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High levels of homocysteine (Hcy) have been linked with adverse cardiovascular outcomes, such as arrhythmias and stroke. In the context of paroxysmal atrial fibrillation (PAF), hyperhomocysteinemia has been demonstrated to be an independent predictor of future events. The aim of this report was to address the potential value of Hcy levels in predicting future paroxysms of atrial fibrillation (AF), as well as to identify the potential mechanisms of action. We searched PubMed and the Cochrane Database on 16 January 2022. Keywords used were homocysteine or hyperhomocysteinemia paired with a total of 67 different keywords or phrases that have been implicated with the pathogenesis of AF. We included primary reports of clinical and non-clinical data in the English language, as well as systematic reviews with or without meta-analyses. We placed no time constraints on our search strategy, which yielded 3748 results. Following title review, 3293 reports were excluded and 455 reports were used for title and abstract review, after which 109 reports were finally used for full-text review. Our review indicates that Hcy levels seem to hold a predictive value in PAF. Herein, potential mechanisms of action are presented and special considerations are made for clinically relevant diagnostic procedures that could complement plasma levels in the prediction of future PAF events. Finally, gaps of evidence are identified and considerations for future clinical trial design are presented.

Iron deficiency (ID) is a prevalent comorbidity in heart failure (HF), affecting 37–75% of patients and contributing significantly to symptom burden and adverse outcomes independent of anemia status. Current diagnostic criteria for ID in HF include absolute deficiency (ferritin <100 μg/L) and functional deficiency (ferritin 100–299 μg/L with transferrin saturation <20%). Major clinical trials including AFFIRM-AHF, IRONMAN, HEART-FID, and FAIR-HF2 have demonstrated that intravenous iron therapy, particularly ferric carboxymaltose, reduces HF hospitalizations and improves quality of life and exercise capacity. The 2023 European Society of Cardiology guidelines recommend intravenous ferric carboxymaltose for symptomatic iron-deficient patients with heart failure with reduced ejection fraction. Despite these advances, significant knowledge gaps remain regarding optimal diagnostic approaches, the relationship between ID and ferroptosis in cardiac tissue, and the efficacy of newer iron formulations. This review synthesizes current understanding of ID in HF and highlights emerging therapeutic strategies.

Background/Objectives: Iron deficiency (ID) is a common and prognostically relevant comorbidity in heart failure with reduced ejection fraction (HFrEF). It contributes to reduced functional status, exercise capacity, and survival. Intravenous ferric carboxymaltose (FCM) improves symptoms, but its effect on cardiac structure and function remains incompletely understood. The aim of this study was to assess the impact of intravenous FCM on echocardiographic indices of left ventricular (LV), left atrial (LA), and right ventricular (RV) morphology and function in HFrEF patients with ID and determine whether these changes correlate with improvements in exercise capacity. Methods: This sub-analysis of the RESAFE-HF registry (NCT04974021) included 86 HFrEF patients with ID (median age 71.8 years, 83% male). Transthoracic echocardiography was performed at baseline and 12 months post-FCM. Parameters assessed included LV ejection fraction (LVEF), LV global longitudinal strain (GLS), LV diastolic function grade, LAVi, LA strain, TAPSE, and RV free wall strain (FWS). Peak VO2 was measured to assess exercise capacity. Results: LVEF improved from 29.3 ± 7.8% to 32.5 ± 10.6% (p < 0.001), LV GLS from −7.89% to −8.62%, and the LV diastolic dysfunction grade improved (p < 0.001). LAVi, peak LA strain, TAPSE, and RV FWS also showed significant improvement. Peak VO2 increased from 11.3 ± 3.2 to 12.1 ± 4.1 mL/min/kg (p < 0.001). Improvements in LVEF, RV FWS, and LV GLS were independent predictors of VO2 increase (p < 0.001, p < 0.001, and p = 0.01, respectively), explaining 42% of the variance. Conclusions: FCM therapy improves biventricular and atrial function, with echocardiographic gains correlating with an enhanced exercise capacity in HFrEF patients with ID.

