Although physical activity (PA) participation has known health benefits, many individuals with hypermobility spectrum disorders (HSD) and hypermobile Ehlers-Danlos syndrome (hEDS) have difficulties participating in PA. HSD/hEDS affect approximately 1 in 500 people and are more prevalent in females. HSD/hEDS may result in frequent joint injuries, chronic pain, and generalized fatigue. These symptoms, and a fear of new or reinjury, may result in barriers to PA participation. Overall, there is limited research on PA in this population. Previous exercise reviews have not included structured PA such as sports and occupational activities; unstructured PA such as play, household, or leisure activities; or younger ages, including children. Additionally, some females with HSD/hEDS report experiencing more frequent joint injuries and worsening pain and fatigue during times of hormonal transitions, such as puberty, pregnancy, as well as cyclically across the menstrual cycle. Some females also report improvements in symptoms and a reduction in injury frequency following menopause. The impacts of PA during these times of changing hormone levels for females living with HSD/hEDS are uncertain. A clear understanding of what types of structured and unstructured PA are safe and helpful for individuals of all ages with HSD/hEDS, and if PA should be adapted during times of female hormonal changes, is lacking.

We propose a scoping review protocol to map and synthesize the evidence regarding considerations that may impact structured and unstructured PA participation in HSD/hEDS for individuals of all ages and during times of female hormonal transitions.

A scoping review will be conducted using Covidence (Veritas Health Innovation Ltd) and Microsoft Excel (Microsoft Corp) to map the evidence regarding the impacts of PA on safety, physical health, and quality of life. These outcomes will be assessed using the World Health Organization International Classification of Functioning, Disability and Health framework.

The database search was performed on August 22, 2024, and updated on September 8, 2025. Data extraction started in September 2025 and is ongoing. The results are expected to be published by August 2026.

This proposed scoping review will aid in defining critical research directions regarding PA in HSD/hEDS, which may help inform guidelines outlining the risks and benefits of structured and unstructured PA. This review will also help define existing evidence for age-specific and hormone-related considerations regarding the impacts of PA in this population. This is particularly important as PA may help ameliorate the physical and mental symptoms associated with HSD/hEDS and may improve quality of life for these individuals across the lifespan.

Persistent atrial fibrillation (AFib) is the most common chronic arrhythmia in adults in the United States and is associated with significant morbidity, including thromboembolic events, stroke, and heart failure. Despite available therapies such as catheter ablation and antiarrhythmic drugs, AFib remains incurable for many patients. Our study aims to develop a large-animal model of AFib in Yucatan miniswine to support investigation of new therapeutic approaches for this disease.

Yucatan miniswine were selected for their physiological similarity to humans and suitable size for long-term studies. Each animal was initially fitted with an external FitBark 2.0 collar to track activity as a surrogate for quality of life. Animals then underwent implantation of an atrial pacing lead in the right atrial appendage, a pacing generator, and an insertable cardiac monitor (ICM Reveal LINQ™) implanted subcutaneously along the left scapula. One week after the pacemaker implantation, animals underwent rapid atrial pacing to induce persistent AFib. All procedures were performed in accordance with relevant institutional and regulatory guidelines.

Atrial fibrillation was successfully induced in 4 of 6 animals within 80.3 ± 22.3 days of initiating pacing with three animals going into persistent AFib and one animal going into paroxysmal AFib. The definition of persistent AFib was that animals remained in AFib for more than 14 days after pacing was discontinued. Paroxysmal AFib was defined as AFib lasting less than 14 days. Activity levels decreased following persistent AFib onset, indicating a decline in overall health and quality of life. Histopathological analyses showed significant increases in fibrosis and loss of atrial cardiomyocytes after persistent AFib was induced in swine. Several anatomical and technical challenges, particularly related to vascular access and cardiac dimensions, were overcome through customized surgical strategies, including jugular venous cut-downs, lateral cervical ICM implantation, long vascular sheaths, custom styluses, and perioperative antibiotic coverage. These innovations were critical to establishing a robust and reproducible persistent AFib model.

Guideline-Directed Medical Therapy (GDMT) is central to managing ischemic heart disease (IHD), yet its implementation remains suboptimal in low- and middle-income countries (LMICs), including Pakistan.

