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10 pages, 710 KiB  
Article
CPAP Use and Retinal Disease Risk in Obstructive Apnea: A Cohort Study
by Dillan Cunha Amaral, Pedro Lucas Machado Magalhães, Muhammad Alfatih, Bruna Gabriel Miranda, Hashem Abu Serhan, Raíza Jacometti, Bruno Fortaleza de Aquino Ferreira, Letícia Sant’Ana, Diogo Haddad Santos, Mário Luiz Ribeiro Monteiro and Ricardo Noguera Louzada
Vision 2025, 9(3), 65; https://doi.org/10.3390/vision9030065 (registering DOI) - 1 Aug 2025
Abstract
Obstructive sleep apnea (OSA) is a common condition associated with intermittent hypoxia, systemic inflammation, and vascular dysfunction; mechanisms implicated in retinal disease pathogenesis. This real-world retrospective cohort study used data from the TriNetX Research Network to assess whether continuous positive airway pressure (CPAP) [...] Read more.
Obstructive sleep apnea (OSA) is a common condition associated with intermittent hypoxia, systemic inflammation, and vascular dysfunction; mechanisms implicated in retinal disease pathogenesis. This real-world retrospective cohort study used data from the TriNetX Research Network to assess whether continuous positive airway pressure (CPAP) therapy reduces retinal disease incidence among adults with OSA and BMI between 25.0 and 30.0 kg/m2. After 1:1 propensity score matching, 101,754 patients were included in the analysis. Retinal outcomes included diabetic retinopathy (DR), age-related macular degeneration (AMD), retinal vein occlusion (RVO), and central serous chorioretinopathy (CSC). CPAP use was associated with a modest but statistically significant reduction in DR (3.2% vs. 3.4%, RR: 0.922, p = 0.016) and AMD (2.1% vs. 2.3%, RR: 0.906, p = 0.018), while no significant differences were found for RVO or CSC. These findings support prior evidence linking CPAP to improved retinal microvascular health and suggest a protective effect against specific retinal complications. Limitations include a lack of data on CPAP adherence, OSA severity, and imaging confirmation. Still, this study highlights the importance of interdisciplinary care between sleep and eye health, and the need for further prospective studies to validate CPAP’s role in preventing retinal disease progression in OSA patients. Full article
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26 pages, 2343 KiB  
Review
Molecular Mechanisms of Microvascular Obstruction and Dysfunction in Percutaneous Coronary Interventions: From Pathophysiology to Therapeutics—A Comprehensive Review
by Andre M. Nicolau, Pedro G. Silva, Hernan Patricio G. Mejía, Juan F. Granada, Grzegorz L. Kaluza, Daniel Burkhoff, Thiago Abizaid, Brunna Pileggi, Antônio F. D. Freire, Roger R. Godinho, Carlos M. Campos, Fabio S. de Brito, Alexandre Abizaid and Pedro H. C. Melo
Int. J. Mol. Sci. 2025, 26(14), 6835; https://doi.org/10.3390/ijms26146835 - 16 Jul 2025
Viewed by 435
Abstract
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 [...] Read more.
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
(This article belongs to the Special Issue Cardiovascular Diseases: From Pathology to Therapeutics)
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25 pages, 1860 KiB  
Review
Advances in Pathophysiology and Novel Therapeutic Strategies for Coronary No-Reflow Phenomenon
by Hubert Borzuta, Wiktor Kociemba, Oliwia Bochenek, Monika Jarowicz and Agnieszka Wsół
Biomedicines 2025, 13(7), 1716; https://doi.org/10.3390/biomedicines13071716 - 14 Jul 2025
Viewed by 323
Abstract
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 [...] Read more.
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
(This article belongs to the Section Molecular and Translational Medicine)
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33 pages, 2002 KiB  
Review
Network Pharmacology Approaches to Myocardial Infarction Reperfusion Injury: Exploring Mechanisms, Pathophysiology, and Novel Therapies
by Joy Das, Ashok Kumar Sah, Ranjay Kumar Choudhary, Rabab H. Elshaikh, Utpal Bhui, Shreya Chowdhury, Anass M. Abbas, Manar G. Shalabi, Nadeem Ahmad Siddique, Raji Rubayyi Alshammari, Navjyot Trivedi, Khoula Salim Ali Buwaiqi, Said Al Ghenaimi and Pranav Kumar Prabhakar
Biomedicines 2025, 13(7), 1532; https://doi.org/10.3390/biomedicines13071532 - 23 Jun 2025
Viewed by 1587
Abstract
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 [...] Read more.