Aims The Iron Intravenous Therapy in Reducing the burden of Severe Arrhythmias in HFrEF (RESAFE‐HF) registry study aims to provide real‐word evidence on the impact of intravenous ferric carboxymaltose (FCM) on the arrhythmic burden of patients with heart failure with reduced ejection fraction (HFrEF), iron deficiency (ID), and implanted cardiac implantable electronic devices (CIEDs). Methods and results The RESAFE‐HF (NCT04974021) study was designed as a prospective, single‐centre, and open‐label registry study with baseline, 3, 6, and 12 month visits. Adult patients with HFrEF and CIEDs scheduled to receive IV FCM as treatment for ID as part of clinical practice were eligible to participate. The primary endpoint is the composite iron‐related endpoint of haemoglobin ≥ 12 g/dL, ferritin ≥ 50 ng/L, and transferrin saturation > 20%. Secondary endpoints include unplanned HF‐related hospitalizations, ventricular tachyarrhythmias detected by CIEDs and Holter monitors, echocardiographic markers, functional status (VO2 max and 6 min walk test), blood biomarkers, and quality of life. In total, 106 patients with a median age of 72 years (14.4) were included. The majority were male (84.9%), whereas 92.5% of patients were categorized to New York Heart Association II/III. Patients' arrhythmic burden prior to FCM administration was significant—19 patients (17.9%) received appropriate CIED therapy for termination of ventricular tachyarrhythmia in the preceding 12 months, and 75.5% of patients have frequent, repetitive multiform premature ventricular contractions. Conclusions The RESAFE‐HF trial is expected to provide evidence on the effect of treating ID with FCM in HFrEF based on real‐world data. Special focus will be given on the arrhythmic burden post‐FCM administration.

Purpose Heart failure (HF) and atrial fibrillation (AF) are highly prevalent in hemodialysis. They are well-known significant modifiers of the disease associations with cardiovascular outcomes, but there is a lack of evidence regarding the effects of HF and AF on cardiorespiratory fitness. This study is the first to examine the possible association of the presence of HF and AF with exercise intolerance in patients undergoing hemodialysis. Methods This analysis included 40 sex- and age-matched participants [10 hemodialysis patients with HF or AF, 10 hemodialysis patients without HF or AF, 10 patients with HF or AF without chronic kidney disease (CKD) and 10 healthy controls] that underwent CPET and spirometry examinations. The total of patients with HF had preserved ejection fraction. Results VO2peak(ml/kg/min) showed a graded increase between hemodialysis patients with HF or AF, hemodialysis patients without HF or AF, non-CKD patients with HF or AF and controls (13.17 ± 2.45 vs 15.26 ± 3.29 vs 19.64 ± 5.84 vs 25.11 ± 6.94 ml/kg/min, p  < 0.001); VO2peak(ml/min) followed the same pattern (1172 ± 197 vs 1269 ± 314 vs 1817 ± 583 vs 1952 ± 592 ml/min respectively, p  = 0.001). VO2peak(%predicted), VO2AT(ml/kg/min), VO2AT(ml/min) and maximal work load significantly differed between the study groups, with a tendency for higher values from hemodialysis patients to non-CKD patients with HF or AF and to healthy controls. FEV1 and FVC levels were similar between the study groups. In the whole population, VO2peak(ml/kg/min) showed a positive correlation with hemoglobin ( r  = 0.663, p  < 0.001) and negative correlations with high-sensitivity cardiac troponin I ( r  = − 0.493, p  = 0.001) and BNP ( r  = − 0.479, p  = 0.002). Conclusion Hemodialysis patients have low exercise tolerance, and the presence of HF or AF is associated with further decreased values of VO2peak, the most important determinant of cardiorespiratory fitness.

