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16 pages, 720 KB  
Article
Prevalence of rs850683722 Variant and Its Influence on the Course of Myxomatous Mitral Valve Disease in 105 Cavalier King Charles Spaniel Dogs in the Polish Population
by Maksymilian Lewicki, Sylwia Barbara Górczyńska-Kosiorz, Justyn Gach, Piotr Frydrychowski, Zuzanna Wojtczak and Agnieszka Noszczyk-Nowak
Animals 2026, 16(13), 1956; https://doi.org/10.3390/ani16131956 (registering DOI) - 24 Jun 2026
Abstract
Myxomatous mitral valve disease (MMVD) is the most common acquired cardiac disease in small-breed dogs and shows particularly high prevalence and early onset in Cavalier King Charles Spaniels (CKCS). Although MMVD is considered a complex, polygenic disease, the clinical relevance of individual genetic [...] Read more.
Myxomatous mitral valve disease (MMVD) is the most common acquired cardiac disease in small-breed dogs and shows particularly high prevalence and early onset in Cavalier King Charles Spaniels (CKCS). Although MMVD is considered a complex, polygenic disease, the clinical relevance of individual genetic variants remains incompletely understood. The angiotensin-converting enzyme (ACE) gene variant rs850683722 has previously been associated with altered ACE activity and differences in renin–angiotensin–aldosterone system-related responses in dogs with MMVD. The aim of this study was to determine the prevalence of rs850683722 in a Polish population of CKCS dogs and to assess whether this variant is associated with the clinical course of MMVD. A total of 105 CKCS dogs were included in the study. All dogs underwent standardized cardiovascular evaluation, including echocardiography, electrocardiography, and systolic blood pressure measurement. MMVD diagnosis and staging were performed according to current ACVIM consensus criteria. Genotyping of the rs850683722 variant was performed using Sanger sequencing for 95 dogs, while next-generation sequencing data was obtained for 10 dogs. Genotype distribution, allele frequencies, conformity with the Hardy–Weinberg equilibrium (HWE), sex-related differences, and associations between genotype and age at progression to selected MMVD stages or the primary clinical endpoint were assessed statistically. The most frequent genotype was AA, detected in fifty-nine dogs, followed by GG in thirty-seven dogs and AG in nine dogs. When dogs carrying at least one A allele were considered variant-positive, the overall prevalence of the variant-positive genotype was 64.8%. The calculated allele frequencies were 0.605 for the A allele and 0.395 for the G allele. The observed genotype distribution deviated markedly from the Hardy–Weinberg equilibrium, mainly because of a pronounced deficit of heterozygous dogs. No significant association was detected between genotype and sex. Genotype was also not significantly associated with age at progression to stage B2 or stage C. A statistically significant difference in age of death was demonstrated by genotype, but this difference was not reflected in the survival analysis. The rs850683722 variant was highly prevalent in the studied Polish CKCS population, with a frequency comparable to previously reported data for this breed. Despite its documented biological association with ACE activity and RAAS-related responses, the variant was not significantly associated with the clinical progression of MMVD in this cohort. These findings suggest that rs850683722 alone seems unlikely to be a reliable marker for predicting the severity or rate of MMVD progression in Polish CKCS dogs. Further studies including larger cohorts, longer follow-up, pedigree information, and the direct assessment of RAAS activity may help clarify whether this variant has stage-dependent or treatment-related clinical relevance. Full article
(This article belongs to the Section Veterinary Clinical Studies)
27 pages, 4931 KB  
Article
Millimeter-Wave Radar-Based ECG Reconstruction Using Respiratory Harmonic Suppression and CA-WTBNet
by Bowen Xiao, Chuyi Zhou, Lu Wang, Caiping Song and Yong Jia
Bioengineering 2026, 13(7), 731; https://doi.org/10.3390/bioengineering13070731 (registering DOI) - 24 Jun 2026
Abstract
Millimeter-wave radar enables non-contact monitoring of cardiac activity and therefore has the potential to reconstruct electrocardiogram signals without surface electrodes. However, existing radar-based electrocardiogram reconstruction methods still suffer from incomplete extraction of heartbeat-related information and insufficient modeling of electrocardiogram-related features, which limits reconstruction [...] Read more.