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
(This article belongs to the Section Molecular and Translational Medicine)
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35 pages, 8317 KiB  
Article
ResST-SEUNet++: Deep Model for Accurate Segmentation of Left Ventricle and Myocardium in Magnetic Resonance Imaging (MRI) Images
by Abduljabbar S. Ba Mahel, Mehdhar S. A. M. Al-Gaashani, Fahad Mushabbab G. Alotaibi and Reem Ibrahim Alkanhel
Bioengineering 2025, 12(6), 665; https://doi.org/10.3390/bioengineering12060665 - 17 Jun 2025
Viewed by 523
Abstract
The highly precise and trustworthy segmentation of the left ventricle (LV) and myocardium is critical for diagnosing and treating cardiovascular disorders, which includes persistent microvascular obstruction (MVO) as well as myocardial infarction (MI) diseases. This process improves diagnostic accuracy and optimizes the planning [...] Read more.
The highly precise and trustworthy segmentation of the left ventricle (LV) and myocardium is critical for diagnosing and treating cardiovascular disorders, which includes persistent microvascular obstruction (MVO) as well as myocardial infarction (MI) diseases. This process improves diagnostic accuracy and optimizes the planning and implementation of therapeutic interventions, ultimately improving the quality of care and patient prognosis. Limitations of earlier investigations include neglecting the complex image pre-processing required to accurately delineate areas of the LV and myocardium (Myo) in MRI and the absence of a substantial, high-quality dataset. Thus, this paper presents a comprehensive end-to-end framework, which includes contrast-limited adaptive histogram equalization (CLAHE) and bilateral filtering methods for image pre-processing and the development and implementation of a proposed deep model for left ventricular and myocardium segmentation. This study utilizes the EMIDEC database for the training and assessment of the model, allowing for a detailed comparative analysis with six state-of-the-art (SOTA) segmentation models. This approach provides a high accuracy and reliability for the segmentation that is crucial for the diagnosis and treatment of cardiovascular disorders. The achievements of the proposed model are demonstrated by high average values of segmentation rates, such as an Intersection over Union (IoU) of 93.73%, Recall of 96.54%, Dice coefficient of 96.70%, Precision of 96.86%, and F1-score of 96.70%. To verify the generalization capability, we assessed our suggested model on five supplementary databases, which substantiates its exceptional efficiency and adaptability in a diverse environment. The presented findings demonstrate that the proposed deep model surpasses current methods, offering more a precise and resilient segmentation of cardiac structures. Full article
(This article belongs to the Special Issue Medical Artificial Intelligence and Data Analysis)
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23 pages, 1590 KiB  
Review
Coronary Microvascular Disease Early After Myocardial Infarction: Diagnostic Approach and Prognostic Value—A Narrative Review
by Stefanos Sokratous, Andreas Mitsis, Elina Khattab, Dimitrios Karelas, Nikolaos Velidakis and Nikolaos P. E. Kadoglou
Biomedicines 2025, 13(6), 1289; https://doi.org/10.3390/biomedicines13061289 - 23 May 2025
Viewed by 825
Abstract
Coronary microvascular disease (CMVD) is not an uncommon complication after acute myocardial infarction (AMI), independent of prompt revascularization. It is a serious yet underdiagnosed disease that has a major impact on patient outcomes. Even when the infarct-related artery is successfully revascularized, a significant [...] Read more.
