Structural remodeling of the left atrium contributes to the progression of heart failure (HF), even in the absence of atrial fibrillation (AF). However, the underlying mechanisms and extent of atrial remodeling across the spectrum of left ventricular ejection fraction (LVEF) remain poorly defined. This study aimed to characterize anatomical and functional left atrial changes using multimodal imaging and biomarker profiling in patients with HF without AF. A total of 264 ambulatory patients with HF and no prior AF, all under continuous rhythm monitoring, were prospectively studied. All underwent transthoracic echocardiography with functional analysis of the left atrium and plasma biomarker assessment. Patients were classified according to LVEF into three groups: preserved, mildly reduced, and reduced. Correlations between echocardiographic parameters and circulating biomarkers were analyzed. Patients with reduced LVEF showed larger atrial volumes, lower reservoir strain, impaired conduit function, and higher atrial stiffness. Biomarker profiling revealed increased levels of natriuretic peptides and extracellular matrix proteins, along with moderate elevations in inflammation-related markers. Atrial strain was significantly correlated with markers of fibrosis, inflammation, and wall stress, particularly in patients with lower LVEF. In patients with HF without AF, the severity of atrial remodeling increases as LVEF declines and aligns with biomarkers of hemodynamic overload and fibrosis. The integration of imaging and molecular parameters may improve risk stratification and phenotyping in HF.

Heart failure with reduced ejection fraction (HFrEF) causes reduced functional capacity, impaired quality of life, and frequent rehospitalisation. Although guidelines recommend cardiac rehabilitation (CardRehab), referral rates remain low. The MEDIAN Heart Failure Registry evaluated short- and midterm outcomes of inpatient CardRehab in routine practice. A prospective multicentre registry included 808 patients with clinically stable HFrEF (LVEF ≤ 40%) undergoing inpatient cardiac rehabilitation across 17 German centres (2019-2020). Clinical outcomes-6-min walk test, bicycle ergometry, echocardiographic LVEF, NYHA class, NT-proBNP (subset), and patient-reported outcomes (KCCQ, HADS)-were assessed at admission, discharge, and 6months post-discharge. A structured follow-up survey evaluated adherence to lifestyle changes and the sustainability of effects after the 22.8-day inpatient stay. A total of 808 patients (mean age, 65years; 16.6% females) showed significant improvements in physical and psychosocial parameters. Mean LVEF increased from 31.1% (SD 9.0) to 35.9% (SD 10.7; p < 0.01), mean 6-min walk distance from 306m (SD 136) to 388m (SD 158; p < 0.01), and mean bicycle ergometry from 27.8 W (SD 15.4) to 49.5 W (SD 26.4; p < 0.01). Mean NT-proBNP decreased (p < 0.01). KCCQ and HADS scores improved significantly. Inpatient mortality rate during rehabilitation was 0.6% (5/808), and the rehospitalisation rate due to heart failure was 2.8% (23/808). There were two documented cancellations of rehabilitation. At 6-month follow-up, benefits remained stable with high adherence to recommended behaviours. Cardiac rehabilitation was associated with improvements in physical capacity, left ventricular function, psychological well-being, and quality of life in patients with chronic heart failure, alongside low observed rehospitalisation rates during follow-up.

