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Search Results (965)

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13 pages, 733 KB  
Article
The Lazarus Phenomenon Among Older People—A Descriptive Analysis of Cases Spanning over 40 Years
by Małgorzata Grześkowiak, Anna Kluzik, Piotr Rzeźniczek and Agnieszka Danuta Gaczkowska
J. Clin. Med. 2026, 15(13), 4855; https://doi.org/10.3390/jcm15134855 (registering DOI) - 23 Jun 2026
Abstract
The Lazarus phenomenon (LP), also called auto-resuscitation, may happen after the end of ineffective cardiopulmonary resuscitation (CPR), or after death is confirmed in a person who did not undergo CPR, and heart activity returns spontaneously. The aim of the study was to focus [...] Read more.
The Lazarus phenomenon (LP), also called auto-resuscitation, may happen after the end of ineffective cardiopulmonary resuscitation (CPR), or after death is confirmed in a person who did not undergo CPR, and heart activity returns spontaneously. The aim of the study was to focus on older individuals (aged >60) experiencing the LP and to analyse distractors that cause this phenomenon. Methods. PubMed, Scopus, and Web of Science electronic databases were searched to find cases of LP from the year 1982 until 31 December 2025. Of the 81 total cases found, 48 patients were included in the study. For the analysis they were divided into two subgroups dependent on age: No 1 (60–79), No 2 (≥80). Results. Based on the descriptive analysis, the causes of cardiac arrest were divided almost equally between cardiac and non-cardiac causes (47.6% and 52.3% respectively). Cardiac arrest occurred equally in the IH and OH. In 16 out of 37 cases where such data were reported, a return to consciousness was confirmed, representing 43.2%. Conclusions. In older people, even those of very advanced age, the Lazarus phenomenon may occur. Based on the analysis carried out and given the lack of available data and the small sample size (48 individuals), it is not possible at this stage to definitively identify the causes of LP in the elderly population. As a potential cause of LP, age-related changes should be taken into account. Given that LP also occurs in the older population, consideration should be given to the need for extended monitoring of vital signs following the declaration of death. With a view to raising awareness of LP, it seems appropriate to include information on this phenomenon in the CPR guidelines. Full article
(This article belongs to the Section Anesthesiology)
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20 pages, 3508 KB  
Article
Effects of Empagliflozin Combined with Anaerobic, Aerobic, and Endurance Swimming Protocols on Cardiac Structure and Electrophysiology in Healthy Rats
by Samet Yavuz, Şahhan Kilic, Suha Asal, Mert Babaoglu, Cumaali Demirtaş, Mehmet Yildirim, Servet Altay and Ahmet Lütfullah Orhan
J. Clin. Med. 2026, 15(12), 4773; https://doi.org/10.3390/jcm15124773 (registering DOI) - 19 Jun 2026
Viewed by 181
Abstract
Objective: Sodium–glucose cotransporter 2 (SGLT2) inhibitors, particularly empagliflozin, have attracted considerable attention because of their cardiovascular benefits beyond glycemic control. However, the interaction between empagliflozin and exercise-induced physiological cardiac remodeling in healthy individuals remains insufficiently understood. This study investigated the effects of [...] Read more.
Objective: Sodium–glucose cotransporter 2 (SGLT2) inhibitors, particularly empagliflozin, have attracted considerable attention because of their cardiovascular benefits beyond glycemic control. However, the interaction between empagliflozin and exercise-induced physiological cardiac remodeling in healthy individuals remains insufficiently understood. This study investigated the effects of different swimming exercise protocols (anaerobic, aerobic, and endurance), administered alone or in combination with empagliflozin, on cardiac structure and electrophysiology. Methods: Thirty-six male Sprague–Dawley rats were randomly assigned to six groups (n = 6 per group): anaerobic (An), aerobic (Ae), endurance (En), and the corresponding exercise groups combined with empagliflozin (An + Empa, Ae + Empa, and En + Empa). Empagliflozin was administered by oral gavage at a dose of 15 mg/kg/day for 30 days. Transthoracic echocardiography, electrocardiography (ECG), and gastrocnemius electromyography were performed at baseline and at the end of the study to assess cardiac remodeling, heart rate, and neuromuscular function. The study was carried out over a 30-day intervention period following ethics committee approval on 24 July 2024. Results: No significant between-group differences were observed in echocardiographic parameters before the intervention. On day 30, significant differences were identified among the groups in interventricular septal thickness at end-diastole (IVSd) (p = 0.027), left ventricular internal diameter at end-diastole (LVIDd) (p = 0.009), and end-diastolic volume (EDV) (p = 0.014). Bonferroni-corrected post hoc analysis showed that the aerobic exercise plus empagliflozin group differed from several exercise-only