Coronary microvascular disease (CMVD) is not an uncommon complication after acute myocardial infarction (AMI), independent of prompt revascularization. It is a serious yet underdiagnosed disease that has a major impact on patient outcomes. Even when the infarct-related artery is successfully revascularized, a significant percentage of patients still have compromised microvascular circulation, which is linked to higher cardiovascular mortality and hospitalization for heart failure. The well-known invasive methods, such as the index of microvascular resistance (IMR) and the coronary flow reserve (CFR), have been considered as gold standards. However, they are constrained by their hazards and complexity. Non-invasive techniques, such as echocardiography Doppler for CFR assessment, positron emission tomography (PET), cardiac magnetic resonance imaging (CMR), and some other techniques provide alternatives, but their accessibility, cost and implementation during the peri-AMI period raise obstacles to their wider use. This review highlights both invasive and non-invasive modalities as it examines the diagnostic methods and prognostic significance of CMVD development early after AMI. Enhancing long-term results in this high-risk population requires a thorough understanding of pathophysiology and a commitment to larger diagnostic and prognostic studies for CMVD. Full article
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11 pages, 939 KiB  
Article
Intraventricular Thrombosis After Myocardial Infarction: Prognostic Evaluation in Relation to Microvascular Obstruction Extent by CMR
by Antonella Cecchetto, Francesco Zupa, Manuel De Lazzari, Angiola Bolis, Anna Baritussio, Stefano Nistri, Giorgio De Conti and Martina Perazzolo Marra
J. Clin. Med. 2025, 14(8), 2658; https://doi.org/10.3390/jcm14082658 - 13 Apr 2025
Viewed by 369
Abstract
(1) Background: There are few data on anticoagulation therapy for left ventricular (LV) thrombosis following ST-segment elevation myocardial infarction (STEMI). The aim of this study was to assess whether microvascular obstruction (MVO) extent on cardiac magnetic resonance (CMR) worsened the prognosis of [...] Read more.
(1) Background: There are few data on anticoagulation therapy for left ventricular (LV) thrombosis following ST-segment elevation myocardial infarction (STEMI). The aim of this study was to assess whether microvascular obstruction (MVO) extent on cardiac magnetic resonance (CMR) worsened the prognosis of patients with LV thrombosis receiving anticoagulation. (2) Methods: reperfused STEMI patients undergoing CMR were enrolled. Patients were divided into 4 groups according to MVO and LV thrombosis presence or absence. Occurrence of major adverse cardiac events (MACE) was evaluated during follow-up. (3) Results: 80 STEMI patients were enrolled. According to MVO and LV thrombosis, 4 subgroups were obtained: patients with MVO and LV thrombosis (21 patients, 26%); patients with MVO without LV thrombosis (28 patients, 35%); patients without MVO with LV thrombosis (6 patients, 8%); patients without MVO and LV thrombosis (25 patients, 31%). All patients with LV thrombosis were treated with anticoagulation therapy. The median time to the follow-up was 11 months. Twenty-two patients (27%) experienced MACE. LV thrombosis treated with anticoagulation was an independent predictor of MACE (hazard ratio, 2.828; 95% confidence interval, 1.205–6.638; p = 0.017) and was associated with a worse prognosis (p = 0.012), regardless of MVO (p = 0.852), at Kaplan–Meier. (4) Conclusions: Patients with LV thrombosis treated with anticoagulation after a reperfused STEMI have a worse prognosis than those without; however, MVO extent did not worsen prognosis. Full article
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18 pages, 945 KiB  
Review
Myocardial Infarction with Nonobstructive Coronary Arteries (MINOCA): Current Insights into Pathophysiology, Diagnosis, and Management
by Chiara Tognola, Alessandro Maloberti, Marisa Varrenti, Patrizio Mazzone, Cristina Giannattasio and Fabrizio Guarracini
Diagnostics 2025, 15(7), 942; https://doi.org/10.3390/diagnostics15070942 - 7 Apr 2025
Cited by 2 | Viewed by 4267
Abstract
Myocardial infarction with nonobstructive coronary arteries (MINOCA) is an increasingly recognized clinical entity characterized by myocardial injury in the absence of a significant coronary artery obstruction. MINOCA encompasses a diverse range of pathophysiological mechanisms, including coronary plaque disruption, coronary vasospasm, coronary microvascular dysfunction, [...] Read more.