Among patients with atrial fibrillation, those with a recent stroke are at significantly higher risk of recurrence than those without. Catheter ablation is expected to reduce the risk of recurrent stroke, heart failure, and mortality in these patients. To evaluate the efficacy and safety of catheter ablation added to standard therapy for reducing the risk of recurrent stroke or composite outcomes in patients with atrial fibrillation and a recent history of stroke. The Stroke Secondary Prevention With Catheter Ablation and Edoxaban for Patients With Nonvalvular Atrial Fibrillation (STABLED) study was an open-label, parallel-group, randomized clinical trial. Patients were enrolled from January 2018 to March 2021 and observed until March 2024. This study was conducted at 45 sites in Japan. Patients aged 20 years or older and 85 years or younger and those with a definitive diagnosis of nonvalvular atrial fibrillation on electrocardiogram, a history of ischemic stroke, currently receiving or scheduled to receive edoxaban, and having a modified Rankin Scale score of 3 or less were enrolled. Study data were analyzed from September 2024 to July 2025. Patients were randomized to receive standard therapy or standard therapy plus catheter ablation (after ≥4 weeks of edoxaban, within 1-6 months of index stroke onset). The primary end point was a composite of recurrent ischemic stroke, systemic embolism, all-cause death, and hospitalization for heart failure. Safety related to the catheter ablation procedure was assessed. A total of 251 patients were enrolled and 249 (mean [SD] age, 71.7 [7.5] years; 187 male [75.1%]) were randomized (standard therapy, 124; standard therapy plus catheter ablation, 125). Median follow-up was greater than 3 years. The primary end point occurred at rates of 4.9% and 5.6% per person-year (hazard ratio, 1.11; 95% CI, 0.62-2.01) with standard therapy vs catheter ablation, respectively. The respective mortality rates were 1.0 and 2.8 per 100 person-years. Two ablation-related adverse events (cardiac tamponade, stroke) were reported (0.8% each). In patients with atrial fibrillation and a recent stroke history, standard therapy plus catheter ablation did not significantly reduce the risk of the primary composite end point. The observed event rate was lower than anticipated, suggesting that the study was underpowered to detect clinically meaningful differences. ClinicalTrials.gov Identifier: NCT03777631.

Pregnancy triggers major cardiovascular adaptations to meet the demands of the growing fetus. While these changes are well tolerated in healthy individuals, they can reveal or exacerbate underlying cardiovascular disease. This mini literature review explores the impact of chronic hypertension and obesity on cardiovascular physiology during and after pregnancy. Both conditions heighten the risk of complications such as heart failure, hypertensive disorders, and long-term cardiovascular disease. Chronic hypertension contributes to structural heart changes and impairs the heart's ability to manage increased volume demands. Obesity promotes inflammation, insulin resistance, and cardiac remodeling, further straining the cardiovascular system. Together, these comorbidities amplify the hemodynamic burden of pregnancy and increase the likelihood of adverse outcomes. Despite these risks, many patients do not receive adequate cardiovascular monitoring or postpartum follow-up. This review highlights the need for early risk assessment, individualized management, and multidisciplinary care to optimize maternal and fetal outcomes. Pregnancy offers a unique opportunity to identify and address cardiovascular risk, with benefits that extend well beyond the perinatal period.

Utilization of ivabradine in the pediatric population has been centered on the goal of chronotropic control in patients with arrhythmias and heart failure. Tachycardia is known to be detrimental when it impairs hemodynamics by increasing myocardial oxygen demand, increasing ventricular end-diastolic pressures, and decreasing cardiac output in certain patients. The acute hemodynamic effects of ivabradine have not yet been studied in real time. This study was performed leveraging the Sickbay platform (Medical Informatics Company, Houston, TX). The primary aim of this study was to characterize the effect of enteral ivabradine on heart rate in patients in a pediatric cardiac intensive care unit within 24 hours of initiation. Secondary aims were to characterize the effects of ivabradine on arterial saturation, respiratory rate, mean arterial blood pressure, central venous pressure, and renal near infrared spectroscopy for the same time frame. Heart rate decreased approximately 17% in the first 15 hours after ivabradine administration. Changes were seen in the secondary aims that varied depending on time after first and second doses. Specifically, decreases in central venous pressure and increased renal tissue oxygen saturation (rSO2) were observed by the end of the 24 hours. Ivabradine seems safe in pediatric patients. It is associated with 3 distinct hemodynamic response phases: the first phase is associated with decreased heart rate and unchanged systemic oxygen delivery, the second phase is associated with increased heart rate and worsened systemic oxygen delivery, and the third phase being associated with decreased heart rate and improved systemic oxygen delivery. These phases coincide with the pharmacokinetic properties of ivabradine.