This study assessed the knowledge, attitudes, and practices (KAP) of healthcare professionals (HCPs) toward GDMT and identified key barriers to its application.

A cross-sectional survey was conducted among HCPs including cardiologists and clinical pharmacists using a validated questionnaire. Data was collected from Punjab Institute of Cardiology, Lahore, Pakistan using convenience sampling. Descriptive statistics, t-tests, ANOVA, Mann-Whitney U, Kruskal-Wallis, and multiple linear regression analyses were used to evaluate KAP scores and their association with demographic and professional role. Statistical adjustment for multiple comparisons was done by Bonferroni correction.

A total of 76 HCPs participated in the survey, comprising 42 cardiologists (55.3%) and 34 clinical pharmacists (44.7%). he overall mean knowledge score was 18.64 ± 2.02 out of 22 (84.7%). However, cardiologists (M = 19.54) scored significantly higher than clinical pharmacists (M = 17.52, p < 0.001); thus rejecting the null hypothesis. Knowledge scores were significantly higher among older professionals, those with postgraduate education, and clinic-based practitioners (p < 0.05). The average attitude score was 10.42 ± 2.06 out of 14 (74.4%), with younger professionals (aged 28-33), cardiologists, and postgraduates showing more favorable attitudes (p < 0.05). The mean practice score was 9.51 ± 2.55 (67.9%), with no significant differences by gender, role, or setting. Regression models showed age and profession significantly predicted knowledge, while attitude was influenced by education, experience, gender, and profession. Practice behaviors were not predicted by any demographic variables. Key barriers to GDMT implementation included limited consultation time (47.4%) and poor patient adherence (25%).

Although GDMT knowledge and attitudes were generally high among Pakistani cardiologists and clinical pharmacists, reported practice remained moderate. The results underscore the need for targeted educational interventions and system-level strategies to support consistent GDMT implementation.

Initial clinical and imaging associations in Takayasu's arteritis (TAK) are poorly defined.

To characterize initial manifestations, their associations, and long-term outcomes in a TAK cohort.

A single-center retrospective cohort study (2000 to 2024) included patients diagnosed with TAK. The significance level was set at p<0.05.

Among 203 patients identified, 54 were excluded due to incomplete data. The final cohort comprised 149 patients (89.9% female), with a median age at diagnosis of 31 years. At diagnosis, 92.6% were symptomatic. Claudication of upper (36.2%) and lower (30.9%) limbs was frequent, alongside advanced vascular damage like stenosis (85.9%) and occlusions (52.3%). Upper limb claudication was independently predicted by reduced upper limb pulses (OR=4.83; 95%CI=2.08-11.24; p=0.001) and right subclavian artery occlusion (OR=8.06; 95%CI=1.94-33.44; p=0.004). Lower limb claudication was predicted by right subclavian artery occlusion (OR=6.65; 95%CI=2.05-21.61; p=0.002), right subclavian artery thickening (OR=5.12; 95%CI=1.18-22.71; p=0.029), and left subclavian artery stenosis (OR=2.71; 95%CI=1.21-60.56; p=0.016). Over a median 10-year follow-up, despite 91.3% remission, cardiovascular comorbidities increased, and 26.8% required surgery.

Limb claudication is a key prognostic indicator of advanced radiological damage and diagnostic delay. This is reinforced by a long-term dissociation between high clinical remission and progressive vascular disease, demanding vigilant monitoring.

Evidence on the safety and anti-ischemic effects of exercise-based cardiac rehabilitation (ECR) in patients with refractory angina (RA) remains limited.

To evaluate the safety and efficacy of a 12-week ECR program in patients with RA, focusing on improvements in symptoms, functional capacity, and ischemic burden assessed by exercise stress echocardiography (ESE).

This was a prospective, single-center, randomized controlled trial evaluating a 12-week ECR program in patients with RA. Forty-five patients were randomized to either the rehabilitation group (RG), receiving ECR, or the control group (CG), receiving medical treatment (MT) alone. Outcomes included mortality, cardiovascular events, anginal symptoms, and parameters from ESE and cardiopulmonary exercise testing (CPET). Statistical significance was set at p < 0.05.