Myocardial infarction with nonobstructive coronary arteries (MINOCA) is an increasingly recognized clinical entity characterized by myocardial injury in the absence of a significant coronary artery obstruction. MINOCA encompasses a diverse range of pathophysiological mechanisms, including coronary plaque disruption, coronary vasospasm, coronary microvascular dysfunction, thromboembolism, and spontaneous coronary artery dissection. A systematic diagnostic approach is essential to identify the underlying etiology and guide appropriate management strategies. Advanced imaging techniques, particularly cardiac magnetic resonance, play a pivotal role in distinguishing ischemic from non-ischemic myocardial injury and refining prognosis. Despite growing awareness, standardized treatment protocols remain limited, with current management largely extrapolated from strategies used in obstructive coronary artery disease. Notably, MINOCA is significantly more prevalent in women, emphasizing the need to understand sex-related differences in its pathophysiology, presentation, and clinical outcomes. This narrative review offers a comprehensive and up-to-date overview of MINOCA, including a dedicated chapter on sex-related considerations. It integrates recent advancements and highlights the importance of personalized management strategies. Full article
(This article belongs to the Special Issue Advances in the Diagnosis and Management of Cardiovascular Diseases)
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18 pages, 13833 KiB  
Article
Host Serine Proteases and Antiviral Innate Immunity as Potential Therapeutic Targets in Influenza A Virus Infection-Induced COPD Exacerbations
by Haiqing Bai, Melissa Rodas, Longlong Si, Yuncheng Man, Jie Ji, Roberto Plebani, Johnathan D. Mercer, Rani K. Powers, Chaitra Belgur, Amanda Jiang, Sean R. R. Hall, Rachelle Prantil-Baun and Donald E. Ingber
Int. J. Mol. Sci. 2025, 26(6), 2549; https://doi.org/10.3390/ijms26062549 - 12 Mar 2025
Viewed by 1246
Abstract
Lung manifestations of chronic obstructive pulmonary disease (COPD) are often exacerbated by influenza A virus infections; however, the underlying mechanisms remain largely unknown, and hence therapeutic options are limited. Using a physiologically relevant human lung airway-on-a-chip (Airway Chip) microfluidic culture model lined with [...] Read more.
Lung manifestations of chronic obstructive pulmonary disease (COPD) are often exacerbated by influenza A virus infections; however, the underlying mechanisms remain largely unknown, and hence therapeutic options are limited. Using a physiologically relevant human lung airway-on-a-chip (Airway Chip) microfluidic culture model lined with human airway epithelium from COPD or healthy donors interfaced with pulmonary microvascular endothelium, we observed that Airway Chips lined with COPD epithelium exhibit an increased sensitivity to influenza virus infection, as is observed clinically in COPD patients. Differentiated COPD airway epithelial cells display increased inflammatory cytokine production, barrier function loss, and mucus accumulation upon virus infection. Transcriptomic analysis revealed gene expression profiles characterized by upregulation of serine proteases that may facilitate viral entry and downregulation of interferon-related genes associated with antiviral immune responses. Importantly, treatment of influenza virus-infected COPD epithelium with a protease inhibitor, nafamostat, ameliorated the disease phenotype, as evidenced by dampened viral replication, reduced mucus accumulation, and improved tissue barrier integrity. These findings suggest that targeting host serine proteases may represent a promising therapeutic avenue against influenza-afflicted COPD exacerbations. Full article
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14 pages, 2696 KiB  
Article
Single-Center Analysis of Soluble TREM2 as a Biomarker in Coronary Microvascular Dysfunction: A Cross-Sectional Study
by Yingying Xie, Zhaoxue Sheng, Haoming He, Yike Li, Qiang Chen, Yanxiang Gao and Jingang Zheng
J. Clin. Med. 2025, 14(6), 1816; https://doi.org/10.3390/jcm14061816 - 7 Mar 2025
Viewed by 893
Abstract
Background: The soluble triggering receptor expressed on myeloid cells 2 (sTREM2) is linked to the progression of cardiovascular conditions, but its role in coronary microcirculation dysfunction (CMD) is not yet clear. Methods: A cross-sectional observational study from July 2023 to May 2024 was [...] Read more.