Millimeter-wave radar enables non-contact monitoring of cardiac activity and therefore has the potential to reconstruct electrocardiogram signals without surface electrodes. However, existing radar-based electrocardiogram reconstruction methods still suffer from incomplete extraction of heartbeat-related information and insufficient modeling of electrocardiogram-related features, which limits reconstruction accuracy. To address these issues, this study proposes a millimeter-wave radar-based electrocardiogram reconstruction method that integrates a respiratory-harmonic-suppressed multi-channel signal-processing frontend with the proposed CA-WTBNet deep reconstruction network. First, based on maximal overlap discrete wavelet transform-based multi-resolution analysis, respiratory harmonics mixed into heartbeat-related components are suppressed by combining respiratory harmonic detection with a heart-rate frequency protection strategy, while cardiac-related information is preserved as much as possible. A multi-channel input representation is then constructed. Meanwhile, the proposed deep reconstruction network is developed to jointly model complementary channel-wise features, local waveform morphology, and temporal dependencies by integrating channel-attention mechanisms, convolutional residual modules, window-based Transformer blocks, and bidirectional long short-term memory. Experiments conducted on the public dataset show that our method achieves an average Pearson correlation coefficient of 0.9641, a mean normalized root mean square error of 0.0458, an average R-peak F1 score of 0.9956, and an average R-peak timing error of 3.13 ms on the test set. In comparison with related studies on the same public Resting dataset, the proposed method achieves the best overall performance among the compared methods, with a 0.53% improvement in Pearson correlation coefficient and a 10.20% reduction in normalized root mean square error over the best-performing compared method. Full article
(This article belongs to the Section Biosignal Processing)
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14 pages, 268 KB  
Article
Cardiopulmonary Exercise Testing in Elderly Patients with Cardiopulmonary Comorbidities: Safety and Clinical Feasibility
by Miraç Öz Kahya, Mursal Isgenderli, Ömer Faruk Tüten and Öznur Yıldız
J. Clin. Med. 2026, 15(13), 4896; https://doi.org/10.3390/jcm15134896 (registering DOI) - 24 Jun 2026
Abstract
Background/Objectives: Cardiopulmonary exercise testing (CPET) provides an integrated assessment of cardiovascular, respiratory, and metabolic responses during exercise. Although CPET is increasingly used in older adults for preoperative physiological evaluation and assessment of exercise limitation, evidence regarding its safety and clinical feasibility in [...] Read more.
Background/Objectives: Cardiopulmonary exercise testing (CPET) provides an integrated assessment of cardiovascular, respiratory, and metabolic responses during exercise. Although CPET is increasingly used in older adults for preoperative physiological evaluation and assessment of exercise limitation, evidence regarding its safety and clinical feasibility in elderly patients with mixed cardiopulmonary comorbidities remains limited. Methods: In this retrospective observational study, we evaluated 235 consecutive patients who underwent CPET at a tertiary referral center. Patients were categorized into two groups according to age: ≥65 years and <65 years. Clinical characteristics, pulmonary function parameters, CPET findings, feasibility outcomes, and adverse events during testing were analyzed. Results: A total of 235 patients were included, with a mean age of 62.3 ± 12.8 years. Among them, 112 (47.6%) patients were aged ≥65 years and 35 (14.8%) were aged ≥75 years. Comorbidities were present in 170 patients, with hypertension being the most common. The leading indication for CPET was preoperative evaluation prior to thoracic surgery. Most elderly patients successfully completed CPET and provided clinically interpretable physiological data. In the ≥65 years group, CPET was terminated prematurely in 10 patients due to syncope, severe dyspnea, bronchospasm, chest pain, or arrhythmia. In the ≥65 years group, exercise-induced desaturation occurred in 24 patients; the lowest recorded oxygen saturation was 84%, and no desaturation episode required premature termination of the test. No major complications, deaths, myocardial infarctions, or cardiac arrests were observed during CPET or within the subsequent three days. No statistically significant differences in adverse event rates were observed between the age groups. Univariate logistic regression analysis demonstrated that lower FEV1 % predicted and lower FEV1/FVC % predicted ratio were associated with clinically significant adverse events in elderly patients [OR (95% CI): 0.96 (0.94–0.99), p = 0.02, OR (95% CI): 0.90 (0.84–0.96), p = 0.001, respectively]. Conclusions: CPET was feasible in the majority of elderly patients with cardiopulmonary comorbidities, with most individuals successfully completing testing and providing clinically interpretable physiological data. No major complications were observed in this cohort. These findings suggest that, when performed under appropriate supervision and careful patient selection, CPET may represent a practical tool for functional assessment and preoperative physiological evaluation in older adults. Larger prospective multicenter studies are warranted to further define its safety and feasibility in this population. Full article