groups, particularly in parameters related to ventricular size and filling volume, including LVIDd and EDV (p < 0.008). On day 30, electrocardiographic repolarization-related parameters, including QT, QTc, JT, and Tpeak–Tend intervals, also differed significantly among the groups (all p < 0.05). In post hoc analysis, the anaerobic exercise group showed significant differences in QT and JT intervals compared with the aerobic and endurance groups (p < 0.008). In the anaerobic protocol, empagliflozin was associated with a reduction in heart rate compared with the corresponding control group (p = 0.019). No significant between-group differences were observed in EMG findings. Conclusions: Different exercise protocols induce distinct patterns of adaptation in cardiac structure and electrophysiology in healthy rats. Empagliflozin (15 mg/kg/day) may modulate exercise-induced cardiac responses in a modality-dependent manner; the most pronounced echocardiographic effects were observed in the aerobic protocol, whereas the effect on heart rate was observed in the anaerobic protocol. These findings highlight the need for longer-term and mechanistic studies to further clarify the effects of SGLT2 inhibitors on physiological cardiac remodeling. Full article
(This article belongs to the Section Cardiovascular Medicine)
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13 pages, 860 KB  
Article
Preoperative Transcranial Doppler Findings and Postoperative Delirium After Cardiac Surgery in Elderly Patients: A Prospective Observational Study
by Astrid Bergmann, Yurii Ruzhyn, Jan Wiesemann, Nikolai Hulde, Janis Fliegenschmidt, Alexander Krannich and Vera von Dossow
Life 2026, 16(6), 1026; https://doi.org/10.3390/life16061026 - 19 Jun 2026
Viewed by 175
Abstract
Postoperative delirium (POD) is a common neurocognitive complication after cardiac surgery in elderly patients and is associated with adverse clinical outcomes. Impaired cerebral autoregulation and reduced cerebrovascular reserve may contribute to POD development. Automated transcranial Doppler sonography (TCD) enables non-invasive assessment of intracranial [...] Read more.
Postoperative delirium (POD) is a common neurocognitive complication after cardiac surgery in elderly patients and is associated with adverse clinical outcomes. Impaired cerebral autoregulation and reduced cerebrovascular reserve may contribute to POD development. Automated transcranial Doppler sonography (TCD) enables non-invasive assessment of intracranial hemodynamics and may provide additional information for perioperative risk assessment. In this prospective single-center observational study, 108 patients aged >70 years scheduled for elective cardiac surgery with cardiopulmonary bypass were enrolled. Patients who had pre-existing neurological disease, had a pathological carotid Doppler ultrasound, underwent emergency surgery, or were unable to undergo delirium screening were excluded. Preoperative bilateral TCD of the middle cerebral arteries was performed using an automated WAKIe R3 system. POD was assessed on postoperative days 1–3 using the CAM-ICU. The primary endpoint was the occurrence of POD. Twenty-one patients were excluded, leaving 87 patients for analysis. POD occurred in 14 patients (16%). All patients who developed POD had pathological preoperative TCD findings, whereas no POD occurred among patients with normal TCD examinations. Overall, 82 patients (94%) demonstrated pathological intracranial hemodynamic findings despite normal carotid Doppler ultrasound. In multivariable Firth logistic regression adjusted for age and sex, pathological TCD findings remained associated with POD; however, interpretation was limited by the small number of outcome events and quasi-complete separation. In elderly patients undergoing cardiac surgery with cardiopulmonary bypass, pathological preoperative TCD findings were frequently observed and may be associated with an increased risk of postoperative delirium. The marked discrepancy between normal carotid ultrasound and abnormal intracranial hemodynamics suggests that TCD may provide complementary information regarding cerebrovascular function. Given the limited sample size and event rate, these findings should be considered exploratory and require confirmation in larger multicenter studies. Full article
(This article belongs to the Section Medical Research)
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11 pages, 578 KB  
Brief Report
Comparison of Heart Rate Variability Between Sexes: Impact of a Physically Active Lifestyle
by Reberth Magalhães Da Silva, Ariane Viana, Fernanda Monma, Fernando Alves Santa Rosa, José Robertto Zaffalon and Kátia De Angelis
Int. J. Environ. Res. Public Health 2026, 23(6), 809; https://doi.org/10.3390/ijerph23060809 - 18 Jun 2026
Viewed by 253
Abstract
Sex differences and lifestyle factors such as physical activity play an important role in cardiovascular autonomic regulation. Heart rate variability (HRV) is a widely used marker of cardiac autonomic modulation and cardiovascular health. However, the combined influence of sex and physical activity levels [...] Read more.
