Ischemic heart disease is a leading cause of global morbidity and mortality, yet early diagnosis and targeted therapies remain limited. Exosomes, small extracellular vesicles carrying nucleic acids, proteins, and lipids, mediate intercellular communication and show promise for diagnostic and therapeutic use due to their stability, biocompatibility, and targeted delivery. Circulating exosomal profiles reflect myocardial pathology, enabling early detection, risk stratification, and monitoring. Exosomes from mesenchymal stem cells, immune cells, endothelial cells, and other stem cells exert cardioprotective effects. This review summarizes advances in exosome-based diagnostics and therapies and highlights their potential as biomarkers and innovative treatments.

Acute coronary syndrome, driven by vulnerable plaque (VP) instability, is a major cause of cardiovascular mortality. Current diagnostic methods for VPs are limited by invasiveness or low specificity, highlighting the need for non-invasive biomarkers. Using single-cell RNA sequencing (scRNA-seq) of peripheral blood mononuclear cells (PBMCs) from coronary artery disease (CAD) patients with VPs and controls, we identified circulating T cell-platelet aggregates (TPAs) significantly enriched in VP patients and linked to plaque instability via pro-inflammatory pathways. Through high dimensional weighted gene co-expression network analysis, we discovered TPAs' hub genes and demonstrated their role in plaque destabilization. Furthermore, employing machine learning, including Boruta, least absolute shrinkage and selection operator (LASSO) regression and support vector machine-recursive feature elimination (SVM-RFE), we screened for five blood biomarkers that can serve as diagnostic indicators for VPs. Our study demonstrates that TPAs are critically involved in VPs formation. Furthermore, we identified EPHB6, STAT1, RPL23, IKZF3 and AHCY as potential circulating biomarkers for non-invasive detection of VPs.

Tricuspid regurgitation (TR) is a highly morbid and often untreated valvular heart disease. New devices are under development to address this unmet need, necessitating valid models to test their efficacy. Aim of this study was to assess feasibility and reliability of pulmonary artery banding (PAB) as a pathological acute model of functional TR. Eight pigs underwent right thoracotomy, with an umbilical tape placed around the main pulmonary trunk, followed by controlled reduction of the pulmonary artery lumen via a tourniquet system. No animals died during the procedure. After PAB, right ventricular (RV) mean pressure, RV basal and mid-diameter and tricuspid septo-lateral diameter significantly increased (+ 97%, + 23%, + 32%, + 20%, p < 0.01 for all). Consequently, TR was at least moderate-to-severe in all the animals and these modifications remained stable for up to one hour. PAB therefore represents a reliable, one-step model of functional TR ideal to test the efficacy of new tricuspid devices.

Coronary obstruction following transcatheter aortic valve-in-valve implantation (VIV-TAVI) carries a high mortality risk. This in-vitro study assessed coronary perfusion in a high-risk VIV-TAVI scenario. A patient deemed at high-risk and treated with preventive Chimney stenting was selected as case study. A 3D-printed aortic root model was fabricated from pre-operative imaging and used to replicate the patient's VIV-TAVI setting. A CoreValve-Evolut-23 was implanted within a Trifecta-19 at five depths, with commissural alignment and 60° misalignment, to explore procedural variability and associated risk margins. The model was tested in a pulsatile mock loop with a coronary perfusion simulator. Flow and pressure were recorded pre- and post-VIV-TAVI under physiological conditions. Across all tested configurations, VIV-TAVI didn't significantly impair left or right coronary flows. The recommended depth optimized hemodynamic valve performance. Findings suggest refining coronary obstruction risk stratification in VIV-TAVI to improve decision-making regarding preventive interventions.

Social interaction supports brain health and recovery after neurological injury. Yet no validated tool exists for real-time measurement in individuals with and without neurological deficits. We developed SocialBit, a lightweight, privacy-preserving machine learning algorithm that detects social interactions using ambient audio features on a commercial smartwatch. In a prospective validation study, we evaluated SocialBit against livestream minute-by-minute human-coded ground truth in 153 hospitalized stroke patients who wore the device for up to 8 days, generating 88,918 min of observation. In these patients, the stroke severity and cognition spanned broad clinical ranges (NIH Stroke Scale 0-25; Montreal Cognitive Assessment 8-30), and 24 patients had aphasia across diverse subtypes, including severe presentations. SocialBit achieved high overall performance (sensitivity 0.87, specificity 0.88, area under the curve 0.94) and maintained accuracy in patients with language deficits (AUC 0.93). Despite lower temporal sampling, SocialBit produced interaction frequency distributions closely matching minute-by-minute human coding. Performance was robust across environments and interaction types. Of clinical relevance, SocialBit showed that patients with more severe strokes engaged in less social interaction, paralleling human-coded results. SocialBit is an accurate digital biomarker of social interaction with potential applications in remote monitoring and clinical trials.