In ESE, exercise duration was significantly greater in RGpost (after ECR) compared to RGpre (before ECR) (∆ = 63.24 ± 19.87 s; p < 0.01). Angina quantification was lower in RGpost than in RGpre, CGpost (after MT alone), and CGpre (before MT alone) (∆ = -1.64 ± 0.48 n, p < 0.01; -3.10 ± 0.97 n, p < 0.01; and -2.73 ± 0.92 n, p = 0.01, respectively). The angina threshold was higher in RGpost than in RGpre and CGpost (∆ = 89.66 ± 33.16 s, p = 0.04; and 111.76 ± 42.25 s, p = 0.04, respectively). Improvement in ischemic burden on ESE was demonstrated by increased time to ischemic threshold in RGpost compared to RGpre, CGpost, and CGpre (∆ = 83.23 ± 21.84 s, p < 0.01; 98.44 ± 35.11 s, p = 0.03; and 109.34 ± 34.00 s, p < 0.01, respectively). In CPET, RGpost showed increased exercise duration (∆ = 104.54 ± 28.09 s, p < 0.01) and distance covered (∆ = 131.23 ± 30.48 m, p < 0.01) compared to RGpre. No significant differences in VO2 were observed between groups. Two patients in the CG group died. One patient in the RG group experienced prolonged angina during training. No significant differences in major cardiovascular events were observed between groups.

The 12-week ECR-program was safe and effective in improving exercise duration, distance covered and ischemic burden on ESE in patients with RA.

Advanced heart failure (HF) is associated with high morbidity and mortality rates, compromising the functionality and quality of life of patients and their families. Hospitalizations exacerbate disease severity, particularly when inotropic therapy is required. Palliative care (PC) supports the management of suffering caused by severe illnesses but is infrequently utilized in cardiology.

To evaluate the integration of PC in the management of decompensated HF, identifying opportunities to enhance patient care.

This unicentric, retrospective, observational study was conducted between February 2015 and May 2018 with HF patients undergoing inotropic therapy. The study analyzed referrals for PC, the approach adopted by the PC-consultation team, and patient outcomes, including an analysis of 5-year survival rates. Statistical significance level: 5%.

A total of 492 patients were included (66.9% male, median age 63 years, IQR 52-72). PC referral occurred in 23% of cases, with a median of 8.0 days (IQR 4.0-20) before death. Only 14% of intensive care patients were referred, and no transplant patients received PC evaluations. Patients assessed by the PC team were more involved in decision-making and received more opioid prescriptions for symptom management than those managed exclusively by cardiologists (p<0.01). In-hospital and 5-year mortality rates were 42% and 80%, respectively.

Patients experiencing decompensated HF demonstrate high mortality rates and are rarely referred to PC, often in the final days of life, limiting the potential benefits of this approach. Enhanced medical education in PC and the development of strategies to promote its integration may improve patient outcomes.

Pulmonary valve regurgitation (PR) is often encountered in cardiac conditions, including heart failure (HF). Although typically tolerated, severe PR can lead to right ventricular dysfunction and negative clinical outcomes; however, its specific impact within the wider HF population needs further clarification.

This study was designed to evaluate the association between the severity of PR and N-terminal pro-B-type natriuretic peptide (pro-BNP) levels, its effect on functional capacity measured by the six-minute walk test (6MWT), and the incidence of significant clinical problems in patients with HF.

Between 2016 and 2023, we conducted a retrospective study involving 579 HF patients who underwent echocardiography at two tertiary institutions. Based on semi-quantitatively evaluated PR severity, patients were classified into four groups: No PR, Mild PR, Moderate PR, and Severe PR. Group comparisons used Chi-square tests and Kruskal-Wallis. Multivariate linear regression and Spearman correlation analyses were performed to assess associations.

Pro-BNP levels significantly increased across PR severity groups (Median: 2,157 pg/mL [No PR] to 23,541 pg/mL [Severe PR], p<0.0001). In contrast, 6MWT distance significantly decreased with deteriorating PR severity (Median: 254 m [No PR] to 72 m [Severe PR], p<0.0001). The prevalence of orthopnea and pleural effusion also increased with PR severity. After multivariate adjustment, PR severity remained independently associated with higher pro-BNP levels (β=0.48, p=0.002) and lower 6MWT distance (β=-0.39, p=0.008).