Sex differences and lifestyle factors such as physical activity play an important role in cardiovascular autonomic regulation. Heart rate variability (HRV) is a widely used marker of cardiac autonomic modulation and cardiovascular health. However, the combined influence of sex and physical activity levels on HRV in young, healthy adults has not been sufficiently explored. Therefore, this study investigated the effects of sex and a physically active lifestyle on HRV in men and women. A cross-sectional study was conducted on a cohort of young, healthy adults aged 18–30 and categorized into four groups based on: physically active men (AM; n = 37), sedentary men (SM; n = 44), and physically active women (AW; n = 31) and sedentary women (SW; n = 40). Regarding the impact of lifestyle, the AM group exhibited 41% higher total variance (VAR-RR) and 34% higher RMSSD (a parasympathetic index) than the SM group. The AW exhibited 74% and 78% higher VAR-RR and RMSSD, respectively, compared to the SW. Furthermore, the physically active groups (AM and AW) displayed a 75% and 50% lower LF/HF ratio, respectively, compared to their sedentary counterparts. Interestingly, the LF/HF ratio was 66% higher, and the RMSSD was 20% lower in the AM group than in the AW group. HRV indices demonstrated large to very large effect sizes. In conclusion, these findings demonstrate significantly advantage in cardiac autonomic modulation among physically active individuals and women. Together, these results reinforce the roles of female sex and an active lifestyle as important protective factors for cardiovascular health. Full article
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23 pages, 1367 KB  
Article
The Effect of Physical Activity on Heart Structure and Function in African University Students: A Comparative Cross-Sectional Study
by Yaw Amo Wiafe, Collins Kokuro, Gordon Manu Amponsah, Prince Nyansah Adotey, Eugene Osei Amaniampong Buadee and Isaac Kofi Owusu
Hearts 2026, 7(2), 19; https://doi.org/10.3390/hearts7020019 - 17 Jun 2026
Viewed by 183
Abstract
Background: Regular physical activity induces physiological cardiac remodeling (“athlete’s heart”), which may overlap with pathological hypertrophy. Regional echocardiographic and electrocardiographic data among young African adults are limited. This study evaluated how graded physical activity relates to cardiac structure and function among university [...] Read more.
Background: Regular physical activity induces physiological cardiac remodeling (“athlete’s heart”), which may overlap with pathological hypertrophy. Regional echocardiographic and electrocardiographic data among young African adults are limited. This study evaluated how graded physical activity relates to cardiac structure and function among university students in Ghana. Methods: In this comparative cross-sectional study, 174 apparently healthy students aged 18–30 years were categorized into four physical activity groups in the preceding six months: level 1, no regular exercise (n = 29, 16.7%); level 2, <30 min/day of exercise (n = 41, 23.6%); level 3, 30 to 60 min/day of moderate exercise (n = 29, 16.7%); and level 4, >1 h/day of vigorous exercise (n = 75, 43.1%). Anthropometry, blood pressure, 12-lead electrocardiography, and comprehensive transthoracic echocardiography were obtained. Cardiac indices were compared across activity levels using the Kruskal–Wallis or Welch’s ANOVA test, with post hoc comparisons and regression analyses performed where appropriate. Results: Participants were predominantly male (56.3%), with a mean age of 22.3 ± 3.50 years, BMI of 23.0 ± 4.39 kg/m2, systolic blood pressure of 118 ± 13.0 mmHg, diastolic blood pressure of 71.3 ± 9.11 mmHg, and heart rate of 66.9 ± 10.9 bpm. Compared with sedentary participants, those in level 4 had a higher IVSd (9.87 ± 1.61 vs. 8.17 ± 1.47 mm, p < 0.001), LVIDd (43.6 ± 6.96 vs. 40.2 ± 3.58 mm, p = 0.002), LVPWd (10.1 ± 1.95 vs. 8.91 ± 1.60 mm, p = 0.003), and LVM (54.6 ± 7.45 vs. 47.1 ± 6.57 g, p < 0.001). EDV and ESV also increased with activity (90.1 ± 24.8 vs. 69.7 ± 17.8 mL, p < 0.001; 32.4 ± 12.8 vs. 25.6 ± 6.52 mL, p = 0.023). Systolic function was preserved across groups, with an EF of 59.3 ± 4.86% in level 4 vs. 58.3 ± 5.34% in level 1 (p = 0.707). Level 4 participants had a higher SV (57.6 ± 16.7 vs. 46.3 ± 10.4 mL, p = 0.003), CO (3.83 ± 1.17 vs. 3.05 ± 0.70 L/min, p = 0.022), and CI (2.19 ± 0.66 vs. 1.77 ± 0.37 L/min/m2, p = 0.015). Bradycardia was most frequent in level 4 (35.8% vs. 18.2% in level 1, p = 0.041), and PR interval was longer in participants exercising ≥30 min/day than in those exercising <30 min/day (166 ± 23.2 vs. 162 ± 21.8 ms, p = 0.031). Conclusions: In young African university students, greater physical activity was associated with mild physiological remodeling, including a higher left ventricular wall thickness, cavity size, and mass, while systolic and diastolic indices remained preserved. The mean values in the most active group were 9.87 mm IVSd and 10.1 mm LVPWd with preserved EF, supporting activity-related adaptation rather than overt pathological hypertrophy and highlighting the need for population-specific cardiovascular interpretation. Full article
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14 pages, 1823 KB  
Article
Inflammatory Biomarkers and Their Associations with Arrhythmic Burden Following SGLT2-I Treatment in Chronic Heart Failure—A Subanalysis of the ERASe Trial
by Martin Benedikt, Markus Herrmann, Faisal Aziz, Norbert J. Tripolt, Peter Pferschy, Martin Manninger, Markus Wallner, Raffaela Planka, Andreas Zirlik, Harald Sourij, Abderrahim Oulhaj, Markus Stühlinger, Daniel Scherr and Dirk von Lewinski
J. Clin. Med. 2026, 15(12), 4681; https://doi.org/10.3390/jcm15124681 - 17 Jun 2026
Viewed by 190
Abstract
Background: Sodium glucose-linked transport 2 inhibitors (SGLT2-Is) are well known to exert beneficial effects in chronic heart failure (CHF) independent of left ventricular ejection fraction (LVEF). As inflammation plays a key role in cardiac diseases, data on the association of inflammatory biomarkers [...] Read more.
