion injury through cell membrane stabilization. Cell–cell interactions between endothelial cells (ECs) and cardiomyocytes (CMs) further protect CMs: co-cultures showed that, at an optimal density, ECs protected CMs against hypoxia/reoxygenation (HR) injury. The mechanism of interaction with P188 still requires exploration. We examined if N(ω)-nitro-L-arginine methyl ester (LNAME), a non-specific nitric oxide (NO) synthase inhibitor, abolishes protection in the presence or absence of P188 and/or ECs. We co-cultured mouse coronary artery ECs in an insert atop mouse CMs plated at confluency on the bottom of a well. Normoxic controls remained in complete media while HR groups were exposed to 24 h hypoxia at 0.01% O₂ in serum- and glucose-free media, followed by 2 h reoxygenation in complete media. P188 (300 μM), LNAME (40 mM), or vehicle were administered upon reoxygenation. ECs at the used lower density did not decrease HR-triggered lactate dehydrogenase release or calcium overload in CMs by themselves. P188 reduced both indicators after HR by 16/18% without and by 22/25% with ECs, respectively. LNAME abrogated CM protection by P188. Neither intervention had an effect under normoxia. Our co-culture data indicates that P188 requires NO, not necessarily of endothelial origin, to elicit CM protection. Full article

Myocardial infarction (MI) remains a leading cause of morbidity and mortality worldwide. While timely reperfusion therapies such as percutaneous coronary intervention (PCI) and thrombolysis are essential for salvaging ischemic myocardium, they can paradoxically exacerbate tissue injury through a process known as myocardial infarction reperfusion injury (MIRI). MIRI can contribute to up to 50% of the final infarct size, significantly diminishing the benefits of revascularization and leading to worsened cardiac outcomes. The pathophysiology of MIRI involves complex, interrelated mechanisms including oxidative stress, calcium overload, mitochondrial dysfunction, inflammatory responses, apoptosis, and dysregulated autophagy. Post-reperfusion recovery is further complicated by structural and functional abnormalities such as microvascular obstruction, endothelial dysfunction, and myocardial stunning. Clinically, distinguishing reperfusion injury from ischemic damage is challenging and often requires the use of sensitive biomarkers, such as cardiac troponins, alongside advanced imaging modalities. Although a range of pharmacological (e.g., antioxidants, calcium channel blockers, mitochondrial stabilizers, anti-inflammatory agents) and non-pharmacological (e.g., hypothermia, gene therapy, stem cell-based therapies) interventions have shown promise in preclinical studies, their clinical translation remains limited. This is largely due to the multifactorial and dynamic nature of MIRI. In this context, network pharmacology offers a systems-level approach to understanding the complex biological interactions involved in MIRI, facilitating the identification of multi-target therapeutic strategies. Integrating network pharmacology with omics technologies and precision medicine holds potential for advancing cardioprotective therapies. This review provides a comprehensive analysis of the molecular mechanisms underlying MIRI, examines the current clinical challenges, and explores emerging therapeutic strategies. Emphasis is placed on bridging the translational gap through validated, multi-target approaches and large-scale, multicenter clinical trials. Ultimately, this work aims to support the development of innovative and effective interventions for improving outcomes in patients with myocardial infarction. Full article

