Chronological age is a strong predictor of poor outcomes after ischemic stroke but may not fully capture underlying biological vulnerability. This study investigated whether age-related brain atrophy and plasma YKL-40, a marker of astroglial inflammation, mediate the association between age and the one-year risk of ischemic stroke recurrence or all-cause mortality. Data were obtained from 4,305 participants enrolled in the Third China National Stroke Registry. Baseline brain atrophy was quantified from structural T1-weighted MRI using an automated deep learning-based pipeline (FastSurfer), yielding hemispheric cortical and white matter volumes that were modeled as indicators of a latent atrophy construct. Structural equation modeling was applied to estimate direct and indirect pathways linking age, brain atrophy, YKL-40, and one-year composite outcomes, adjusting for sex, atrial fibrillation or flutter, hypertension, and diabetes, with indirect effects evaluated using 5,000 bootstrap resamples. The total effect of age on one-year outcomes was not significant (β = -0.011; 95% CI, - 0.060 to 0.038), whereas the total indirect effect was significant (β = 0.028; 95% CI, 0.005-0.050). Mediation was primarily attributable to YKL-40 (β = 0.026; 95% CI, 0.010-0.041), while the independent contribution of brain atrophy was minimal. The indirect effects accounted for approximately 255% of the total effect, indicating a suppressor-type mediation pattern in which direct and indirect effects operated in opposite directions. These findings suggest that advancing age confers increased long-term risk of stroke recurrence or death predominantly through astroglial inflammation rather than through a direct age effect, with brain atrophy modestly amplifying this risk, supporting the integration of neuroimaging and inflammatory biomarkers into translational stroke risk stratification.

A 58-year-old woman with recurrent paroxysmal atrial fibrillation and a history of cryoablation 3 years prior underwent an electrophysiological study for an irregular narrow complex tachyarrhythmia. The electrocardiogram showed positive P' waves in all leads except aVR, with the P' waves separated by large isoelectric intervals, indicating focal atrial tachycardia rather than atypical atrial flutter. High-resolution 3D mapping revealed a focal atrial tachycardia originating from the postero-septal part of the superior vena cava (in close proximity to the right superior pulmonary vein). Three applications at the superior vena cava level terminated the tachycardia and restored sinus rhythm. There were no recurrences. This case underscores the need for high-resolution electrophysiological mapping to identify the arrhythmia origin, especially in patients with prior procedures.

Tachycardia-induced cardiomyopathy (TIC) is most commonly associated with atrial fibrillation or atrial flutter, whereas atrioventricular nodal reentrant tachycardia (AVNRT) is rarely implicated because of its typically paroxysmal nature. We present the case of a 69-year-old man with a history of atrial fibrillation who presented with progressive dyspnea and persistent regular narrow-complex tachycardia initially interpreted as atypical atrial flutter with 2:1 atrioventricular conduction. Repeat electrical cardioversion was unsuccessful, and transthoracic echocardiography (TTE) demonstrated a newly reduced left ventricular ejection fraction (LVEF 20%) with global hypokinesis, while ischemic evaluation was negative. Due to refractory tachyarrhythmia and new non-ischemic cardiomyopathy, the patient underwent a comprehensive electrophysiology study with three-dimensional mapping, which revealed inducible typical AVNRT successfully treated with slow pathway modification. Pulmonary vein isolation and cavotricuspid isthmus ablation were additionally performed because of the patient's prior clinical history of atrial fibrillation and suspected atrial flutter. Following ablation, the patient experienced marked symptomatic improvement with recovery of LVEF to 50% at three-month follow-up, consistent with TIC. This case highlights the diagnostic limitations of surface electrocardiography in differentiating supraventricular tachycardias and demonstrates that AVNRT may rarely masquerade as atrial flutter and contribute to reversible cardiomyopathy, emphasizing the importance of an electrophysiology study in establishing a definitive diagnosis and guiding management.

Digoxin, a cardiac glycoside historically used for rate control in atrial arrhythmias and symptom relief in chronic heart failure, possesses a narrow therapeutic index and is highly susceptible to pharmacokinetic and pharmacodynamic disruption in critically ill patients. Its use in acute decompensated heart failure and cardiogenic shock is therefore controversial. We present the case of a 75-year-old woman with chronic heart failure with reduced ejection fraction who developed progressive bradycardia and cardiogenic shock after treatment with digoxin and amiodarone for 2:1 atrial flutter. Her hospital course was complicated by acute kidney injury, severe hyperkalemia, ischemic hepatitis, and persistent bradycardia following electrical cardioversion. Serum digoxin levels were supratherapeutic early in the intensive care unit course and subsequently normalized, though bradyarrhythmias persisted. The patient's presentation and clinical trajectory were consistent with BRASH (bradycardia, renal failure, AV-nodal blockade, shock, and hyperkalemia) syndrome , with amiodarone-digoxin interaction and systemic hypoperfusion likely amplifying myocardial digoxin sensitivity. She improved with supportive therapy, correction of metabolic derangements, withdrawal of AV-nodal-blocking agents, and cardioversion, without administration of digoxin-specific antibody fragments. This case highlights the importance of early recognition of BRASH physiology, cautious use of AV-nodal blockers in low-output states, and prioritization of underlying physiologic correction over reliance on serum drug levels alone in critically ill patients.