Background: Sodium glucose-linked transport 2 inhibitors (SGLT2-Is) are well known to exert beneficial effects in chronic heart failure (CHF) independent of left ventricular ejection fraction (LVEF). As inflammation plays a key role in cardiac diseases, data on the association of inflammatory biomarkers and ventricular arrhythmic (VA) burden in SGLT2-I-treated patients is lacking. Methods: This pre-defined subanalysis investigated changes in pre-specified inflammatory biomarkers from baseline to week 52 in response to 5 mg Ertugliflozin compared to placebo and their associations to the incidence of VA burden. Results: A total of 36 patients (18 versus 18) with available biobank samples were included in the analysis. At week 52, leukocyte and neutrophil counts, as well as high-sensitive C-reactive protein (hsCRP) and interleukin-6 (IL-6), were numerically higher in the Ertugliflozin group. In contrast, neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) were lower in the Ertugliflozin group, although these differences did not reach statistical significance. Notably, lymphocyte counts were significantly higher in Ertugliflozin showing a mean difference of 19.0 ± 10.78% (p = 0.028). Further, a significantly higher incidence of VA burden was observed among Ertugliflozin-treated patients with elevated hsCRP levels (incidence rate ratio [IRR] 3.58; 95% Confidence interval [CI], 1.12–11.40, p = 0.031). Conclusions: In patients with CHF, Ertugliflozin treatment was associated with a higher incidence of VA burden in those with elevated hsCRP levels. This may suggest a potential higher risk for VA in SGLT2-I-treated patients in the setting of heightened inflammatory activity. However, this finding is based on a single interaction analysis in a small sample size, and the results should therefore be considered exploratory and hypothesis-generating, and must be interpreted cautiously. Full article
(This article belongs to the Special Issue Clinical Aspects of Cardiac Arrhythmias and Arrhythmogenic Disorders)
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2 pages, 154 KB  
Abstract
Probing the In Vivo Physiology and Behaviour of the Atlantic Bluefin Tuna
by David J. McKenzie
Proceedings 2026, 146(1), 10; https://doi.org/10.3390/proceedings2026146010 - 16 Jun 2026
Viewed by 74
Abstract
Introduction: The Atlantic bluefin tuna Thunnus thynnus (ABFT) is a large pelagic apex predator with adaptations for a life of ceaseless swimming during long-distance oceanic migrations. The environmental physiology and energetics of tunas have interested researchers for many decades, but they are [...] Read more.
Introduction: The Atlantic bluefin tuna Thunnus thynnus (ABFT) is a large pelagic apex predator with adaptations for a life of ceaseless swimming during long-distance oceanic migrations. The environmental physiology and energetics of tunas have interested researchers for many decades, but they are notoriously challenging to study because they are so difficult to keep in captivity. Adult ABFT are, however, now fattened in cages at various sites in the Mediterranean, while juveniles are reared from hatching every year at the Unique Scientific and Technological Infrastructure for ABFT aquaculture (ICAR-IEO), near Cartagena in Spain. These facilities provide access to animals, but the fish remain very problematic to study because of their highly active but physiologically delicate nature and, for adults, their very large sizes. Objective: To study the in vivo physiology and behaviour of ABFT. Methodology: We used heart rate biologging and high residency acoustic tracking to follow cardiac and swimming activity over a year in n = 24 adult ABFT (mass range 25 to 200 kg) held in a cage off the coast of Malta (Malta Fish Farming). We then performed swim tunnel respirometry on young of the year juveniles (500g) at ICRA-IEO, but subsequently took a ‘hands-off’ approach, using video analyses and group respirometry on free-swimming animals. Results: The descriptive approach on the caged adults provided understanding of how seasonal water temperatures (15 to 28 °C) affect tuna physiology and behaviour. The swimming respirometry on juveniles revealed that their performance was constrained by confinement in the tunnel, compared to when they were swimming at their spontaneous preferred speed in their rearing tank. Video analyses provided insights into the effects of size (25 to 200 cm bodylength) on spontaneous swimming speeds and coupled with tank respirometry, revealed how progressive hypoxia affects the metabolic rate and schooling behaviour of juveniles. Conclusions: These opportunistic and disparate pieces of information are nonetheless valuable for such a fascinating but data-deficient species, and can be useful in mechanistic models for management of an extremely valuable fishery in a context of global change. Full article
(This article belongs to the Proceedings of The XI Iberian Congress of Ichthyology)
11 pages, 380 KB  
Article
Frailty and Echocardiographic Indices of Diastolic Function in Older Adults: A Cross-Sectional Analysis
by Dimitrios Anagnostou, Georgia Vamvakou, Zoi Kollia, Christos Chitas, Nikolaos Theodorakis, Sofia Kalantzi, Aikaterini Spyridaki, Vassilis Milionis, Michalitsa Christodoulou, Ioanna Nella, Efi Gourzoulidou, Sofia Athinaiou, Gesthimani Triantafylli and Maria Nikolaou
J. Clin. Med. 2026, 15(12), 4645; https://doi.org/10.3390/jcm15124645 - 15 Jun 2026
Viewed by 134
Abstract
Background: Frailty in older adults is linked to adverse cardiovascular outcomes, but its relationship with echocardiographic markers of diastolic function remains unclear. We examined associations between frailty measures and indices of diastolic function in community-dwelling older adults. Methods: This cross-sectional study [...] Read more.