Background: Antegrade root cardioplegia remains the most popular strategy for myocardial protection during coronary artery bypass graft (CABG) performed with cardiopulmonary bypass (CPB) and aortic cross clamp. In patients with depressed left ventricular function, however, especially if associated with severe multiple coronary stenosis, increased pharmacological and/or mechanical support in the early post-CPB period is often required to support left ventricular recovery. In this study, we analyzed the results of a myocardial protection strategy that includes selective infusion of cardioplegia through each venous graft followed by warm reperfusion distal to each coronary anastomosis until complete removal of the aortic clamp (total antegrade cardioplegia infusion and warm reperfusion = TAWR) to improve early postoperative recovery in patients with depressed left ventricular function undergoing multi-vessel CABG. Methods: Out of 97 patients undergoing CABG using the TAWR strategy for myocardial protection, 32 patients presented with depressed left ventricle function (EF < 40%) and multi-vessel coronary diseases requiring ≥2 vein grafts and were enrolled as Group A. Combined primary outcomes and postoperative early and late left ventricle recovery (including spontaneous rhythm recovery, inotropic support and postoperative troponin release) were analyzed and compared with those of 32 matched patients operated on using standard antegrade root cardioplegia and limited warm reperfusion through LIMA graft (SAWR) enrolled as Group B. Results: Two patient died in hospital (in-hospital mortality 3.1%) with no statistical differences between the two groups. In Group A 27 patients (90%) had spontaneous recovery of idiopathic rhythm compared to 17 (53%) in group B (p = 0.001). Early inotropic support was required in nine patients (28%) of group A and seventeen patients (53%) of group B (p = 0.041). Furthermore, in eight patients (25%) of group A and seventeen (53%) of group B (p = 0.039) inotropic support was continued for >48 h. Conclusions: The TAWR strategy seems to significantly improve early postoperative cardiac recovery in patients with left ventricle depression undergoing multi-vessel CABG, when compared with SAWR strategy and could therefore be considered the strategy of choice in this subset of patients. Full article

Objectives: Contrast-induced acute kidney injury (CI-AKI) remains a frequent and serious complication after cardiac catheterization. Sirtuin-1 (SIRT1), a NAD+-dependent deacetylase, plays a central role in renal protection against ischemia-reperfusion injury, inflammation, and vascular dysfunction. We aimed to investigate whether serum SIRT1 levels could serve as an early diagnostic biomarker for CI-AKI. Methods: This prospective case-control study included 50 patients undergoing elective percutaneous coronary intervention (PCI) for stable angina. Serum SIRT1 levels were measured at baseline, 24 h, and 72 h post-PCI. The occurrence of CI-AKI was defined by a standard rise in serum creatinine, and patients were stratified accordingly. Results: Although SIRT1 levels tended to be lower in patients who developed CI-AKI (n = 17) compared to those without (n = 33), the differences were not statistically significant at any time point (p > 0.05). However, a significant between-group difference was observed in the 72-h change in SIRT1 levels (Δ0–72 h, p = 0.037), with a greater decline in the CI-AKI group. Multivariable logistic regression also revealed a trend-level inverse association between 72-h SIRT1 levels and CI-AKI (β = −0.536, p = 0.099). Conclusions: While SIRT1 is biologically plausible as a renal protective factor, our findings suggest that serial SIRT1 measurement may offer added value as a dynamic biomarker rather than a static diagnostic tool. Confirmatory trials incorporating serial SIRT1 measurements may help translate this molecular signal into clinically actionable tools for early detection of CI-AKI. Full article

Background: Cardiogenic shock (CS) is a life-threatening complication of ST-elevation myocardial infarction (STEMI) and remains the leading cause of in-hospital mortality, with rates ranging from 5 to 10% despite advances in reperfusion strategies. Early identification and timely intervention are critical for improving outcomes. This study investigates the utility of machine learning (ML) models for predicting the risk of CS during the early phases of care—prehospital, emergency department (ED), and cardiology-on-call—with a focus on accurate triage and prioritization for urgent angiography. Results: In the prehospital phase, the Extra Trees classifier demonstrated the highest overall performance. It achieved an accuracy (ACC) of 0.9062, precision of 0.9078, recall of 0.9062, F1-score of 0.9061, and Matthews correlation coefficient (MCC) of 0.8140, indicating both high predictive power and strong generalization. In the ED phase, the support vector machine model outperformed others with an ACC of 78.12%. During the cardiology-on-call phase, Random Forest showed the best performance with an ACC of 81.25% and consistent values across other metrics. Quadratic discriminant analysis showed consistent and generalizable performance across all early care stages. Key predictive features included the Killip class, ECG rhythm, creatinine, potassium, and markers of renal dysfunction—parameters readily available in routine emergency settings. The greatest clinical utility was observed in prehospital and ED phases, where ML models could support the early identification of critically ill patients and could prioritize coronary catheterization, especially important for centers with limited capacity for angiography. Conclusions: Machine learning-based predictive models offer a valuable tool for early risk stratification in STEMI patients at risk for cardiogenic shock. These findings support the implementation of ML-driven tools in early STEMI care pathways, potentially improving survival through faster and more accurate decision-making, especially in time-sensitive clinical environments. Full article