Cardiac aging is associated with progressive cardiac fibrosis and dysfunction, yet the underlying mechanisms remain incompletely understood. Extrachromosomal circular DNA (eccDNA) has been reported to participate in tumor and age-related genomic instability, while its role in cardiac fibrosis during aging remains to be fully elucidated. In this study, circular DNA sequencing and RNA seqencing were performed to analyze eccDNA profiles in young and aged cardiac tissues. The number of eccDNAs in the cardiac tissue of aged mice is higher than that in young mice. Combining the annotation of eccDNAs and the key genes related to aging identified in the transcriptome, we identified sterile alpha and TIR motif containing 1 (Sarm1), a key regulator of NAD+ metabolism and neurodegeneration located in eccDNAs, as a novel driver of cardiac aging via pro-fibrotic signaling. In aged mice, Sarm1 knockdown significantly restored cardiac function and reduced fibrosis. Conversely, Sarm1 accelerated cardiac aging phenotypes in young Sarm1-overexpressing transgenic mice. Mechanistically, co-immunoprecipitation combined with mass spectrometry identified TGF-β-Smad2/3 as the dominant pathway, with pharmacological inhibition by SIS3 abolishing Sarm1-driven Smad2/3 phosphorylation. Our findings reveal that Sarm1-containing eccDNA drives cardiac aging by amplifying pro-fibrotic signaling through the TGF-β-Smad2/3 pathway, proposing eccDNAs clearance and Sarm1 inhibition as novel therapeutic strategies for aging-related cardiac fibrosis.

Relevance. Post-infarction chronic heart failure contributes to the development of atrial fibrillation, the most common form of arrhythmia. The search for new drugs with pronounced antiarrhythmic activity is currently relevant. Purpose of the study. To study the sequence of atrial epicardial depolarization in rats with post-infarction chronic heart failure after long-term administration of fabomotizole. Methods. The sequence of atrial epicardial depolarization in rats with post-infarction chronic heart failure caused by anterior transmural myocardial infarction and sham-operated animals was studied using synchronous multichannel cardiac electrochronotopography after a course of fabomotizole administration. Results. Post-infarction chronic heart failure provokes the appearance of an additional excitatory focus in the pulmonary vein lacunae of the left atrium, which is a predictor of atrial arrhythmogenicity. Fabomotizole suppresses an additional arrhythmogenic focus of excitation in the area where the pulmonary veins enter the left atrium, minimizing the risk of developing atrial tachyarrhythmias, including atrial fibrillation.

Bridging traditions and evidence: Qiliqiangxin in the evolving landscape of heart failure therapy

Cardiovascular disease remains the leading cause of death worldwide, with its disease burden continuing to rise. After cardiac injury, most commonly ischemia from myocardial infarction, irreversible loss of cardiomyocytes (CMs) occurs, and the damaged myocardium is replaced by fibroblast (Fib)-derived scar tissue. Because adult CMs have limited regenerative capacity, repair is limited, cardiac function progressively declines, and patients often develop heart failure. Direct cardiac reprogramming-converting Fibs into induced CM-like cells (iCMs)-has emerged as a promising strategy to restore contractile myocardium. Omics-based approaches have greatly advanced understanding of the mechanisms that enable or hinder iCM generation. Single-cell transcriptomics have delineated gene expression trajectories and intermediate cell states, while epigenomic studies have revealed how chromatin accessibility, histone modifications, and DNA methylation shape cell fate conversion. Post-transcriptional analyses further highlight the importance of RNA processing and translational control, and proteomic profiling has demonstrated rapid remodeling of protein networks and paracrine signaling during reprogramming. In parallel, metabolic studies have linked shifts in metabolite flux to iCM maturation. Together, these multi-omics investigations provide an integrated framework for defining both barriers and facilitators of Fib-to-iCM conversion. This review synthesizes recent omics-based insights into direct cardiac reprogramming and discusses future directions for advancing its clinical application.

Left atrial (LA) volume and strain parameters have been associated with cardiovascular outcomes in several cardiac pathologies, yet their role in predicting major adverse cardiovascular events (MACE) in kidney transplant (KT) recipients has not been explored. We retrospectively reviewed the records of adult KT recipients from our institution (2015-2024). We utilized baseline echocardiograms routinely acquired during KT workup to measure LA volumetrics and strain. MACE was the study's primary endpoint, defined as cardiovascular death, nonfatal myocardial infarction, stroke, major arrhythmias or heart failure hospitalization. Logistic regression, Kaplan-Meier and Cox proportional hazards regression were performed to evaluate the association between LA parameters and MACE. Of 518 patients who underwent kidney transplant, 377 were in sinus rhythm with an acceptable quality echocardiogram (male, 56.7%; mean age 53.7 ± 13.1 years). Over a median follow up duration of 5.3 ± 2.3 years from KT, 82 patients reached the study endpoint. Kaplan-Meier analysis showed significantly lower MACE-free survival in patients with abnormal LA strain. After adjusting for confounding variables in the Cox Proportional Hazards model, of all LA parameters, lower LAScd (HR 0.94, 95% CI 0.89-0.98, p = 0.003), and LASr (HR 0.97, 95% CI 0.94-0.995, p = 0.02) were independently associated with MACE. In this retrospective single center study, LA strain parameters particularly LASr and LAScd were independently associated with MACE after KT. LA strain might have a role in risk stratification in this population.