(This article belongs to the Section Geriatric Medicine)
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17 pages, 560 KB  
Article
Real-World Tumor-Infiltrating Lymphocyte Therapy for Metastatic Melanoma: Treatment Delivery, Immune Reconstitution, and Cardiac Monitoring During High-Dose IL-2
by Mohamed A. Aboelatta, Jabra Zarka, Nika Tchatchua, Noureldin A. Aboelatta, Jeffrey E. Johnson, James W. Jakub, Justin Desroches, Justine Wilson-Miller, Anthony Tabiim, Deepti Behl, Heather N. Montane, Lisa A. Kottschade, Anastasios Dimou, Matthew S. Block, Elisabeth I. Heath, Bently Doonan, Mahesh Seetharam, Julian R. Molina, Jonathan E. Charnin, Paula Gill, Yi Lin, Binav Baral, Svetomir N. Markovic and Arkadiusz Z. Dudekadd Show full author list remove Hide full author list
Curr. Oncol. 2026, 33(7), 379; https://doi.org/10.3390/curroncol33070379 (registering DOI) - 24 Jun 2026
Abstract
Background/Objectives: Tumor-infiltrating lymphocyte (TIL) therapy is an important option for patients with metastatic melanoma progressing after standard systemic therapy, but real-world data on treatment delivery, toxicity monitoring, and immune recovery remain limited. We evaluated clinical outcomes, treatment tolerance, immune reconstitution, and cardiac biomarker [...] Read more.
Background/Objectives: Tumor-infiltrating lymphocyte (TIL) therapy is an important option for patients with metastatic melanoma progressing after standard systemic therapy, but real-world data on treatment delivery, toxicity monitoring, and immune recovery remain limited. We evaluated clinical outcomes, treatment tolerance, immune reconstitution, and cardiac biomarker dynamics across three Mayo Clinic sites. Methods: We retrospectively analyzed adults with metastatic melanoma who received lymphodepleting chemotherapy followed by TIL infusion and high-dose interleukin-2 (IL-2) between April 2024 and December 2025. Clinical outcomes, treatment delivery, and adverse events were assessed. Longitudinal immune monitoring included CD4 and CD8 T-cell counts, CD4:CD8 ratio, and immunoglobulin G (IgG) at baseline and follow-up. In a prespecified cardiac sub-cohort, high-sensitivity troponin (hs-Tn) was measured during IL-2 administration to evaluate associations with cardiac events and IL-2 interruption. Results: Thirty-six patients underwent TIL infusion. The objective response rate was 50.0%, including complete responses in 13.9%, and the disease control rate was 72.2%. Median progression-free survival was 3.61 months, and median overall survival was 12.94 months. M1d disease was associated with inferior overall survival on univariable analysis (HR 6.55, 95% CI 2.03–21.17; p = 0.002), with attenuation after multivariable adjustment. Receipt of ≥3 IL-2 doses was associated with longer overall survival on univariable analysis (HR 0.20, 95% CI 0.06–0.64; p = 0.007), but this association also attenuated after adjustment. Longitudinal immune monitoring demonstrated persistent CD4 lymphopenia through 6 months, sustained inversion of the CD4:CD8 ratio, and declining IgG at months 3 and 6. In the cardiac sub-cohort (24 patients; 87 IL-2 doses), post-dose hs-Tn ≥15 ng/L was associated with clinically significant cardiac events (OR 9.6, 95% CI 1.5–60.6; p = 0.016) and IL-2 interruption (OR 3.4, 95% CI 1.1–10.7; p = 0.036). For cardiac events, hs-Tn ≥15 ng/L had 100% sensitivity and 100% negative predictive value. Conclusions: In routine practice, TIL therapy was feasible and active in metastatic melanoma. M1d disease identified a subgroup with poor survival, peri-dose hs-Tn showed promise as a tool to support safer IL-2 delivery, and prolonged CD4 suppression with IgG decline suggests that recovery after TIL therapy extends beyond initial hematologic reconstitution. These findings support prospective validation of biomarker-guided IL-2 monitoring and extended post-treatment immune surveillance. Full article
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24 pages, 2334 KB  
Review
Impact of CaV1.3 L-Type Calcium Channels on Arrhythmogenesis in Cancer
by Lianlen Joy Go Distor, Yvonne Sleiman, Jean-Baptiste Reisqs, Vamsi Krishna Murthy Ginjupalli, Michael Cupelli and Mohamed Boutjdir
Int. J. Mol. Sci. 2026, 27(13), 5663; https://doi.org/10.3390/ijms27135663 (registering DOI) - 23 Jun 2026
Abstract
Cardiovascular disease and cancer remain the leading causes of death worldwide. Although numerous cancer therapies have improved survival rates, they also increase the risk of cardiomyopathy, heart failure, and arrhythmias. These cardiovascular complications can limit treatment options and adversely affect the long-term quality [...] Read more.