Targeted therapies have transformed the treatment landscape for patients with chronic lymphocytic leukemia (CLL). These therapies include the selective B-cell lymphoma-2 (BCL-2) inhibitor venetoclax and Bruton's tyrosine kinase (BTK) inhibitors (e.g., ibrutinib, acalabrutinib, zanubrutinib). Especially in a setting of long-term care, safety and tolerability are important considerations. Although generally well tolerated, targeted therapies for relapsed and refractory CLL are associated with potentially treatment-limiting untoward effects, often within weeks to months of initiating therapy. These include myelosuppression (e.g., neutropenia); tumor lysis syndrome, infection, and gastrointestinal effects with venetoclax; as well as cardiovascular diseases (e.g., hypertension, atrial fibrillation/flutter) and infection (e.g., pneumonia) with BTK inhibitors. Instrumental to management of these adverse effects are effective risk assessment, stratification, and modification; prophylaxis; and regimen modifications, with appropriate measures to minimize pharmacokinetic interactions.

Background: Atrial fibrillation (AF) and heart failure with preserved ejection fraction (HFpEF) usually coexist and are related to increased morbidity and mortality. Cardiovascular benefits have been demonstrated by drugs such as sodium-glucose cotransporter-2 inhibitors (SGLT2i) and GLP-1 receptor agonists including the dual GIP/GLP-1 receptor agonist tirzepatide (collectively, incretin-based therapies); however, their relative effectiveness in patients with concomitant AF and HFpEF remains undefined. Methods: We conducted a retrospective, propensity score-matched cohort study utilizing the TriNetX Global Collaborative Network. Adults with AF or atrial flutter with a diagnosis of HFpEF who initiated incretin-based therapies (GLP-1 receptor agonists or dual GLP-1/GIP receptor agonists) or SGLT2i were included; index medication was required to be initiated within 30 days of a qualifying AF/HFpEF diagnosis. 1:1 matching was performed based on baseline medications, demographics, and comorbidities. Co-primary outcomes were all-cause mortality, inpatient visits, and emergency department (ED) visits at 1 year. Secondary outcomes included myocardial infarction, ischemic stroke, acute kidney injury, transient ischemic attack, major adverse cardiovascular events (MACE; all-cause mortality/MI/stroke composite), and AF-related procedures. Agent-specific subgroup analyses were performed for semaglutide and tirzepatide separately. Sensitivity analyses were conducted at 6 months and 2 years. Results: 7624 patients were included in each cohort after matching (mean age: 70.8 years; 52% women). At 1 year, incretin-based therapy was associated with lower all-cause mortality (5.3% vs. 7.3%, HR 0.721, 95% CI 0.634-0.820; p < 0.001), fewer inpatient visits (30.0% vs. 37.4%, HR 0.743, 95% CI 0.702-0.787; p < 0.001), and no statistically significant difference in ED visits (27.0% vs. 28.0%; HR 0.946, 95% CI 0.888-1.007; p = 0.081) compared with SGLT2i. Incretin-based therapy was also associated with lower risk of MACE (HR 0.709), acute kidney injury (HR 0.751), myocardial infarction (HR 0.583), catheter ablation (HR 0.685), and electrical cardioversion (HR 0.472). No significant differences were observed in ischemic stroke or transient ischemic attack. These findings were broadly consistent at 6-month and 2-year follow-up, and directionally consistent in agent-specific subgroup analyses of semaglutide and tirzepatide. Conclusions: In this large propensity-matched cohort of patients with AF and HFpEF, initiation of incretin-based therapy (GLP-1 receptor agonists or dual GLP-1/GIP receptor agonists) was associated with lower all-cause mortality, fewer inpatient visits, and reduced cardiovascular events compared with SGLT2i. These findings, while subject to observational limitations, suggest potential benefits of incretin-based therapy in this high-risk population and support the need for prospective comparative trials.