Background: Frailty in older adults is linked to adverse cardiovascular outcomes, but its relationship with echocardiographic markers of diastolic function remains unclear. We examined associations between frailty measures and indices of diastolic function in community-dwelling older adults. Methods: This cross-sectional study included 537 adults aged ≥65 years from a multidisciplinary outpatient clinic. Frailty was assessed using the Fried phenotype, Clinical Frailty Scale (CFS), gait speed, and handgrip strength. Associations with diastolic indices were analyzed using multivariable regression with sequential adjustment. Sensitivity analysis was performed via matching. Results: According to the Fried phenotype, 30.8% of participants were robust, 59.7% pre-frail, and 9.5% frail. Indexed left atrial dimension (LAi) was consistently higher in frail individuals. Frailty was also associated with higher odds of elevated right ventricular systolic pressure (>35 mmHg) in unadjusted analyses. Using the CFS, individuals with a score higher than 3 had significantly higher NT-proBNP levels compared to those with a score of 1–2. Higher gait speed and handgrip strength were associated with more favorable cardiac structure, including smaller left heart chamber sizes, and lower natriuretic peptide levels. Conclusions: Frailty was independently associated with structural and functional markers of diastolic dysfunction in older adults, particularly left atrial enlargement (as captured in Fried) and NT-proBNP elevation (as captured in CFS), supporting the integration of frailty assessment into cardiovascular risk evaluation. Full article
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26 pages, 6326 KB  
Article
tsRNA-3025a Impairs Mitochondrial Function and Autophagy to Inhibit Myocardial Regeneration and Repair Following Ischemia–Reperfusion Injury
by Zehao Feng, Xing Li, Ai Zhou, Han Zhang, Kaixuan Tang, Yumo Yang, Ying Chen, Li Zhang and Lingmei Qian
J. Cardiovasc. Dev. Dis. 2026, 13(6), 266; https://doi.org/10.3390/jcdd13060266 - 12 Jun 2026
Viewed by 268
Abstract
Myocardial ischemia–reperfusion (I/R) injury is a frequent complication of acute myocardial infarction (AMI), yet clinical biomarkers and targets remain limited. Although tRNA-derived small RNAs (tsRNAs) are emerging cardiovascular regulators, their roles in I/R injury are not fully elucidated. We identified tsRNA-3025a via sequencing [...] Read more.
Myocardial ischemia–reperfusion (I/R) injury is a frequent complication of acute myocardial infarction (AMI), yet clinical biomarkers and targets remain limited. Although tRNA-derived small RNAs (tsRNAs) are emerging cardiovascular regulators, their roles in I/R injury are not fully elucidated. We identified tsRNA-3025a via sequencing in mouse I/R models and validated its clinical significance. Circulating tsRNA-3025a was significantly upregulated in AMI and unstable angina patients, independently predicting adverse events within 30 days. Functionally, tsRNA-3025a exacerbated apoptosis and mitochondrial dysfunction in vitro, while its in vivo silencing reduced infarct size, improved cardiac function and increased the proportion of Ki67- and pH3-positive cardiomyocytes. Mechanistically, tsRNA-3025a aggravated injury by targeting PIK3C2A, thereby suppressing autophagosome formation and impairing protective autophagic flux during reperfusion. In conclusion, circulating tsRNA-3025a serves as a prognostic biomarker for post-PCI patients. Targeting tsRNA-3025a attenuates myocardial I/R injury and restores myocardial regeneration and repair by regulating PIK3C2A-mediated protective autophagy flux. Full article
(This article belongs to the Section Cardiac Development and Regeneration)
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26 pages, 9577 KB  
Article
Evaluation of a Room-Temperature Preservation Method Maintaining Viability and Function in Human Cardiac Organoids
by Cynthia Van Rompay, Kevin Tabury, Emil Rehnberg, Zoë Janssen, Sarah Baatout, Marianne S. Carlon, Xavier Casadevall i Solvas and Bjorn Baselet
Cells 2026, 15(12), 1065; https://doi.org/10.3390/cells15121065 - 11 Jun 2026
Viewed by 362
Abstract
Three-dimensional (3D) cardiac models, including spheroids, organoids, and organ-on-chips, are advanced systems for studying human physiology, disease, and drug responses with greater biological relevance than 2D models. As their use expands in biomedical research, tissue engineering, and regenerative medicine, reliable preservation methods are [...] Read more.