Background: While early risk stratification in STEMI is essential, the threat of cardiogenic shock (CS) persists after revascularization due to reperfusion injury and evolving instability. However, risk prediction in later phases—after revascularization—is less explored, despite its importance in guiding intensive care decisions. This study evaluates machine learning (ML) models for dynamic risk assessment in interventional cardiology and cardiac intensive care unit (CICU) phases, where timely detection of deterioration can guide treatment escalation. Methods: We retrospectively analyzed clinical and procedural data from 158 patients diagnosed with STEMI complicated by cardiogenic shock, treated between 2019 and 2022 at the Cardiology Department of the University Emergency Hospital of Bucharest, Romania. Machine learning models—Random Forest (RF), and Quadratic Discriminant Analysis (QDA)—were developed and tested specifically for the interventional cardiology and CICU phases. Model performance was evaluated using area under the receiver operating characteristic curve (ROC-AUC), accuracy (ACC), sensitivity, specificity, and F1-score. Results: In the interventional phase, RF and QDA achieved the highest accuracy, both reaching 87.50%. In the CICU, RF and QDA demonstrate the best performance, reaching ACCs of 0.843. QDA maintained consistent performance across phases. Relevant predictors included reperfusion strategy, TIMI flow before percutaneous coronary intervention (PCI), Killip class, creatinine, and Creatine Kinase Index (CKI)—all parameters routinely assessed in STEMI patients. These models effectively identified patients at risk for post-reperfusion complications and hemodynamic decline, supporting decisions regarding extended monitoring and ICU-level care. Conclusions: Predictive models implemented in advanced STEMI phases can contribute to dynamic, phase-specific risk reassessment and optimize CICU resource allocation. These findings support the integration of ML-based tools into post-PCI workflows, enabling earlier detection of clinical decline and more efficient deployment of intensive care resources. When combined with earlier-stage models, the inclusion of interventional and CICU phases forms a dynamic, end-to-end risk assessment framework. With further refinement, this system could be implemented as a mobile application to support clinical decisions throughout the STEMI care continuum. Full article

Myocardial ischemia–reperfusion injury (MI/R) is a negative and adverse cardiovascular outcome following myocardial ischemia, cardiac surgery, or circulatory arrest. Prolyl endopeptidase (PREP) appears to be involved in inflammatory responses, so it could be a possible therapeutic target for counteracting ischemia injury. This study aimed to investigate the role of PREP inhibitor, KYP-2047 (4-phenylbutanoyl-l-prolyl-2(S)-cyanopyrolidine), in the modulation of molecular and biochemical processes involved in MI/R. MI/R was induced through coronary artery occlusion (15 min), followed by reperfusion (2 h). KYP-2047 was intraperitoneally administrated at doses of 2.5 mg/kg and 5 mg/kg 24 h before the surgical procedures. The hearts were removed and processed for analysis. KYP-2047 treatment limited ischemic myocardial-induced histological damage and neutrophil accumulation, limiting inflammation, fibrosis, and apoptosis processes. Additionally, KYP-2047 was able to modulate p-38 and p-ERK expression, suggesting an improving role in recovering cardiac function. These findings highlighted the protective effects of KYP-2047 pretreatment in MI/R injury, suggesting PREP as a potential target therapy for the pathogenesis of MI/R. Although the molecular mechanisms underlying the action of KYP-2047 are still to be explored, these results suggested that the regulation of NF-κB, apoptosis, and MAPK pathways by KYP-2047 treatment could preventatively limit the damage caused by MI/R. Full article

Background: ST-elevation myocardial infarction (STEMI) is a life-threatening emergency. Primary percutaneous coronary intervention (PPCI) is the preferred reperfusion strategy, provided it is performed promptly (within 120 min of the ECG-based diagnosis). However, the failure rate of PPCI remains high, particularly in patients with more severe conditions, potentially leading to serious complications. Objective: Through this case, we want to introduce coronary fibrinolysis as a rescue therapy after failing with primary PPCI. Methods: Case report. Results: We reported a clinical case of a STEMI patient who underwent coronary fibrinolysis as a rescue therapy after PPCI failure. The patient was a 62-year-old male patient who was a 40-pack-year smoker. He was diagnosed with STEMI and immediately received PPCI, but the aspiration process and angioplasty were unsuccessful. Subsequently, we decided to use coronary fibrinolysis and the follow-up coronary angiography showed coronary revascularization, and chest pain was resolved. Conclusions: This case highlighted a potential therapeutic approach of coronary fibrinolysis for patients experiencing PPCI failure. Full article