Cardiovascular disease and cancer remain the leading causes of death worldwide. Although numerous cancer therapies have improved survival rates, they also increase the risk of cardiomyopathy, heart failure, and arrhythmias. These cardiovascular complications can limit treatment options and adversely affect the long-term quality of life of cancer survivors. CaV1.3, an L-type calcium channel encoded by CACNA1D, emerges as a central molecular mediator linking cardiovascular disease and cancer. It regulates calcium entry into cardiomyocytes and contributes to sinoatrial pacemaking and atrioventricular conduction. It also contributes to proliferation, migration, and therapy resistance in several cancers. Chemotherapy-induced oxidative stress, inflammatory signaling, hypoxia, and transcriptional changes can modulate the expression, gating, splicing, and trafficking of CaV1.3 channels. All these changes destabilize diastolic depolarization and impair conduction, thereby promoting arrhythmias in cancer patients. This review focuses on CaV1.3 biology in cardio-oncology, along with the mechanisms of chemotherapy-induced cardiotoxicity. It outlines the role of CaV1.3 as a key mediator linking cancer therapies to subsequent nodal dysfunction and increased arrhythmia susceptibility. It also expands on how patient-specific induced pluripotent stem cell-derived cardiomyocytes can model CaV1.3 dysregulation as well as support the development of targeted therapies. We propose that CaV1.3 represents a mechanistic bridge linking cancer therapy, calcium signaling, and cardiac electrophysiology, and that elucidating its pathophysiology may guide the design of targeted strategies in cardio-oncology. Full article
(This article belongs to the Section Molecular Biology)
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11 pages, 361 KB  
Article
Association of Serial Lactate-to-Albumin and C-Reactive Protein-to-Albumin Ratios with In-Hospital Mortality After Out-of-Hospital Cardiac Arrest
by Wan Young Heo, Dong Hun Lee, Seok Jin Ryu, Byung Kook Lee, Yong Hun Jung and Kyung Woon Jeung
J. Clin. Med. 2026, 15(13), 4851; https://doi.org/10.3390/jcm15134851 (registering DOI) - 23 Jun 2026
Viewed by 47
Abstract
Background: The lactate-to-albumin ratio (LAR) and C-reactive protein-to-albumin ratio (CAR) are biomarkers for metabolic stress and inflammation. However, their prognostic significance after return of spontaneous circulation (ROSC) in out-of-hospital cardiac arrest (OHCA) remains unclear. Therefore, this study aims to investigate the association [...] Read more.