Three-dimensional (3D) cardiac models, including spheroids, organoids, and organ-on-chips, are advanced systems for studying human physiology, disease, and drug responses with greater biological relevance than 2D models. As their use expands in biomedical research, tissue engineering, and regenerative medicine, reliable preservation methods are needed. However, cryopreservation often fails to protect 3D systems due to limited cryoprotectant penetration, ice formation, and mechanical stress during freezing and thawing. Room-temperature (RT) preservation has emerged as a promising alternative for short-term transport. This study evaluated a RT-based transport medium (CellShip®) for preserving cardiac organoids for up to seven days, compared with conventional cryopreservation using slow-freezing in Cryostor®CS10. Viability and functionality were assessed using apoptosis, ATP levels, beating activity, proliferation, and size. During maturation, organoids showed increased size, ATP levels, and beating capacity. Cryopreservation reduced size, proliferation, ATP levels, and altered beating, while increasing apoptosis. In contrast, RT preservation maintained stable viability and functionality after recovery. These findings demonstrate that RT preservation effectively maintains cardiac organoid integrity and function, offering a promising alternative for short-term storage and transport, with potential terrestrial and nonterrestrial applications. Full article
(This article belongs to the Special Issue 3D Cultures and Organ-on-a-Chip in Cell and Tissue Cultures)
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16 pages, 32374 KB  
Article
Engineering Chimeric Cardio-Vascular Assembloids Using Human iPSC-Derived Cardiomyocytes and Vascular Rings
by Hannah Klör, Kornelia Kenst, Berin Upcin, Süleyman Ergün and Philipp Wörsdörfer
Organoids 2026, 5(2), 18; https://doi.org/10.3390/organoids5020018 - 10 Jun 2026
Viewed by 221
Abstract
The myocardium possesses one of the highest vascular densities in the body. The outermost wall layer of large and medium-sized vessels, the adventitia, forms a critical interface between the vasculature and the myocardium and serves as a reservoir for stem and progenitor cells [...] Read more.
The myocardium possesses one of the highest vascular densities in the body. The outermost wall layer of large and medium-sized vessels, the adventitia, forms a critical interface between the vasculature and the myocardium and serves as a reservoir for stem and progenitor cells capable of differentiating into all vascular wall lineages as well as innate immune cells, including macrophages. Current cardiac organoid models intrinsically develop networks of endothelial cords and small capillary-like structures that resemble cardiac microvessels. However, these microvessels mostly lack an adventitial compartment in vivo. Here, we present a potential alternative assembloid strategy that combines vascular segments from mouse and human origin with either cardiomyocytes or cardiac spheroids derived from human induced pluripotent stem cells, thereby incorporating large diameter vessels and the vascular adventitia into a cardiac tissue model. Within the assembloids, the myocardial component remained contractile and connected to the vascular adventitia, which displayed cellular sprouting toward the hiPSC-derived cardiac tissue. Immunostaining for vascular and immune markers revealed that the adventitia gave rise to endothelial sprouts and macrophage-like cells which integrated into the myocardial tissue. In summary, we present proof of concept for complex assembloids composed of vessel segments and human iPSC-derived cardiomyocytes which contain and maintain an in vivo-like adventitial compartment. We suggest this model may serve as a platform for investigating myocardial–stromal interactions, cardiac tissue repair, and functional remodeling under both physiological and pathological conditions. Furthermore, the incorporation of large-lumen vessel segments may enable future experimental perfusion, rendering the model particularly suitable for drug testing via intravascular delivery. Full article
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15 pages, 2238 KB  
Systematic Review
The Effectiveness of Methylene Blue in Adult Shock: A Systematic Review, Meta-Analysis, and Trial Sequential Analysis of Randomized Controlled Trials
by David Rene Rodríguez-Lima, Adelaida Rodríguez-Villegas, Juan Diego Toro Egas and Esther María Campo Bautista
J. Clin. Med. 2026, 15(12), 4481; https://doi.org/10.3390/jcm15124481 - 10 Jun 2026
Viewed by 244
Abstract
Background/Objectives: Methylene blue (MB) has re-emerged as an adjunctive vasopressor-sparing therapy in vasoplegic shock states, with emerging evidence supporting its hemodynamic benefits; however, its effect on mortality remains uncertain. We systematically evaluated the effectiveness of MB versus standard therapy in adults with circulatory [...] Read more.