Acute coronary syndrome (ACS) and stroke are interconnected conditions that often share risk factors such as atherosclerosis, thrombosis, and systemic inflammation. When these events occur simultaneously, they present unique diagnostic and therapeutic challenges. This review explores the pathophysiological mechanisms linking ACS and stroke, including common pathways like plaque instability, cardioembolism, and endothelial dysfunction, while highlighting the distinct features of ischemic and hemorrhagic strokes. The manuscript provides an overview of diagnostic strategies, emphasizing the role of biomarkers, advanced neuroimaging, and risk stratification tools in guiding acute management. Furthermore, the review delves into treatment approach, emphasizing the need to balance reperfusion therapies for ACS with thrombolysis or thrombectomy for ischemic stroke while carefully managing the challenges posed by anticoagulation in cases complicated by bleeding. Long-term strategies for secondary prevention are examined, including antithrombotic regimens tailored to the dual risk of thrombosis and bleeding, as well as lipid-lowering and blood pressure management. Future perspectives highlight the potential of novel pharmacological agents, neuroprotective therapies, and AI-driven tools to enhance patient outcomes. This review underscores the importance of integrated, multidisciplinary care and identifies key areas for future research to optimize the management of these high-risk patients. Full article

Background and Objectives: The purpose of this study was to determine the factors that cause delay time in patients admitted to the hospital with STEMI. In addition, the effect of this delay on the patient’s prognosis has also been investigated. Materials and Methods: a total of 301 patients diagnosed with STEMI treated with primary percutaneous coronary intervention (pPCI) were included in the study. Reinfarction, revascularization, cerebrovascular event, and cardiac death were determined as major cardiac clinical events. The follow-up period of our study was 475 ± 193 days. Results: Univariate analysis revealed that factors influencing delay time included BMI, hypertension diabetes, smoking habit and variability in pain intensity. In multivariate logistic regression analysis, BMI, diabetes, hypertension, smoking, variation in pain intensity, and infarct-related artery other than the LAD were identified as independent factors associated with increased delay times. We determined the cut-off values predicting the composite endpoint as 122.5 min for patient delay, 95.5 min for system delay, and 371 min for total ischemic time. It was observed that the in-hospital NT pro-BNP values of the patients presenting early were lower (181 vs. 594 pg/mL p < 0.001), had a higher ejection fraction at the first measurement, and even improved at the sixth week of follow-up (p = 0.047). Conclusions: Prolonged ischemia duration was associated with several factors. Early reperfusion in STEMI patients reduces both cardiac death and clinical events. Delays are influenced by patient awareness, emergency care efficiency, and hospital-specific factors. Improving education, response times, and hospital protocols is essential to minimize delays and improve outcomes. Full article

Left ventricular thrombosis (LVT) is one of the most feared complications of both ischemic and non-ischemic cardiopathy, and despite its incidence having decreased over the years (mostly due to novel reperfusion therapies in acute coronary syndromes), it is still not negligible. If transthoracic echocardiography, possibly with the adjunction of echo contrast, represents the cornerstone in LVT diagnosis, sometimes it is found to be nonconclusive and advanced cardiovascular imaging, namely cardiac magnetic resonance, needs to be performed to fully exclude intraventricular masses or to better characterize them. Vitamin K antagonists always represented the anticoagulant of choice for the treatment of LVT; however, the recent spread of direct oral anticoagulants (DOACs) pushed clinicians to adopt them also in this setting despite the absence of robust evidence in their favor. If the optimal duration of anticoagulation for the treatment of LVT in non-ischemic cardiopathy is still a matter of debate, an initial treatment of 3–6 months seems to be reasonable in the setting of ischemic cardiopathy, with possible extension according to the follow-up findings. High-quality randomized studies are strongly needed to evaluate the potential role of prophylactic anticoagulation in high-risk patients and provide conclusive evidence for the use of DOACs in LVT treatment. Full article