Background: The soluble triggering receptor expressed on myeloid cells 2 (sTREM2) is linked to the progression of cardiovascular conditions, but its role in coronary microcirculation dysfunction (CMD) is not yet clear. Methods: A cross-sectional observational study from July 2023 to May 2024 was conducted in the China–Japan Friendship Hospital, after registration in the ClinicalTrials database (Registry Name: Coronary Microvascular Dysfunction in Angina Patients With Non-obstructive Coronary Artery Disease (ANOCA-CMD); Registry Number: NCT06503640; Registry Date: 23 September 2022). This cross-sectional study involved 76 subjects, including 55 patients with CMD and 21 without CMD, admitted to the China–Japan Friendship Hospital. CMD was defined by a coronary flow reserve (CFR) < 2.5 or index of microvascular resistance (IMR) ≥ 25. sTREM2 levels were measured using an enzyme-linked immunosorbent assay. Linear correlation analysis assessed the relationship between sTREM2 levels and CFR, IMR, microvascular resistance reserve (MRR), and the resistive reserve ratio (RRR). Univariate and multivariate regression analyses further examined the association between sTREM2 and CMD. Additionally, receiver operating characteristic (ROC) analysis was used to evaluate the diagnostic accuracy of plasma sTREM2 for identifying CMD patients. Results: Elevated sTREM2 levels were found in the CMD group. Correlation analysis showed a significant positive relationship with IMR and an inverse correlation with CFR, MRR, and RRR. After adjusting for confounders, sTREM2 was found to be an independent risk factor for CMD [OR = 1.003, 95% CI 1.001–1.007, p = 0.008]. ROC analysis revealed a sensitivity of 59.46%, specificity of 90.48%, and an AUC of 0.7677 (95% CI: 0.6481–0.8872, p = 0.008) for CMD diagnosis at a threshold of 595.5 pg/mL, indicating good diagnostic performance. Conclusions: Elevated sTREM2 levels in CMD patients indicate its potential as a biomarker. Full article
(This article belongs to the Section Cardiovascular Medicine)
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11 pages, 793 KiB  
Article
Relationship Between Noninvasive Doppler-Derived Coronary Flow Reserve Measured by Transthoracic Echocardiography and Angiography Thermodilution-Measured Coronary Flow Reserve and the Index of Microcirculatory Resistance in Patients with Non-Obstructive Coronary Arteries
by Milenko Čanković, Aleksandra Milovančev, Snežana Tadić, Maja Stefanović, Milovan Petrović, Mila Kovačević, Igor Tomas, Dragana Dabović, Vladimir Ivanović, Aleksandra Ilić, Anastazija Stojšić-Milosavljević, Snežana Stojšić, Nikola Komazec, Bojan Mihajlović and Igor Ivanov
Biomedicines 2025, 13(2), 466; https://doi.org/10.3390/biomedicines13020466 - 14 Feb 2025
Viewed by 725
Abstract
Background/Objectives: Coronary microvascular dysfunction (CMD) is emerging as a critical factor in patients presenting with anginal symptoms without obstructive coronary artery disease (CAD). This study aims to investigate the relationship between invasive measurements of coronary flow reserve (CFR) and the index of [...] Read more.
Background/Objectives: Coronary microvascular dysfunction (CMD) is emerging as a critical factor in patients presenting with anginal symptoms without obstructive coronary artery disease (CAD). This study aims to investigate the relationship between invasive measurements of coronary flow reserve (CFR) and the index of microcirculatory resistance (IMR) using thermodilution techniques, compared to non-invasive assessments of CFR with transthoracic Doppler echocardiography (TDE). Methods: In this observational prospective cross-sectional study, a total of 49 patients, clinically characterized as having angina with no obstructive CAD (ANOCA) or ischemia with no obstructive CAD (INOCA), underwent both TDE and invasive coronary angiography (ICA) followed by thermodilution assessment of CFR and IMR. Results: It was found that there is a statistically significant negative correlation between both non-invasive and invasive CFR measurements and IMR. Specifically, a negative moderate correlation was observed between non-invasive CFR and IMR (rs = −0.477, p < 0.01), as well as a high negative correlation between invasive CFR and IMR (r = −0.541, p < 0.01). Receiver operating characteristic (ROC) analysis indicated that both non-invasive and invasive CFRs are effective predictors of CMD, defined as IMR > 25. Conclusions: Both noninvasive and invasive CFR measurements are significant independent predictors of CMD. Our results indicate that noninvasive TDE CFR can be a reliable tool for assessing CMD in patients with ANOCA, potentially facilitating earlier diagnosis and management strategies for this patient population. Full article
(This article belongs to the Special Issue Microcirculation in Health and Diseases)
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9 pages, 480 KiB  
Review
Benefits of Treating Obstructive Sleep Apnea in Cognition: Systematic Literature Review
by Júlia Montalvão Neves, Cátia Andreia Maciel and Pedro Alexandre-Sousa
J. Dement. Alzheimer's Dis. 2025, 2(1), 3; https://doi.org/10.3390/jdad2010003 - 3 Feb 2025
Viewed by 3379
Abstract
Introduction: Obstructive sleep apnea syndrome (OSAS) is characterized by intermittent hypoxia, sleep fragmentation, daytime sleepiness, cognitive impairment, and brain cell damage due to brain blood flow reduction, with ischemic damage, increased microvascular reactivity, and brain tissue damage. OSAS is strongly linked to chronic, [...] Read more.