In patients with HF, increasing severity of PR is independently associated with elevated pro-BNP levels, reduced functional capacity, and a higher burden of clinical complications.

This study evaluated prevalence, incidence, and progression of carotid intima-media thickness (cIMT) and carotid artery plaques (CAP) in rheumatoid arthritis (RA) patients compared with controls during 8 years of follow-up. A case-cohort analysis of data from the ELSA-Brasil cohort was conducted, with cIMT and CAP measured by carotid ultrasound at baseline and follow-up. Linear regression was used to estimate cIMT mean and progression (ΔcIMT). Logistic regression was used to estimate odds ratios (OR) for elevated cIMT (≥75th percentile), CAP prevalence, incidence, and progression. Models were adjusted for sociodemographic and cardiovascular risk factors, excluding participants with prior cardiovascular disease. A total of 1,289 participants (188 RA, 1,101 controls) were included in the cIMT analysis and 585 (93 RA, 492 controls) in the CAP analysis. RA was not associated with baseline cIMT (β=0.00; 95%CI: -0.02-0.02; P=0.930), high cIMT (OR=1.04; 95%CI: 0.69-1.57; P=0.864), or ΔcIMT (β=0.00; 95%CI: -0.01-0.02; P=0.688). Incidence of elevated cIMT showed a non-significant trend toward higher risk in RA (OR=2.01; 95%CI: 0.88-4.59; P=0.098). No associations were found for CAP prevalence at baseline (OR=1.64; 95%CI: 0.92-2.91; P=0.090), prevalence at follow-up (OR=0.75; 95%CI: 0.41-1.36; P=0.342), incidence (OR=0.78; 95%CI: 0.37-1.63; P=0.508), or progression (β=-0.33; 95%CI: -0.72-0.07; P=0.102). This study found no independent association between RA and cIMT or CAP.

The aim of this study was to examine the effects of tDCS during intensive word-finding therapy on subacute aphasia after stroke. A single-case study with an 86-year-old man with four years of formal education, diagnosed with an ischemic stroke in the left hemisphere, resulting in non-fluent aphasia of the mixed type, accompanied by acquired apraxia of speech. For this purpose, the Montreal-Toulouse Language Assessment Battery - Brief Version was administered at five different time points: (A1) one week before the start of treatment; (A2) after the first session; (A3) after five sessions; (A4) after ten sessions and; (A5) after 30 days without intervention. The Naming and Visual Recognition Test was also administered at points A1, A4 and A5. After the intervention, improvements were noted in word naming and verbal word comprehension. There was a reduction in linguistic errors such as paraphasias. These results support the combination of tDCS and behavioral training.

Variants of uncertain significance (VUS) in genes implicated in thoracic aortic aneurysm (TAA) present clinical challenges due to ambiguous pathogenicity and low patient representation. This study investigates the pathogenic potential of missense VUS in the ROBO4 gene, previously associated with vascular integrity and ascending aortic aneurysm. Clinical and genetic data from five patients with heterozygous ROBO4 VUS and thoracic aortic aneurysms or dissections were analyzed. Computational tools including AlphaFold2, AlphaMissense, REVEL, PolyPhen-2, SIFT, FATHMM, MutationTaster2, GranthamMatrix, and PhastCons were utilized to predict pathogenicity and structural impacts. Patients exhibited varying severities of aortic pathology, from elective aneurysm repairs to extensive familial aneurysmal histories. Structural modeling revealed significant differences in residue positions and biochemical properties, particularly for extracellular domain variants affecting critical beta-sheet structures involved in vascular stability. Notably, patient-specific predictions aligned computational evidence with clinical severity, suggesting potential genotype-phenotype correlations. For example, a variant (Q44P) showed strong pathogenic predictions coinciding with severe familial presentations. These computational predictions, validated by clinical data, highlight a novel and efficient workflow for evaluating VUS pathogenicity, informing precision medicine, and guiding counseling for aortic degenerative diseases. Ultimately, we demonstrate the value of integrating computational modeling with clinical data to decipher the pathogenic significance of genetic variants in cardiovascular diseases.