Background: Metabolic reprogramming in critical illness and the physiological stress of general hospitalization represent fundamentally different states, yet it remains unknown if ketosis acts as a protective shield or a maladaptive metabolic response in the development of atrial fibrillation (AF) across these contexts. We examined urine and serum β-hydroxybutyrate measurements to understand the metabolic association among intensive care unit (ICU) and general hospital populations. Methods: This retrospective cohort study utilized the MIMIC-IV v3.1 database. Patients with preexisting AF or flutter were excluded. Ketosis was defined as urine ketone positivity (≥20 mg/dL) or serum β-hydroxybutyrate (≥1.0 mmol/L). The final analytic cohort included a general ward cohort (n = 13,641) and an ICU cohort (n = 10,251). Multivariable logistic regression, propensity score matching and subgroup analyses were performed. Results: In the ICU cohort, urine ketone positivity and elevated serum β-hydroxybutyrate were associated with lower incidence of AF (5.2% vs. 6.8%, p = 0.001; 3.1% vs. 9.4%, p = 0.034). After adjustment, urine ketone positivity remained independently associated with reduced odds of incident AF (adjusted OR 0.79, 95% CI 0.64-0.98, p = 0.032). Propensity-matched analyses demonstrated protective associations for urine ketones (OR 0.68, 95% CI 0.52-0.88, p = 0.004) and β-hydroxybutyrate (OR 0.24, 95% CI 0.08-0.70, p = 0.003). In contrast, urine ketone positivity in the general ward cohort was associated with higher incident AF (0.9% vs. 0.5%, p = 0.019) and increased adjusted odds (OR 2.62, 95% CI 1.03-6.66, p = 0.044). Urinary ketosis was associated with lower mortality and reduced inflammatory marker profiles across both the ICU and general ward cohorts. Subgroup analyses revealed directionally consistent ketone-AF associations across biological sex with no significant interaction effects. Conclusions: Endogenous ketones demonstrated a context-dependent association with incident AF across clinical acuity levels. These findings highlight ketone metabolism as a potential target for both arrhythmia monitoring and prevention.

Cardiovascular diseases (CVDs) are a leading cause of morbidity and mortality, and physical activity (PA) is central to secondary prevention. However, factors associated with PA among individuals with CVDs remain poorly understood, with few studies using accelerometer-based methods. This cross-sectional study examined the associations between accelerometer-measured PA and demographic, socioeconomic, lifestyle factors, and comorbidity in a large Swedish cohort of individuals with CVDs. Participants aged between 50 and 64 years with a confirmed diagnosis of angina pectoris, myocardial infarction, atrial fibrillation and flutter, heart failure, or stroke were included. Moderate-to-vigorous physical activity was measured using hip-worn triaxial accelerometers over seven consecutive days and categorized into tertiles of low, medium and high PA level. Demographic, socioeconomic, lifestyle factors, and comorbidities were assessed through questionnaires and registry data. Associations with PA levels were analyzed using multiple ordinal logistic regression. A total of 1,484 participants (32% women; median age 60.2 years) were included. Being in the oldest age group was significantly associated with lower odds of having a higher PA level (OR = 0.59; 95% CI [0.44, 0.77]), as well as female sex (OR = 0.73; 95% CI [0.59, 0.91]), regular/occasional smoking (OR = 0.37; 95% CI [0.26, 0.52]), and having one (OR = 0.61; 95% CI [0.48, 0.77]) or more comorbidities (OR = 0.45; 95% CI [0.30, 0.68]). A healthy diet was significantly associated with higher PA levels (OR = 1.84; 95% CI [1.46, 2.31]). Financial strain, level of education and alcohol consumption had no association with PA. Using data from a representative sample of middle-aged adults, the findings indicate that engagement in PA is primarily associated with lifestyle factors, demographic characteristics, and comorbidity. These identified characteristics may inform future research aimed at CVD populations with low PA. Further research should investigate mediating and moderating pathways to clarify how these factors influence PA.

The management of paroxysmal atrial fibrillation with conversion pauses remains challenging, with catheter ablation and permanent pacemaker implantation representing the main therapeutic strategies. Catheter ablation may eliminate atrial fibrillation paroxysms and prevent conversion pauses, whereas pacemaker implantation combined with antiarrhythmic therapy for rhythm control is another accepted option. We report a case of successful management of paroxysmal atrial fibrillation with conversion pauses using antiarrhythmic agents for rhythm control prior to catheter ablation. A 61-year-old woman had episodes of palpitations, dizziness, and presyncope. Ambulatory 12-lead 24-hour ECG monitoring showed 51 episodes of atrial fibrillation and atrial flutter with conversion pauses after each of them; the longest pause was 7460 ms. Atrial fibrillation lasted for 46.9% of the total monitoring time. When ambulatory 24-hour monitoring was performed, the patient was highly symptomatic (complaints of palpitations and fear of death were predominant, but dizziness episodes were also noted). Catheter ablation was unavailable in the short-term period and permanent pacemaker implantation was not accepted by the patient. Thus, flecainide at a dose of 100 mg BID under close supervision for rhythm control was administered. Also, anticoagulation with edoxaban was provided. The patient remained asymptomatic until ablation was performed. Pulmonary vein isolation with pulsed field ablation and cavotricuspid isthmus ablation was performed 10 days after ambulatory ECG monitoring. There were no paroxysms of atrial fibrillation after ablation. Antiarrhythmic agents in patients with conversion pauses may worsen sinus node function but may also eliminate atrial fibrillation paroxysms preventing conversion pauses. Thus, catheter ablation may be an option for a patient presenting with atrial fibrillation and conversion pauses to avoid unnecessary permanent pacemaker implantation. Short-term pharmacological bridging with flecainide under close supervision may be used in patients with atrial fibrillation and conversion pauses without other signs of sinus node dysfunction, providing effective rhythm control.