Early complications after cardiac implantable electronic device (CIED) implantation remain clinically relevant and have been widely examined in large registry studies. Advanced age, comorbidities, device complexity, and antithrombotic therapy are recognized predictors of early complications. This study planned to examine the effect of sex on early (≤ 30 days) device-related complications and to determine independent predictors of early major adverse cardiac events (MACE). This retrospective, single-center study enrolled 1807 sequential patients (729 women, 1078 men) undergoing pacemaker, implantable cardioverter-defibrillator, or cardiac resynchronization therapy implantation. Early MACE was described as consisting of pocket hematoma, pneumothorax, pericardial effusion/tamponade, and device-related infection within 30 days. Univariable and multivariable logistic regression analyses were conducted to determine autonomous prognostic factors. Early MACE occurred in 26 (3.6%) women and 41 (3.8%) men (p = 0.893). Device type distribution differed significantly by sex, with defibrillators more frequently implanted in men and pacemakers and resynchronization devices in women (all p < 0.001). Sex was not independently related to early MACE (OR 1.28, 95% CI 0.77-2.13; p = 0.337). Higher PORT scores (OR 1.06, p = 0.035), higher white blood cell counts (OR 1.09, p = 0.004), lower hemoglobin levels (OR 0.86, p = 0.024), and the presence of heart failure (OR 0.35, p = 0.002) remained independent predictors of early MACE. Early CIED-related complications were infrequent and occurred at similar rates in women and men. Sex was not an independent predictor of early MACE; instead, overall clinical risk burden and systemic factors were the primary determinants of early adverse outcomes.

Diabetic cardiomyopathy (DCM) describes the abnormality of myocardial structure and function caused by diabetes, and Yes-associated protein (Yap) is linked to various cardiovascular diseases, modulating remodeling and cardiac function in hearts, but its role in DCM is unclear. How Yap affects myocardial structure and function in mice with type 2 diabetes mellitus and the underlying pathways were investigated. High glucose or high glucose plus palmitic acid levels enhance Yap activity, thereby promoting miR-22-3p expression and inhibiting sirtuin 1 (Sirt1) expression. The Yap-miR-22-3p-Sirt1 axis plays critical roles in the cause of DCM. The molecular pathways investigated offer promising targets for therapeutic intervention against DCM and provide new insights into the development of innovative treatment strategies to combat cardiac dysfunction in patients with diabetes.

Inter-specialty differences and knowledge gaps in acute and advanced heart failure care.

Differences in guideline directed medical therapy for rural and non-rural Veterans with heart failure with reduced ejection fraction.

To retrospectively evaluate hypochloremia as a predictor of poor outcomes for dogs with congestive heart failure (CHF). A single-institution retrospective study including dogs diagnosed with CHF between 2014 and 2024. Biochemical variables, medications, and outcome data were extracted from medical records at the first recheck after the initial CHF episode. Exclusion criteria were active CHF, absence of serum chloride concentration (s[Cl]) on bloodwork, reliance on point-of-care bloodwork alone, major interventional procedures (eg, mitral valve repair), and clinically important vomiting or diarrhea. Dogs were grouped by s[Cl] < 100 or ≥ 100 mEq/L. Associations between s[Cl] < 100 mEq/L, biochemical variables, medications, and risk of death were evaluated with a Cox proportional hazards model. Survival was assessed with a Kaplan-Meier analysis and compared with a log-rank test. A total of 292 stable CHF dogs were included (229 degenerative valve disease, 31 dilated cardiomyopathy, 21 congenital heart disease, 6 pulmonary hypertension, and 5 arrhythmogenic cardiomyopathy). Median s[Cl] was 106.5 mEq/L (range, 85.0 to 119.0 mEq/L). Dogs with s[Cl] < 100 mEq/L had a significantly increased risk of death (HR, 2.649; 95% CI, 1.265 to 5.311) and shortened survival (median survival, 115 days) compared to dogs with s[Cl] ≥ 100 mEq/L (median survival, 196 days). No other biochemical variables or medications were significantly associated with survival. Moderate to severe hypochloremia (s[Cl] < 100 mEq/L) in dogs with stable CHF is associated with worse survival compared to dogs with s[Cl] ≥ 100 mEq/L. These findings support clinical efforts to correct and maintain serum chloride concentrations above 100 mEq/L in dogs with CHF.

