Atrial cardiomyopathy and remodeling play pivotal roles in the development of atrial fibrillation (AF) and heart failure (HF), involving complex changes in atrial structure and function. These changes facilitate the progression of AF and HF by creating a dynamic interplay between mechanical stress and electrical disturbances in the heart. Sodium–glucose cotransporter 2 inhibitors (SGLT2is), initially developed for the management of type 2 diabetes, have demonstrated promising cardiovascular benefits, being currently one of the cornerstone treatments in HF management. Despite recent data from randomized clinical trials indicating that SGLT2is may significantly influence atrial remodeling, their overall effectiveness in this context is still under debate. Given the emerging evidence, this review examines the molecular mechanisms through which SGLT2is exert their effects on atrial remodeling, aiming to clarify their potential benefits and limitations. By exploring these mechanisms, this review aims to provide insights into how SGLT2is can be integrated into strategies for preventing the progression of atrial remodeling and HF, as well as the development of AF.

Epicardial adipose tissue (EAT), the visceral fat layer next to the myocardium, has become an important focus in heart failure with preserved ejection fraction (HFpEF). When enlarged and inflamed, EAT increases pericardial restraint, releases fibroinflammatory mediators, and disrupts myocardial energetics, thereby reproducing the high-pressure, exercise-intolerant HFpEF phenotype regardless of body mass index. Modern echocardiography, cardiac CT, and MRI, enhanced by artificial intelligence texture analytics, now enable precise depot-specific quantification, making EAT a measurable therapeutic target. Early interventional studies suggest that caloric restriction, bariatric surgery, SGLT2 inhibitors, GLP-1 receptor agonists, statins, PCSK9 antibodies, and colchicine can reduce EAT volume or alter its inflammatory profile, with concurrent improvements in haemodynamics and biomarkers. However, definitive outcome trials are still pending. Priority directions include standardising imaging cut-offs, mapping EAT immune–metabolic niches, and testing combined metabolic–inflammatory regimens to translate EAT modulation into precision therapy for HFpEF. This review aims to synthesise current mechanistic, diagnostic, and therapeutic insights on EAT in HFpEF and outline future research priorities.

Background: Heart failure with preserved ejection fraction (HFpEF) is increasingly prevalent worldwide due to ageing and comorbidities. Emerging evidence suggests that Philadelphia-negative chronic myeloproliferative neoplasms (MPNs), particularly those with JAK2 mutations, may contribute to the development of HFpEF, especially by promoting inflammation and increasing thrombotic risk. Methods: This prospective case–control study assessed 58 patients with Philadelphia-negative MPNs and 41 controls, by clinical, paraclinical, and echocardiographic evaluation, to diagnose diastolic dysfunction and HFpEF according to the ESC guideline criteria. Results: Patients with MPNs had a significantly higher prevalence of HFpEF compared to controls (p = 0.008), higher H₂FPEF scores (median 5 vs. 3, p < 0.001), and significant echocardiographic abnormalities, including a higher left ventricular mass index (LVMI) (100.1 vs. 76.6 g/m², p < 0.001), E/e’ (11.00 vs. 7.00, p < 0.001), and pulmonary artery systolic pressure (PASP) (26.0 vs. 7.42 mmHg, p < 0.001). Multivariable logistic regression models identified male sex (OR = 8.993, p = 0.001) and the presence of JAK2 mutation (OR = 5.021, p = 0.002) as independent risk factors for HFpEF in this population. Conclusions: Patients with chronic MPNs, particularly males and those with JAK2 mutations, are at an increased risk of HFpEF, highlighting the importance of routine cardiologic assessment to improve outcomes in this patient population.

Background: Atrial fibrillation (AF) is a common comorbidity in heart failure with preserved ejection fraction (HFpEF), yet the optimal rhythm control strategies and the emerging role of sodium–glucose cotransporter-2 inhibitors (SGLT2i) in maintaining sinus rhythm remain unclear. Methods: We conducted a single-centre, retrospective study of 120 consecutive HFpEF patients with paroxysmal or persistent AF, treated by electrical cardioversion, radiofrequency ablation (RFA), or cryoablation. The primary outcome was AF recurrence, with secondary outcomes including time to recurrence and the impact of SGLT2i on AF recurrence. Results: Both cryoablation (HR = 0.226, 95% CI: 0.089–0.573, p = 0.002) and RFA (HR = 0.293, 95% CI: 0.131–0.654, p = 0.003) were associated with lower AF recurrence rates and longer arrhythmia-free survival compared to electrical cardioversion. SGLT2i therapy was independently associated with fewer recurrences (HR = 0.421, 95% CI: 0.266–0.786, p = 0.007) and a 12-week extension of AF-free time. Conclusions: In HFpEF with AF, prioritising catheter ablation over cardioversion and combining rhythm control with SGLT2i improves rhythm durability.

Hepatosplenomegaly can occur in extrahepatic diseases such as Philadelphia-negative chronic myeloproliferative neoplasms (MPNs), which may involve the liver and vasculature. In myelofibrosis, extramedullary hematopoiesis can be present in the liver, even within hepatic sinusoids. Liver biopsies in MPN patients have shown platelet aggregates obstructing these sinusoids. Both liver and spleen stiffness are significantly higher in myelofibrosis, correlating with the severity of bone marrow fibrosis. Spleen stiffness is also elevated in myelofibrosis and polycythemia Vera compared to essential thrombocythemia. MPNs are a leading cause of splanchnic vein thrombosis in the absence of cirrhosis or local malignancy, especially in the presence of the JAK2V617F mutation. This mutation promotes thrombosis through endothelial dysfunction and inflammation. It is found in endothelial cells, where it enhances leukocyte adhesion and upregulates thrombogenic and inflammatory genes. Hepatic sinusoidal microthromboses in MPNs may contribute to portal hypertension and liver dysfunction. MPN therapies can also affect liver function. While hepatocytolysis has been reported, agents such as Hydroxycarbamide and Ruxolitinib exhibit antifibrotic hepatic effects in experimental models. Overall, MPNs are linked to chronic inflammation, increased thrombotic risk—particularly splanchnic thrombosis—and atherogenesis.