Background: The lactate-to-albumin ratio (LAR) and C-reactive protein-to-albumin ratio (CAR) are biomarkers for metabolic stress and inflammation. However, their prognostic significance after return of spontaneous circulation (ROSC) in out-of-hospital cardiac arrest (OHCA) remains unclear. Therefore, this study aims to investigate the association between serial LAR/CAR measurements and in-hospital mortality. Methods: This retrospective observational cohort study included adult comatose patients with OHCA treated with targeted temperature management between January 2022 and December 2025. Serum lactate, albumin, and C-reactive protein levels were measured at admission and at 24, 48, and 72 h after ROSC. The primary outcome was in-hospital mortality. Multivariable logistic regression analyses were performed to assess independent associations of LAR and CAR with in-hospital mortality, and discriminatory performance was assessed using the area under the receiver operating characteristic curve (AUC). Results: Of the 284 eligible patients, 253 were included in the final analysis. Of these, 80 patients died in hospital, corresponding to an in-hospital mortality rate of 31.6%. LAR and CAR were significantly higher in non-survivors than in survivors at admission and at 24, 48, and 72 h after ROSC. After adjustment for potential confounders, LAR was associated with in-hospital mortality at all assessed time points. CAR was independently associated with in-hospital mortality at admission and at 48 and 72 h after ROSC, but not at 24 h. The AUCs of LAR for predicting in-hospital mortality ranged from 0.702 to 0.734, whereas those of CAR ranged from 0.640 to 0.690. Conclusions: In this single-center retrospective cohort of post-ROSC OHCA patients, sequential tracking of LAR and CAR profiles during the first 72 h after ROSC provided meaningful insights into in-hospital mortality. LAR showed a more consistent independent association with mortality and fair discriminatory performance, whereas CAR demonstrated limited prognostic value despite its association with mortality. Full article
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16 pages, 3085 KB  
Article
QRS-Corrected Prediction of the Diastolic Rest Period for Coronary CT Angiography in Patients with Complete Left Bundle Branch Block
by Tsubasa Morioka, Shingo Kato, Kouta Mitsutake, Hidenao Yanagisawa, Toshiharu Izumi, Tomokazu Sakano, Eiji Ishikawa, Hiroyuki Kamide and Daisuke Utsunomiya
J. Cardiovasc. Dev. Dis. 2026, 13(6), 285; https://doi.org/10.3390/jcdd13060285 (registering DOI) - 22 Jun 2026
Viewed by 121
Abstract
Background: Optimal phase selection in coronary computed tomography angiography (CCTA) is crucial. While the mid-diastolic slow-filling (SF) phase is typically predicted using a conventional formula based on heart rate and atrioventricular conduction time, its validity in complete left bundle branch block (CLBBB)—where pronounced [...] Read more.
Background: Optimal phase selection in coronary computed tomography angiography (CCTA) is crucial. While the mid-diastolic slow-filling (SF) phase is typically predicted using a conventional formula based on heart rate and atrioventricular conduction time, its validity in complete left bundle branch block (CLBBB)—where pronounced QRS prolongation induces severe mechanical dyssynchrony—remains unclear. We evaluated the impact of bundle branch block on cardiac-phase selection and validated a QRS-corrected predictive model. Methods: We retrospectively analyzed 94 patients (sinus rhythm, n = 40; complete right bundle branch block [CRBBB], n = 36; CLBBB, n = 18). Measured SF at the proximal right coronary artery was compared against predictions from the conventional formula (SF = −362 + 0.742 × [RR − PQ]) and a proposed QRS-corrected formula incorporating a “−(QRS − 100)” subtraction. To test the necessity of a novel model, regression analyses were reconstructed exclusively for the CLBBB cohort. Results: In CLBBB patients, the conventional formula critically overestimated SF by an average of 37.9 ms (RMSE 42.5 ms). Reconstructing simple and multivariate regression models exclusively for the CLBBB group yielded coefficients remarkably similar to the conventional formula, indicating that the fundamental physiological dependency on RR and PQ intervals remains intact despite the bundle branch block. Crucially, the simple proposed QRS-corrected formula successfully eliminated the overestimation bias (mean error −6.9 ms; p = 0.176) and demonstrated the highest predictive accuracy (RMSE 21.2 ms). Conclusions: A completely new predictive regression model is unnecessary for CLBBB patients. Simply incorporating a theoretical subtraction of pathological QRS prolongation optimally corrects the diastolic resting phase. Full article
(This article belongs to the Section Cardiovascular Clinical Research)
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16 pages, 2505 KB  
Article
Stroke Subtype as a Determinant of Mortality in Adult Patients on Extracorporeal Membrane Oxygenation
by Amir Mahdi Ghafarian, Ali Samani, Jawad Saad, Mohammad Ghafarian, Muaaz Wajahath, Sarah Foster, Seungwon Lim, Aliyah Sutton, Faddi G. Saleh Velez, Denise Battaglini and Andrea Loggini
J. Clin. Med. 2026, 15(12), 4790; https://doi.org/10.3390/jcm15124790 (registering DOI) - 20 Jun 2026
Viewed by 187
Abstract
Background: Stroke significantly increases morbidity and mortality in patients receiving extracorporeal membrane oxygenation (ECMO). This study evaluates the prognostic impact of stroke subtypes, acute ischemic stroke (AIS) and hemorrhagic stroke (HS), and neurologic injury severity in a contemporary adult population. Methods: We conducted [...] Read more.