Background/Objectives: Methylene blue (MB) has re-emerged as an adjunctive vasopressor-sparing therapy in vasoplegic shock states, with emerging evidence supporting its hemodynamic benefits; however, its effect on mortality remains uncertain. We systematically evaluated the effectiveness of MB versus standard therapy in adults with circulatory shock. Methods: We performed a systematic review and meta-analysis of randomized controlled trials registered in PROSPERO (CRD420261326534) and reported according to PRISMA. MEDLINE, Embase, and the Cochrane Library were searched through February 2026. An additional AI-assisted supplementary search was conducted to minimize the risk of missing eligible studies. Eligible studies enrolled adults with shock and compared MB with standard therapy or placebo. The primary outcome was 28–30-day all-cause mortality. Secondary outcomes were renal replacement therapy (RRT), hospital length of stay, and intensive care unit (ICU) length of stay. Risk of bias was assessed with RoB 2. Results: Nine randomized trials involving 535 participants met the eligibility criteria; most evaluated septic shock, while one trial included post-cardiac surgery vasoplegic shock. Eight trials contributed to the quantitative synthesis of mortality. MB was not associated with a statistically significant reduction in short-term mortality. Secondary analyses also did not demonstrate significant pooled effects for RRT, hospital length of stay, or ICU length of stay, although several individual trials reported faster hemodynamic improvement and reduced vasopressor exposure with MB. Overall confidence in the pooled estimates was limited by small sample sizes, clinical heterogeneity, imprecision, and risk-of-bias concerns in some studies. Conclusions: Current randomized evidence does not demonstrate a clear mortality or resource use benefit of MB in adult shock, despite signals of hemodynamic improvement. MB appears promising as an adjunctive therapy, but adequately powered, methodologically rigorous trials are required before its routine early use can be recommended. Full article
(This article belongs to the Section Cardiovascular Medicine)
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28 pages, 35122 KB  
Article
The ezrin Gene Regulates Early Cardiac Morphogenesis and Contractile Function in Zebrafish Through the Coordinated Regulation of Apoptosis, Calcium Homeostasis, and the MAPK Signaling Pathway
by Jinrui Lv, Ting Zeng, Beiya Liao, Ling Liu, Lei Xiong, Hao Xie, Lin Zhu, Xingzi Jiang, Zhuchuyu Zhong and Huaping Xie
Cells 2026, 15(12), 1046; https://doi.org/10.3390/cells15121046 - 7 Jun 2026
Viewed by 346
Abstract
Ezrin, expressed by the EZR gene, is a member of the ERM protein family that connects the plasma membrane to the actin cytoskeleton, participating in processes such as cell adhesion, migration, and signaling. However, its role in cardiac morphogenesis remains incompletely understood. In [...] Read more.
Ezrin, expressed by the EZR gene, is a member of the ERM protein family that connects the plasma membrane to the actin cytoskeleton, participating in processes such as cell adhesion, migration, and signaling. However, its role in cardiac morphogenesis remains incompletely understood. In zebrafish (Danio rerio), two ezrin homologs, ezra and ezrb, are present. CRISPR/Cas9 gene editing technology was used to generate ezra knockout lines, and the simultaneous knockdown of ezra and ezrb was induced via morpholino oligonucleotides (MOs). To investigate the molecular mechanisms, transcriptome sequencing and bioinformatic analysis were conducted on 48 h post-fertilization (hpf) ezrin–MO embryos, with subsequent validation using a real-time quantitative polymerase chain reaction (RT-qPCR) and whole-mount in situ hybridization (WISH) experiment. The results showed that ezra−/− exhibited a compensatory upregulation of ezrb without overt developmental defects, whereas ezrin–MO embryos presented with pericardial edema, reduced cardiac chamber size, and atrioventricular valve malformations at 48 hpf. RNA-seq revealed that myocardial contraction-related genes were significantly dysregulated and apoptotic signaling pathways were activated in ezrin–MO embryos. These findings demonstrate that ezra and ezrb are functionally redundant in cardiac development and that the loss of ezrin function may lead to cardiac developmental defects and impaired myocardial contractility via the activation of apoptotic signaling pathways. Full article
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33 pages, 5647 KB  
Article
Integration of Machine Learning Techniques in ECG-Based Multiclass Arrhythmia Classification with Explainability Analysis
by Abdullah, Zulaikha Fatima, Abdollah Abadian, Carlos Guzmán Sánchez Mejorada, Miguel Jesús Torres Ruiz and Rolando Quintero Téllez
Biosensors 2026, 16(6), 326; https://doi.org/10.3390/bios16060326 - 3 Jun 2026
Viewed by 612
Abstract
Electrocardiogram (ECG) analysis is a cornerstone non-invasive diagnostic technique for detecting cardiac arrhythmias, which remain a leading cause of mortality worldwide. While recent advances in deep learning have significantly improved automated arrhythmia classification, the current literature lacks systematic, fair comparisons of fundamental neural [...] Read more.