Primary aldosteronism (PA) is the most common cause of secondary hypertension and is increasingly recognized as a spectrum disorder, ranging from subclinical to overt forms. Clinical manifestations include hypertension, often resistant, and may be accompanied by hypokalemia. Beyond BP elevation, PA is associated with a disproportionately high risk of cardiovascular and metabolic complications compared to essential hypertension, including coronary artery disease, arrhythmias, heart failure, left ventricular hypertrophy, stroke, metabolic syndrome and impaired glucose metabolism. The negative effects of aldosterone excess induce greater target organ damage than seen in primary hypertension, including arterial stiffness, cardiac remodeling, and renal dysfunction. Targeted treatments such as mineralocorticoid receptor (MR) antagonists and adrenalectomy have demonstrated efficacy in reducing these risks and improving patient outcomes. Therefore, early detection and management of PA are essential for preventing long-term cardiovascular and metabolic complications.

Guidelines permit up to 360 J for synchronised biphasic electrical cardioversion (ECV) in atrial fibrillation (AF) lasting >48 hours. The CHESS randomised trial reported higher first-shock success with fixed 360 J versus a low-escalation 125-150-200 J sequence. Much of this evidence used adhesive pads without manual pressure and anterior-posterior positioning. We evaluated a 200 J-first, fixed-escalation biphasic ECV protocol delivered with a standardised technique in an emergency department (ED).

Single-centre retrospective observational study of consecutive adults undergoing elective ECV for symptomatic AF >48 hours (2019-2021). Procedures used hand-held paddles with firm chest pressure in the anterolateral (AL) position under deep sedation. The predefined sequence was 200→300→360 J if needed. The primary outcome was restoration of sinus rhythm (SR) documented on a 12-lead ECG within 120 min. Secondary outcomes were first shock success at 200 J, cumulative efficacy, SR to discharge without post-ECV antiarrhythmics, adverse events and subgroup efficacy. Results were contrasted descriptively with 360 J-first cohorts (CHESS).

Of 451 ECV procedures identified, 374 were eligible. The primary outcome was achieved in 97.3% (364/374; 95% CI 95.5 to 98.7). First-shock success with 200 J was 88.0% (329/374; 95% CI 84.3 to 90.9). Escalation to 300 J and 360 J was required in 44 and 15 patients. SR was maintained to discharge in converted patients. Two minor adverse events occurred (2/374, 0.5%) and no serious adverse events were recorded.

A 200 J-first, fixed-escalation biphasic protocol with a standardised technique (manual paddles, firm pressure, AL placement) achieved high first-shock and excellent cumulative efficacy for AF>48 hours in real-world ED care without routine pharmacologic adjuncts. Findings support considering a 200 J-first approach and motivate pragmatic multicentre randomised controlled trials directly comparing 200 J-first versus 360 J-first under harmonised technique with objective safety endpoints.

Persistent atrial fibrillation (AF) remains challenging to treat with catheter ablation. The left atrial posterior wall (PW) may represent an important non-pulmonary vein (PV) substrate; however, randomised trials have not demonstrated improved outcomes with adjunctive PW isolation (PWI), potentially reflecting technical limitations of thermal ablation rather than a lack of mechanistic relevance. Pulsed-field ablation (PFA) is a non-thermal ablation modality that selectively targets myocardial tissue and may enable safer and more consistent PWI. We compared real-world outcomes of PFA and radiofrequency ablation (RFA) for combined PV isolation and PWI in patients with persistent AF.