Background: Stroke significantly increases morbidity and mortality in patients receiving extracorporeal membrane oxygenation (ECMO). This study evaluates the prognostic impact of stroke subtypes, acute ischemic stroke (AIS) and hemorrhagic stroke (HS), and neurologic injury severity in a contemporary adult population. Methods: We conducted a retrospective cohort study using the TriNetX federated electronic health record network, including adult patients who underwent ECMO between 1 October 2015 and 31 December 2025. Stroke was defined as a first-instance diagnosis of AIS, HS, or unspecified cerebrovascular event occurring within 24 h of ECMO cannulation during the index hospitalization. Propensity score matching (1:1 nearest neighbor) was performed to balance baseline demographics, comorbidities, anticoagulant use, and ECMO modality between the stroke and non-stroke cohorts. Primary outcomes included all-cause mortality at 30 days, 90 days, and 1 year. Secondary outcomes included cardiac arrest, seizures, palliative care utilization, and hospital readmission. Kaplan–Meier survival analysis and multivariable Cox proportional hazards modeling were performed. Results: Among 18,981 ECMO patients, 1481 (7.8%) developed a stroke within 24 h of ECMO cannulation, including 814 AIS (54.9%), 454 HS (30.6%), and 213 unspecified cerebrovascular events (14.4%). After propensity score matching, stroke was associated with significantly higher all-cause mortality at 30 days (RR 1.16), 90 days (RR 1.18), and 1 year (RR 1.18), all p < 0.05. Stroke was also associated with higher rates of cardiac arrest, seizures, hospital readmission, and palliative care utilization (all p < 0.001). AIS was associated with significantly lower mortality than HS at 30 days, 90 days, and 1 year (all p < 0.0001). In multivariable Cox regression, only HS was independently associated with increased 30-day mortality compared with no stroke. Markers of neurologic injury severity, including cerebral edema, brain compression, and coma, were among the strongest independent predictors of mortality. Conclusions: Stroke occurring early after ECMO cannulation is associated with substantially worse short- and long-term survival, with hemorrhagic subtype and markers of neurologic injury severity driving the strongest prognostic signals. These findings support early stroke recognition and subtype-informed prognostic discussions in ECMO patients. Full article
(This article belongs to the Special Issue Clinical Perspectives on Extracorporeal Membrane Oxygenation (ECMO))
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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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17 pages, 3049 KB  
Article
Optimizing Regional Access to Extracorporeal Cardiopulmonary Resuscitation: A Geographic-Information-System-Based Comparison of Hospital- and Prehospital-Initiated Strategies in Nara Prefecture, Japan
by Arisa Kinoshita, Hideki Asai, Yasuyuki Kawai, Keita Miyazaki, Koji Yamamoto, Hirozumi Okuda and Hidetada Fukushima
Healthcare 2026, 14(12), 1762; https://doi.org/10.3390/healthcare14121762 - 18 Jun 2026
Viewed by 117
Abstract
Background: Extracorporeal cardiopulmonary resuscitation (ECPR) can improve outcomes following refractory out-of-hospital cardiac arrest (OHCA); however, access is constrained by geography and resources. This study compared two strategies against the current system in Nara Prefecture, Japan: a two-stage hospital model using chest-pain network [...] Read more.
