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Background: Visualizing the specific regions where atrial fibrillation (AF) is maintained is crucial for effective treatment, but it remains challenging in clinical practice. We aimed to address this challenge by developing a mapping approach focused on the cycle length (CL) and its gradient (CL‐gradient). Methods: In 105 patients undergoing initial ablation for persistent AF, pre‐ablation CARTOFINDER data were utilized to create maps based on three indicators: (1) CL, the atrial frequency during AF calculated using CARTOFINDER; (2) Short CL, encompassing CLs within 5 ms of the minimum CL; and (3) CL‐gradient, the CL range within a 6 mm radius. We evaluated the association between the AF termination through ablation and the measured values and patterns in each map. Results: AF termination occurred in 17 patients. The AF termination group exhibited the significant large maximum CL‐gradient (48.8 ms [interquartile range, 38.6–66.3], p <.001) and the short distance between the minimum CL site and the maximum CL‐gradient site (15.8 mm, [interquartile range, 6.0–23.2], p =.029). Of the 17 AF termination cases, 13 exhibited a CL distribution pattern characterized by a steep CL‐gradient near the minimum CL site (SG‐MCL), defined as the distance of less than 23.2 mm and the maximum CL‐gradient greater than 33.1 ms. In these AF termination cases, SG‐MCL was also correlated with the ablation area. Conclusions: The minimum CL area accompanied by significant CL gradients in the immediate vicinity may play a crucial role in sustaining AF. [ABSTRACT FROM AUTHOR]

Aims: Hospitalizations are common in patients with heart failure and are associated with high mortality, readmission and economic burden. Detecting early signs of worsening heart failure may enable earlier intervention and reduce hospitalizations. The HeartLogic algorithm is designed to predict worsening heart failure using diagnostic data from multiple device sensors. The main objective of this analysis was to evaluate the sensitivity of the HeartLogic alert calculation in predicting worsening heart failure events (HFEs). We also evaluated the false positive alert rate (FPR) and compared the incidence of HFEs occurring in a HeartLogic alert state to those occurring out of an alert state. Methods: The HINODE study enrolled 144 patients (81 ICD and 63 CRT‐D) with device sensor data transmitted via a remote monitoring system. HeartLogic alerts were then retrospectively simulated using relevant sensor data. Clinicians and patients were blinded to calculated alerts. Reported adverse events with HF symptoms were adjudicated and classified by an independent HFE committee. Sensitivity was defined as the ratio of the number of detected usable HFEs (true positives) to the total number of usable HFEs. A false positive alert was defined as an alert with no usable HFE between the alert onset date and the alert recovery date plus 30 days. The patient follow‐up period was categorized as in alert state or out of alert state. The event rate ratio was the HFE rate calculated in alert to out of alert. Results: The patient cohort was 79% male and had an average age of 68 ± 12 years. This analysis yielded 244 years of follow‐up data with 73 HFEs from 37 patients. A total of 311 HeartLogic alerts at the nominal threshold (16) occurred across 106 patients providing an alert rate of 1.27 alerts per patient‐year. The HFE rate was 8.4 times greater while in alert compared with out of alert (1.09 vs. 0.13 events per patient‐year; P < 0.001). At the nominal alert threshold, 80.8% of HFEs were detected by a HeartLogic alert [95% confidence interval (CI): 69.9%–89.1%]. The median time from first true positive alert to an adjudicated clinical HFE was 53 days. The FPR was 1.16 (95% CI: 0.98–1.38) alerts per patient‐year. Conclusions: Results suggest that signs of worsening HF can be detected successfully with remote patient follow‐up. The use of HeartLogic may predict periods of increased risk for HF or clinically significant events, allowing for early intervention and reduction of hospitalization in a vulnerable patient population. [ABSTRACT FROM AUTHOR]

Identifying specific markers of adipose stem and progenitor cells (ASPCs) in vivo is crucial for understanding the biology of white adipose tissues (WAT). PDGFRα‐positive perivascular stromal cells represent the best candidates for ASPCs. This cell lineage differentiates into myofibroblasts that contribute to the impairment of WAT function. However, ASPC marker protein(s) that are functionally crucial for maintaining WAT homeostasis are unknown. We previously identified Meflin as a marker of mesenchymal stem cells (MSCs) in bone marrow and tissue‐resident perivascular fibroblasts in various tissues. We also demonstrated that Meflin maintains the undifferentiated status of MSCs/fibroblasts. Here, we show that Meflin is expressed in WAT ASPCs. A lineage‐tracing experiment showed that Meflin+ ASPCs proliferate in the WAT of obese mice induced by a high‐fat diet (HFD), while some of them differentiate into myofibroblasts or mature adipocytes. Meflin knockout mice fed an HFD exhibited a significant fibrotic response as well as increases in adipocyte cell size and the number of crown‐like structures in WAT, accompanied by impaired glucose tolerance. These data suggested that Meflin expressed by ASPCs may have a role in reducing disease progression associated with WAT dysfunction. [ABSTRACT FROM AUTHOR]