200 consecutive patients (100 PFA and 100 RFA) undergoing combined PVI and PWI were retrospectively followed for up to 12 months. Baseline characteristics were broadly similar; however, PFA patients had lower left ventricular ejection fraction (LVEF) (43.5% (35.5-55.5%) vs 47% (40-58), p=0.01) and higher CHA₂DS₂-VA risk score (3 (2-4) vs 2 (1-3), p=0.01). Primary outcomes were acute procedural success and freedom from recurrent atrial tachyarrhythmia (AT) at 6 and 12 months.

PFA achieved near-universal PWI compared with RFA (99% vs RFA: 65%, p<0.005), with shorter procedure duration (106 vs 143.5 min, p<0.005), reduced left atrial dwell time (62 vs 98 min, p<0.005), and faster time to PVI and PWI (all p<0.005). Major non-vascular complications were uncommon (1.5%) and similar between groups. At 12 months, freedom from recurrent AT was higher with PFA (70% vs RFA 54%, p=0.03), with lower odds of first detected AT recurrence in adjusted time-to-event analysis (OR 0.46 (0.26-0.82), p=0.009).

In this real-world cohort, PFA was associated with a higher rate of acute PWI and greater freedom from AT compared with RFA, without a signal of increased complications. Prospective randomised studies are needed to define the role of PWI delivered with PFA in patients with persistent AF, including those with reduced LVEF.

Stroke is a prevalent neurological condition that frequently results in long-term disabilities and considerable societal costs. While existing rehabilitation approaches provide some benefits, residual motor impairments often persist and become permanent, leading to ongoing activity restrictions. Music-based intervention, such as the Ronnie Gardiner Method (RGM), adheres to best practice principles of stroke rehabilitation by simultaneously engaging motor, sensory, cognitive and emotional functions, potentially offering enhanced recovery outcomes. However, research examining its effectiveness in chronic stroke rehabilitation remains limited.

This multicentre, randomised controlled trial will recruit 84 community-dwelling individuals with chronic stroke over a 2-year period across four sites in Sweden. Participants will be randomly assigned to either an intervention group receiving RGM training (n=42) or a passive waitlist control group (n=42). Only the investigators and outcome assessors will remain blinded to group allocation. RGM training consists of 60 min group sessions twice weekly for 12 consecutive weeks. The primary outcome is to evaluate the effectiveness of RGM training on balance performance using the Mini-Balance Evaluation Systems Test. Secondary outcomes include assessment of gait function (10-Metre Walk Test, 6 min Walk Test, Short Physical Performance Battery), upper limb function (9-Hole Peg Test, Observational Drinking Task Assessment), cognitive abilities (Victoria Stroop Test, Rey Complex Figure Test, Memory Test), fear of falling (Falls Efficacy Scale-International) and stroke-related functional impact (Stroke Impact Scale-16). Broader health-related quality of life will be assessed using the RAND 36-Item Health Survey, EuroQol 5-Dimension 5-Level, and depressive symptoms will be measured with the Montgomery-Åsberg Depression Rating Scale. All outcomes will be assessed at baseline, postintervention and at a 3-month follow-up. Additional assessments will include qualitative evaluations of participants' and trainers' subjective experiences, cognitive screening (Montreal Cognitive Assessment) and postintervention enjoyment assessment (Physical Activity Enjoyment Scale).

Ethical approvals for the study have been obtained from the Swedish Ethical Review Authority (Dnr: 2025-01269-01 and Dnr: 2025-08232-02). The results will be disseminated via peer-reviewed journal publications, conference presentations and targeted communication with stakeholders and the media.

NCT06979050.

Total-body PET systems with long axial field of view (LAFOV) are now commercially available and represent the state of the art in PET imaging. These systems provide wide anatomical coverage and markedly increased detection sensitivity. Clinical studies have demonstrated enhanced image quality, superior quantification, and benefits for tracer kinetic modeling through dynamic imaging. LAFOV PET/CT allows for substantial reductions in acquisition time and radiation dose while maintaining diagnostic image quality. Full-body coverage enables dynamic whole-body imaging, which enables tracer kinetic modeling across multiple organs and the large vascular structures, offering new opportunities for studying their interactions in cardiovascular and systemic diseases. Furthermore, these systems facilitate the development of new PET methods, including pharmacokinetics of new tracers. This review discusses the emerging opportunities and challenges associated with the application of LAFOV PET/CT systems in cardiovascular diseases.