Background: Extracorporeal cardiopulmonary resuscitation (ECPR) can improve outcomes following refractory out-of-hospital cardiac arrest (OHCA); however, access is constrained by geography and resources. This study compared two strategies against the current system in Nara Prefecture, Japan: a two-stage hospital model using chest-pain network hospitals as ECPR-initiation sites, and a prehospital ECPR model using physician-staffed ambulances from two extracorporeal membrane oxygenation (ECMO)-ready hospitals. Methods: A geographic information system (GIS)-based simulation was conducted using emergency medical service (EMS) records of witnessed cardiac-origin OHCA cases (2017–2022). Isochrone analyses estimated areas reachable within a 60 min arrest-to-ECMO target. In the two-stage hospital model, patients located within a 15 min transport radius from chest-pain network hospitals were considered geographically covered. In the prehospital ECPR model, a physician-staffed ambulance was assumed to reach arrest sites within a 25 min travel-time radius from ECMO-ready hospitals. The study outcome was geographic coverage, defined as the proportion of cases within each service area; the two strategies were compared using McNemar’s test for paired proportions. Results: Among 1476 included cases, the coverage rate was as follows: current system, 28.7%; two-stage hospital model, 65.2%; prehospital model, 70.4% (p < 0.001). Certain eastern and southern mountainous regions remained outside both coverage areas. Conclusions: Using real-world EMS data, a mobility-focused prehospital ECPR strategy provided broader potential geographic access without requiring additional fixed hospital infrastructure than expanding hospital-based initiation sites. Optimization of prehospital deployment may represent a geographically feasible approach to expanding ECPR access in mixed urban–rural regions, though operational feasibility and cost-effectiveness require further evaluation. Full article
(This article belongs to the Section Healthcare Organizations, Systems, and Providers)
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2 pages, 180 KB  
Abstract
Exploration of Enantioselective Effects of MDPV on Zebrafish Embryogenesis
by Ariana Pérez-Pereira, Ondina Ribeiro, Luís Félix, Maria Tiritan, Cláudia Ribeiro and João Carrola
Proceedings 2026, 146(1), 71; https://doi.org/10.3390/proceedings2026146071 (registering DOI) - 18 Jun 2026
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Abstract
Introduction: Synthetic cathinones (SC) are an emerging class of neuroactive contaminants increasingly detected in aquatic systems due to their widespread recreational use. Their continuous release at ng–µg L−1 levels is particularly concerning, as these compounds are specifically designed to alter neural function, [...] Read more.
Introduction: Synthetic cathinones (SC) are an emerging class of neuroactive contaminants increasingly detected in aquatic systems due to their widespread recreational use. Their continuous release at ng–µg L−1 levels is particularly concerning, as these compounds are specifically designed to alter neural function, raising the likelihood of subtle yet ecologically relevant effects in non-target organisms. Among them, 3,4-methylenedioxypyrovalerone (MDPV) is one of the most-reported SC in wastewater and surface waters. Nevertheless, its chiral nature has been largely overlooked in ecotoxicological studies, despite growing evidence that enantiomers can differ markedly in biological activity, potentially leading to underestimated environmental risks. Objective: The ecotoxicological impact of racemic MDPV ((R,S)-MDPV) and its separate enantiomers ((R)-MDPV and (S)-MDPV) were examined using zebrafish (Danio rerio) as a model, focusing on survival and embryonic development. Methodology: Zebrafish embryos, at approximately 3-hours post-fertilization (hpf), were exposed over 96 h to environmentally relevant concentrations of MDPV forms (0.18−2.8 μg L−1). Each treatment and control group included 50 animals distributed across 5 replicates. Mortality was assessed at multiple developmental stages (7, 24, 48, 72, and 96 h), along with cumulative mortality. Developmental endpoints included spontaneous movements (24 h), heartbeat (48 h), and hatching rate (48 and 72 h), quantified using stereomicroscopy and video analysis. Results: MDPV showed concentration and enantioselective effects, with (S)-MDPV being the most toxic. Behavioral and cardiac responses varied across forms, while hatching depended on concentration and time without a clear enantioselective pattern. Conclusions: MDPV disrupts early zebrafish development, impairing survival and embryonic development in a concentration-dependent and enantioselective manner, with (S)-MDPV demonstrating greater toxicity. These findings emphasize the importance of considering chirality in the environmental risk assessment of psychoactive contaminants such as SC, as enantiomer-specific effects may influence organism fitness, survival, and broader ecological outcomes. Full article
(This article belongs to the Proceedings of The XI Iberian Congress of Ichthyology)
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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17 pages, 1761 KB  
Article
Development and Validation of a Machine Learning-Based Risk Assessment Tool for In-Hospital Mortality in Elderly Patients with Postoperative Hypoxemia Following Non-Cardiac Surgery
by Yuchen Zhou, Xinhe Zhou, Xiaozhu Liu, Chenghui Zhou and Yang Liu
J. Clin. Med. 2026, 15(12), 4725; https://doi.org/10.3390/jcm15124725 - 18 Jun 2026
Viewed by 163
Abstract
Background/Objectives: Postoperative hypoxemia is a frequent complication after non-cardiac surgery and is correlated with elevated mortality rates in elderly patients. However, a dedicated predictive tool for mortality in this specific patient subgroup remains unavailable. To construct and validate a machine learning (ML) model [...] Read more.