Introduction: Obstructive sleep apnea syndrome (OSAS) is characterized by intermittent hypoxia, sleep fragmentation, daytime sleepiness, cognitive impairment, and brain cell damage due to brain blood flow reduction, with ischemic damage, increased microvascular reactivity, and brain tissue damage. OSAS is strongly linked to chronic, neurodegenerative, and inflammatory cerebrovascular disease and cognitive impairment. Continuous positive airway pressure (CPAP) is the first-line treatment for OSAS. Objective: This article aims to evaluate the effect of CPAP treatment on neurocognitive performance in OSAS patients with mild cognitive impairment or dementia by reviewing the literature. Methods: We performed a comprehensive review of the Portuguese and English languages without a time limit using the following Mesh terms: dementia, mild cognitive impairment, obstructive sleep apnea, and CPAP. We included randomized controlled trials (RCTs), meta-analyses, and systematic reviews (SRs) where the impact of CPAP on neurocognitive performance was addressed. Results: Five SRs and three RCTs reported significant improvements in neurocognitive performance, especially in verbal, visuospatial, and working memory. Conclusion: CPAP treatment seems to improve cognitive defects associated with OSA. Full article
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15 pages, 873 KiB  
Systematic Review
Evolution of Coronary Microvascular Dysfunction Prevalence over Time and Across Diagnostic Modalities in Patients with ANOCA: A Systematic Review
by Aurelia Zimmerli, Adil Salihu, Panagiotis Antiochos, Henri Lu, Barbara Pitta Gros, Alexandre Berger, Olivier Muller, David Meier and Stephane Fournier
J. Clin. Med. 2025, 14(3), 829; https://doi.org/10.3390/jcm14030829 - 27 Jan 2025
Cited by 1 | Viewed by 1487
Abstract
Background: A considerable number of patients with angina undergo invasive coronary angiography, which might reveal non-obstructive coronary arteries (ANOCA). In this setting, they might have coronary microvascular disease (CMD). Its prevalence significantly varies in the literature. This systematic review aims to document the [...] Read more.
Background: A considerable number of patients with angina undergo invasive coronary angiography, which might reveal non-obstructive coronary arteries (ANOCA). In this setting, they might have coronary microvascular disease (CMD). Its prevalence significantly varies in the literature. This systematic review aims to document the prevalence of CMD over time according to the diagnostic modalities. Methods: A systematic literature review was conducted using PubMed, the Cochrane Library, and Embase, covering publications from inception to 1 May 2024. Among 1471 identified articles, 297 full-text articles were assessed for eligibility. All studies reporting the prevalence of CMD in ANOCA patients based on invasive coronary artery (ICA), positron emission tomography–computed tomography (PET-CT), transthoracic echocardiography (TTE), or cardiac magnetic resonance (CMR) were included. Results: The review included 53 studies (published between 1998 and 2024), encompassing a total of 16,602 patients. Of these studies, 23 used ICA, 15 used PET-CT, 8 used TTE, and 7 used CMR. A statistically significant increase in CMD prevalence over time was observed across all diagnostic modalities (p < 0.05), except for PET-CT, which showed a consistent and stable prevalence over time. Notably, the prevalence rates from all of the diagnostic methods converged towards the 50% prevalence detected by PET-CT. Conclusions: The prevalence of CMD in patients with ANOCA is subject to debate. However, the current data suggest that regardless of the diagnostic method used, the most recent studies tend to converge towards a prevalence value of 50%, which has been consistently reported by PET-CT from the beginning. Full article
(This article belongs to the Section Cardiovascular Medicine)
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25 pages, 15907 KiB  
Article
Antiedemic Effect of the Myosin Light Chain Kinase Inhibitor PIK7 in the Rat Model of Myocardial Ischemia Reperfusion Injury
by Dmitry L. Sonin, Mikhail S. Medved, Asker Y. Khapchaev, Maria V. Sidorova, Marina E. Palkeeva, Olga A. Kazakova, Garry V. Papayan, Daniil A. Mochalov, Sarkis M. Minasyan, Ilya E. Anufriev, Daria V. Mukhametdinova, Natalia M. Paramonova, Ksenia M. Balabanova, Anastasia S. Lopatina, Ilia V. Aleksandrov, Natalya Yu. Semenova, Anna A. Kordyukova, Kirill V. Zaichenko, Vladimir P. Shirinsky and Michael M. Galagudza
Curr. Issues Mol. Biol. 2025, 47(1), 33; https://doi.org/10.3390/cimb47010033 - 6 Jan 2025
Viewed by 1112
Abstract
Myocardial ischemia-reperfusion injury increases myocardial microvascular permeability, leading to enhanced microvascular filtration and interstitial fluid accumulation that is associated with greater microvascular obstruction and inadequate myocardial perfusion. A burst of reactive oxygen species and inflammatory mediators during reperfusion causes myosin light chain kinase [...] Read more.