Electrocardiogram (ECG) analysis is a cornerstone non-invasive diagnostic technique for detecting cardiac arrhythmias, which remain a leading cause of mortality worldwide. While recent advances in deep learning have significantly improved automated arrhythmia classification, the current literature lacks systematic, fair comparisons of fundamental neural architectures under unified experimental conditions, and very few studies provide model interpretability. This study addresses these gaps by first providing a rigorous comparative analysis of three representative architectures—Artificial Neural Network (ANN), Convolutional Neural Network (CNN), and Residual Network (ResNet)—on the MIT-BIH Arrhythmia Database under identical preprocessing, training, and evaluation protocols. We then propose an efficient Fine-Tuned CNN (FT-CNN) optimized for ECG signal characteristics through adaptive kernel sizing for P-QRS-T morphological extraction, multi-faceted regularization including L2, dropout, and batch normalization, cosine annealing learning rate, and a custom loss function combining weighted categorical cross-entropy with focal loss with gamma equal to 2.0 to address severe class imbalance. The FT-CNN achieves an accuracy of 98.51%, outperforming fourteen benchmark models, including standard CNN with an accuracy of 97.20%, ResNet with 96.88%, LSTM with 96.50%, GRU with 96.30%, and traditional classifiers. Comprehensive ablation studies confirm an improvement of 6.17% over the baseline. Class-wise analysis reveals excellent performance for normal beats with an F1-score of 0.99, ventricular ectopic beats with 0.95, and unknown beats with 0.98, while supraventricular ectopic beats with an F1-score of 0.79 and fusion beats with 0.70 remain challenging. Unlike most prior works, we integrate Grad-CAM and Integrated Gradients for explainability, quantitatively evaluating attribution faithfulness, sanity checks, and noise robustness. Full article
(This article belongs to the Special Issue Biosensors for Physiological Signal Monitoring)
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31 pages, 9659 KB  
Systematic Review
Prognostic Role of Left Atrial Reservoir Strain for Risk Stratification in Aortic Stenosis: A Systematic Review
by Andrea Sonaglioni, Massimo Baravelli, Giulio Francesco Gramaglia, Gian Luigi Nicolosi and Michele Lombardo
J. Clin. Med. 2026, 15(11), 4304; https://doi.org/10.3390/jcm15114304 - 2 Jun 2026
Viewed by 368
Abstract
Background: Risk stratification in aortic stenosis (AS) remains challenging, particularly in patients with preserved left ventricular ejection fraction or inconclusive symptom status, as conventional parameters primarily reflect valvular obstruction and may underestimate the extent of cardiac dysfunction. Left atrial reservoir strain (LASr) has [...] Read more.
Background: Risk stratification in aortic stenosis (AS) remains challenging, particularly in patients with preserved left ventricular ejection fraction or inconclusive symptom status, as conventional parameters primarily reflect valvular obstruction and may underestimate the extent of cardiac dysfunction. Left atrial reservoir strain (LASr) has emerged as a promising and potentially more comprehensive marker of atrial function and diastolic burden, with potential prognostic implications. Methods: A systematic review was conducted in accordance with PRISMA guidelines. PubMed, Scopus, and EMBASE were searched from inception to April 2026. Studies including adult patients with moderate or severe AS and evaluating LASr using different imaging modalities (speckle-tracking echocardiography, cardiac computed tomography, or cardiac magnetic resonance) were considered eligible if clinical outcomes were reported. Data were qualitatively synthesized, and continuous variables were summarized as weighted medians with interquartile ranges. Results: Twenty-one studies were included, encompassing a large and clinically heterogeneous population. During follow-up, a substantial proportion of patients experienced adverse events, including mortality, heart failure hospitalization, arrhythmic events, and composite cardiovascular outcomes. Across studies, reduced LASr consistently emerged as a significant predictor of adverse outcomes. This association was observed both when LASr was analyzed as a continuous variable and when defined using study-specific cut-off values, which generally clustered within a relatively narrow range. Importantly, LASr demonstrated incremental prognostic value beyond conventional echocardiographic parameters, including left atrial size, left ventricular ejection fraction, global longitudinal strain, and indices of diastolic dysfunction. The prognostic relevance of LASr was consistent across different imaging modalities, including both echocardiography and cardiac computed tomography (with no eligible studies using cardiac magnetic resonance). Conclusions: LASr is a robust and reproducible marker of adverse prognosis in patients with AS, reflecting the cumulative burden of left-sided pressure overload and atrial remodeling. Its integration into multiparametric assessment may enhance risk stratification and support more individualized clinical decision-making. Further prospective studies are warranted to standardize measurement techniques and define clinically actionable thresholds. Full article
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