Background/Objectives: Postoperative hypoxemia is a frequent complication after non-cardiac surgery and is correlated with elevated mortality rates in elderly patients. However, a dedicated predictive tool for mortality in this specific patient subgroup remains unavailable. To construct and validate a machine learning (ML) model for predicting in-hospital mortality among elderly adults who develop hypoxemia after non-cardiac surgery. Methods: Data for this retrospective cohort study were obtained from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. The study encompassed patients aged 65 years or older who exhibited hypoxemia, defined as a PaO2/FiO2 ratio below 300 mmHg, within the initial 48 h of intensive care unit (ICU) stay. LASSO (Least Absolute Shrinkage and Selection Operator) regression was applied for feature selection, after which six distinct machine learning models and five conventional scoring systems were constructed and evaluated. SHapley Additive exPlanations (SHAP) was employed to improve model interpretability. Results: Out of 6051 eligible patients, 1838 (30.4%) succumbed during hospitalization. The XGBoost algorithm demonstrated superior predictive capability, achieving an area under the curve (AUC) of 0.794, along with a specificity of 0.917, accuracy of 0.769, and positive predictive value of 0.693. Critical predictors identified included administration of vasopressors, advanced age, and the PaO2/FiO2 ratio. Conclusions: The Extreme Gradient Boosting (XGBoost)-driven ML model provides accurate prediction of in-hospital mortality in elderly patients with postoperative hypoxemia after non-cardiac surgery, presenting a valuable instrument for early risk evaluation and potential intervention. Full article
(This article belongs to the Topic Machine Learning and Deep Learning in Medical Imaging)
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12 pages, 388 KB  
Article
Exercise Selection and Rest Interval Duration Differentially Affect Post-Exercise Cardiac Autonomic Responses Following Resistance Training
by Ryan Cysne Mire Corrêa, Jhonatan Martins de Souza, Giovane Coimbra Nascimento, Pedro Tuma Leonardo and Gustavo Vieira de Oliveira
J. Vasc. Dis. 2026, 5(3), 26; https://doi.org/10.3390/jvd5030026 - 18 Jun 2026
Viewed by 95
Abstract
Objectives: This study investigated the effects of exercise selection and rest interval duration on post-exercise cardiac autonomic modulation following resistance exercise (RE). Methods: Eleven (4 females) resistance-trained individuals performed a single RE session consisting of either a multi-joint exercise (back squat) [...] Read more.
Objectives: This study investigated the effects of exercise selection and rest interval duration on post-exercise cardiac autonomic modulation following resistance exercise (RE). Methods: Eleven (4 females) resistance-trained individuals performed a single RE session consisting of either a multi-joint exercise (back squat) or a single-joint exercise (leg extension), using rest intervals of 1 or 2 min between sets. Heart rate variability (HRV) was assessed at baseline (pre-exercise) and 30 min following the RE session. RR intervals were recorded for 15 min with participants resting in the supine position on an examination bed in a quiet environment. For HRV analysis, a 5-min artifact-free segment of RR intervals was selected and processed using Kubios HRV software, version 4.3.0 (Kubios Oy, Kuopio, Finland). The HRV metrics analyzed included the root mean square of successive differences (RMSSD), low-frequency normalized (LF), the low-frequency/high-frequency (LF/HF) ratio, and the standard deviation of transverse dispersion (SD1). Results: A significant main effect of time was observed for RMSSD, LF, and the LF/HF ratio. The back squat exercise elicited a significant reduction (p < 0.05) in vagal-related indices (RMSSD and SD1) regardless of interval duration. Longer rest intervals were associated with increased (p < 0.05) sympathetic modulation, as reflected by higher LF and LF/HF values 30 min post-exercise. No significant time × group interactions were observed for most HRV variables. Conclusions: Exercise selection and rest interval duration differentially influence post-exercise cardiac autonomic responses following RE. Multi-joint exercises induce greater vagal withdrawal, whereas longer rest intervals favor sympathetic predominance during recovery. These findings highlight the importance of manipulating RE variables to manage autonomic stress and recovery. Full article
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