To explore associations among expanded field swept-source optical coherence tomography angiography metrics and the development of myocardial infarction, congestive heart failure (CHF), and all-cause mortality in diabetic patients with and without diabetic retinopathy (DR). Baseline swept-source optical coherence tomography angiography images (6 × 6 mm, Montage 15 × 15 mm) were assessed for quantitative and qualitative metrics to identify parameters associated with myocardial infarction, CHF, and all-cause mortality. One hundred and seventy-eight eyes from 119 adults with diabetes without DR or with nonproliferative DR or proliferative DR were included (median 44 months, range 3-57 months). Eleven participants (9.2%) had a cardiovascular event (six myocardial infarction, five CHF) and seven (5.9%) died. Neovascularization vessel density (HR = 44.0, 95% confidence interval [CI]: 1.0-1,861.2, P = 0.048) and vitreous hemorrhage (HR = 39.7, 95% CI: 4.0-392.8, P = 0.002) were associated with CHF. Vitreous hemorrhage (HR = 13.5, 95% CI: 3.0-61.2, P = 0.001) and prior treatment with anti-vascular endothelial growth factor injections and panretinal photocoagulation (HR = 11.4, 95% CI: 2.0-66.3, P = 0.007) were associated with cardiovascular disease (CHF or myocardial infarction). Increased skeletonized vessel density of the deep capillary plexus (HR = 1.2, 95% CI: 1.0-1.5, P = 0.026) was associated with mortality. Neovascularization vessel density and skeletonized vessel density of the deep capillary plexus on swept-source optical coherence tomography angiography are associated with cardiovascular disease and mortality in patients with DR. These exploratory findings suggest that swept-source optical coherence tomography angiography may be a useful noninvasive tool to identify diabetic patients at increased risk of cardiovascular disease and death.

Neutrophil-to-lymphocyte ratio and C-reactive protein in patients admitted with Acute Dyspnoea suspected of acute heart failure.

A Mendelian randomization study with bioinformatics analysis reveals gut microbiota mediates in heart failure and Alzheimer's disease via BAFF-R.

Targeting LUM-mediated inflammatory cell communication and fibroblast apoptosis with SFI in Heart Failure.

Heart failure (HF) affects millions of individuals worldwide and shows an increasing trend, constituting a serious public health issue. Considerable attention has been paid to the screening, diagnosis, risk prediction, treatment, and prognosis of HF. Although many guidelines for the management of HF have been proposed in recent years, the efficacy of evidence-based treatments seems to vary among patients. Therefore, the era of "one-size-fits-all" approaches is drawing to a close, and the concepts of precision medicine and individualized medicine are gradually taking root. Artificial intelligence (AI) is an emerging discipline in the rapidly growing field of computer science. It has now become deeply involved in all aspects of cardiovascular disease research, with particular relevance to HF, though its translation into clinical practice is yet to be fully realized. Although the use of AI in cardiovascular disease (CVD) and HF patient care, as well as cardiac resynchronization therapy (CRT), has been extensively discussed, a discussion from the standpoint of all aspects of HF clinical process is lacking. This review provides a comprehensive overview of the use of AI in HF in specific scenarios, including patient diagnosis, subtyping, prognostic assessment, pre- and post-treatment evaluation, and telecare. It also presents the prospects and challenges for the development of AI in the field of HF, with the expectation that a mature AI diagnosis and treatment system adapted to clinical practice will be developed in the future through in-depth research and validation. This review summarizes the application of AI in various links of HF management from diagnosis to telecare, and analyzes its current application limitations, existing challenges and future research directions, aiming to provide a reference for the subsequent clinical transformation and research optimization of AI in the HF field.