Myocardial ischemia-reperfusion injury increases myocardial microvascular permeability, leading to enhanced microvascular filtration and interstitial fluid accumulation that is associated with greater microvascular obstruction and inadequate myocardial perfusion. A burst of reactive oxygen species and inflammatory mediators during reperfusion causes myosin light chain kinase (MLCK)-dependent endothelial hyperpermeability, which is considered a preventable cause of reperfusion injury. In the present study, a single intravenous injection of MLCK peptide inhibitor PIK7 (2.5 mg/kg or 40 mg/kg) was found to suppress the vascular hyperpermeability caused by ischemia/reperfusion injury in an in vivo rat model. The antiedemic effect of PIK7 is transient and ceases within 90 min of reperfusion. The early no-reflow detected for the first time after 30 min ischemia in this model of myocardial infarction reduces the area accessible for PIK7. Electron microscopy has shown membrane-bound blebs of endotheliocytes, which partially or completely obturate the capillary lumen, and few capillaries with signs of intercellular gap formation in samples obtained from the center of the early no-reflow zone in control and PIK7-injected rats. Co-injection of PIK7 with NO donor sodium nitroprusside (SNP) increases blood flow in the zone of early no-reflow, while reducing the increased vascular permeability caused by SNP. Full article
(This article belongs to the Section Molecular Medicine)
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15 pages, 1192 KiB  
Review
Specificities of Myocardial Infarction and Heart Failure in Women
by Milica Dekleva, Ana Djordjevic, Stefan Zivkovic and Jelena Suzic Lazic
J. Clin. Med. 2024, 13(23), 7319; https://doi.org/10.3390/jcm13237319 - 2 Dec 2024
Cited by 1 | Viewed by 1642
Abstract
Substantial evidence from previous clinical studies, randomized trials, and patient registries confirms the existence of significant differences in cardiac morphology, pathophysiology, prevalence of specific coronary artery disease (CAD), and clinical course of myocardial infarction (MI) between men and women. The aim of this [...] Read more.
Substantial evidence from previous clinical studies, randomized trials, and patient registries confirms the existence of significant differences in cardiac morphology, pathophysiology, prevalence of specific coronary artery disease (CAD), and clinical course of myocardial infarction (MI) between men and women. The aim of this review is to investigate the impact of sex or gender on the development and clinical course of MI, the mechanisms and features of left ventricular (LV) remodeling, and heart failure (HF). The main sex-related difference in post-MI LV remodeling is adverse LV dilatation in males versus concentric LV remodeling or concentric LV hypertrophy in females. In addition, women have a higher incidence of microvascular dysfunction, which manifests as impaired coronary flow reserve, distal embolism, and a higher prevalence of the no-reflow phenomenon. Consequently, impaired myocardial perfusion after MI is more common in women than in men. Regardless of age or other comorbidities, the incidence of reinfarction, hospitalization for HF, and mortality is significantly higher in females. There is therefore a “sex paradox”: despite the lower prevalence of obstructive CAD and HF with reduced ejection fraction (HFrEF), women have a higher mortality rate after MI. Different characteristics of the coronary network, such as plaque formation, microvascular dysfunction, and endothelial inflammation, as well as the prolonged time to optimal coronary flow restoration, secondary mitral regurgitation, and pulmonary vascular dysfunction, lead to a worse outcome in females. A better understanding of the mechanisms responsible for MI occurrence, LV remodeling, and HF in men and women would contribute to optimized patient therapy that would benefit both sexes. Full article
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