For many years, the significance of cardiac lymphatic vessels was largely overlooked in clinical practice, with little consideration given to their role in the pathophysiology or treatment of cardiac diseases. However, recent research has brought renewed attention to these vessels, progressively illuminating their function and importance within the realm of cardiovascular science. Experimental studies, particularly those utilizing animal models of cardiac disease, have demonstrated a clear relationship between cardiac lymphatic vessels and both the pathogenesis and progression of these conditions. These findings have prompted a growing interest in potential therapeutic applications that specifically target the cardiac lymphatic system. Conversely, while clinical investigations into cardiac lymphatics remain limited, recent studies have begun to explore their identification through specific surface markers, as well as the expression dynamics of lymphangiogenic factors. These studies have increasingly highlighted associations of lymphatic dysfunction with inflammation and fibrosis, both of which negatively impact cardiac function and remodeling across various pathological states. Despite these advances, comprehensive reviews of the current knowledge regarding the cardiac lymphatic vasculature, particularly within specific disease contexts, remain scarce. This review aims to address this gap by providing a detailed synthesis of existing reports, encompassing both animal model research and studies on human clinical specimens, with a special focus on the role of cardiac lymphatic vessels in different disease states. [ABSTRACT FROM AUTHOR]

Chronic fibrotic tissue disrupts various organ functions. Despite significant advances in therapies, mortality and morbidity due to heart failure remain high, resulting in poor quality of life. Beyond the cardiomyocyte-centric view of heart failure, it is now accepted that alterations in the interstitial extracellular matrix (ECM) also play a major role in the development of heart failure. Here, we show that protein kinase N (PKN) is expressed in cardiac fibroblasts. Furthermore, PKN mediates the conversion of fibroblasts into myofibroblasts, which plays a central role in secreting large amounts of ECM proteins via p38 phosphorylation signaling. Fibroblast-specific deletion of PKN led to a reduction of myocardial fibrotic changes and cardiac dysfunction in mice models of ischemia-reperfusion or heart failure with preserved ejection fraction. Our results indicate that PKN is a therapeutic target for cardiac fibrosis in heart failure. Despite significant advances in therapies, mortality and morbidity resulting from heart failure remain high. Here, the authors show that fibroblast-specific deletion of Protein kinase N (PKN) reduces myocardial fibrotic changes, indicating PKN as a potential therapeutic target for heart failure. [ABSTRACT FROM AUTHOR]

Background: The fibrosis‐5 (FIB‐5) index is a noninvasive marker for assessing the progression of liver fibrosis and predictor in patients with heart failure (HF). This study investigated the association between the FIB‐5 index and response to cardiac resynchronization therapy (CRT) and evaluated its predictive value for prognosis. Methods: In total, 203 patients who underwent CRT/CRT‐defibrillator (CRT‐D) implantation were retrospectively included. The FIB‐5 index was calculated using blood samples obtained before and after CRT/CRT‐D. Response to CRT was defined as a relative reduction in left ventricular end‐systolic volume of ≥15% 6 months after CRT/CRT‐D. We compared the prognosis after CRT/CRT‐D between the groups according to the FIB‐5 index. Results: One hundred and twenty‐three patients (61%) responded to CRT. The responder group demonstrated a significantly higher FIB‐5 index than the nonresponder group (−2.76 ± 3.85 vs. −4.67 ± 3.29, p < 0.001). Receiver‐operating characteristic analysis demonstrated that the area under the curve of the FIB‐5 index was 0.660 with a cutoff value of −4.00 for responders. In multivariate analysis, FIB‐5 index ≥ −4.00 was an independent predictor for CRT response (odds ratio: 3.665, p = 0.003), in addition to QRS duration ≥ 150 ms and echocardiographic dysynchrony. The FIB‐5 index increased significantly after 6 months in the responder group but not in the nonresponder group. The FIB‐5 index ≥ −4.00 group showed a significantly better prognosis for cardiac death, HF hospitalization, and composite endpoint than the FIB‐5 index < −4.00 group. Conclusion: The FIB‐5 index in addition to classical predictors may be a useful marker for predicting response to CRT. [ABSTRACT FROM AUTHOR]

Background Guidelines recommend optimal medical therapy before cardiac resynchronization therapy (CRT) implantation. Herein, we report the potential effect of sodium-glucose cotransporter-2 inhibitors (SGLT2is) in improving the QRS duration and volume reduction in a patient with complete left bundle branch block (CLBBB) and reduced cardiac function. Case summary A 68-year-old man with a history of ischaemic cardiomyopathy and decreased cardiac function had exacerbation of heart failure (HF) at an outpatient clinic. His QRS duration increased remarkably with a CLBBB of 143 ms on an electrocardiogram, and left ventricular desynchrony was assessed by echocardiography, suggesting an indication of CRT implantation. Administration of an SGLT2i and multimodal treatment for HF stabilized his HF condition and improved the QRS duration and volume reduction thereafter. The CLBBB recovered to incomplete LBBB with a QRS duration of 112 ms on electrocardiography after 6 months. The patient has been stably followed up with continuous medications, including SGLT2i, without requiring CRT implantation or worsening of HF for 12 months. Discussion This case presents a unique scenario wherein electrical and mechanical reverse remodelling occurred in a patient with systolic HF and CLBBB, highlighting the potential benefits of SGLT2i in HF management. It may be important to carefully consider CRT indications when seeking other options to treat HF conditions and recognize an unusual phenomenon of reverse LBBB in clinical cases. [ABSTRACT FROM AUTHOR]