Heart failure (HF) remains a major public health challenge, while HF self-care is particularly challenging. Mobile health (mHealth)-based interventions taking advantage of smartphone technology have shown particular promise in increasing the quality of self-care among these patients, and in turn improving the outcomes of their disease. The objective of this study was to co-develop with physicians, patients with HF, and their caregivers a patient-oriented mHealth app, perform usability assessment, and investigate its effect on the quality of life of patients with HF and rate of hospitalizations in a pilot study. The development of an mHealth app (The Hellenic Educational Self-care and Support Heart Failure app [ThessHF app]) was evidence based, including features based on previous clinically tested mHealth interventions and selected by a panel of HF expert physicians and discussed with patients with HF. At the end of alpha development, the app was rated by mHealth experts with the Mobile Application Rating Scale (MARS). The beta version was tested by patients with HF, who rated its design and content by means of the Post-Study System Usability Questionnaire (PSSUQ). Subsequently, a prospective pilot study (THESS-HF [THe Effect of a Specialized Smartphone app on Heart Failure patients' quality of self-care, quality of life and hospitalization rate]) was performed to investigate the effect of app use on patients with HF over a 3-month follow-up period. The primary endpoint was patients' quality of life, which was measured with the Kansas City Cardiomyopathy Questionnaire (KCCQ) and the 5-level EQ-5D version (EQ-5D-5L). The secondary endpoints were the European Heart Failure Self-care Behavior Scale (EHFScBS) score and the hospitalization rate. A systematic review of mHealth-based HF interventions and expert panel suggestions yielded 18 separate app features, most of which were incorporated into the ThessHF app. A total of 14 patients and 5 mHealth experts evaluated the app. The results demonstrated a very good user experience (overall PSSUQ score 2.37 [SD 0.63], where 1 is the best, and a median MARS score of 4.55/5). Finally, 30 patients (male: n=26, 87%) participated in the THESS-HF pilot study (mean age 68.7 [SD 12.4] years). A significant increase in the quality of self-care was noted according to the EHFScBS, which increased by 4.4% (SD 7.2%) (P=.002). The mean quality of life increased nonsignificantly after 3 months according to both KCCQ (mean increase 5.8 [SD 15] points, P=.054) and EQ-5D-5L (mean increase 5.6% [SD 15.6%], P=.06) scores. The hospitalization rate for the follow-up duration was 3%. The need for telehealth services and remote self-care management in HF is of vital importance, especially in periods such as the COVID-19 pandemic. We developed a user-friendly mHealth app to promote remote self-care support in HF. In this pilot study, the use of the ThessHF app was associated with an increase in the quality of self-care. A future multicenter study will investigate the effect of the app use on long-term outcomes in patients with HF.

As our therapeutic armamentarium for HFpEF is insufficient, research has been focusing on the potential beneficial effect of existing pharmaceutical regimens on this specific patient population. A series of RCTs have recently examined the impact of various pharmaceutical treatments with proven benefit in HFrEF, on the improvement of symptoms of HFpEF patients. This systematic review and meta-analysis comprised studies of adult patients with HFpEF and evaluated the impact of different cardiovascular acting medication on cardiorespiratory fitness, reflected by peak VO2 values measured during CPET. The primary outcome was difference between groups in the change of peak VO2 (ΔpeakVO2). Literature search involved PubMed/MEDLINE, Scopus and Web of Science databases. Our search identified 3634 records and 19 studies were included in qualitative analysis; 12 studies with 1341 patients were finally included in primary outcome analysis. ΔpeakVO2 between baseline and study-end did not significantly change after treatment with spironolactone, ivabradine, sildenafil, or oral inorganic nitrate and neither did difference in 6MWT distance after treatment with spironolactone. Spironolactone led to statistically significant reduction in E/E’ ratio study-end values (WMD − 1.64, 95%CI − 2.42 to − 0.86, I2 = 87%, p < 0.0001), as well as to a significant increase in MLHFQ values (WMD 0.75, 95%CI 0.02 to 1.48, I2 = 0%, p = 0.65), indicating deterioration in HRQoL among HFpEF patients. A series of established cardiovascular acting medication in HFrEF seems not to confer significant benefit in peak VO2 and 6MWT distance in HFpEF. Spironolactone is associated with improvements in diastolic function and with a significant deterioration in HRQoL of this population.

Background The contribution of atrial and ventricular function in neurocardiogenic syncope (NCS) pathophysiology is elusive. Hypothesis We assessed the influence of echocardiographic properties to the age of presentation and NCS recurrences. Methods We assigned 124 patients with symptoms suggesting NCS, to those with syncope initiation at age <35 (group A, n = 56) and >35 years (group B, n = 68). Echocardiographic indices were measured before head‐up tilt test (HUTT). Results A total of 55 had positive HUTT (44%) with a trend favoring group A (p = .08). Group A exhibited lower left atrial (LA) volume index (17 ± 6 vs. 22 ± 11 ml/m2, p = .015), higher LA ejection fraction (69 ± 10 vs. 63 ± 11%, p = .008), LA peak strain (reservoir phase 41 ± 13 vs. 31 ± 14%, p = .001, contraction phase 27 ± 11 vs. 15 ± 10%, p < .001) and LA peak strain rate (reservoir phase 1.83 ± 1.04 vs. 1.36 ± 0.96 1/s, p = .012, conduit phase 2.36 ± 1.25 vs. 1.36 ± 0.78 1/s, p = .001). Group A showed smaller minimum right atrial (RA) volume, better RA systolic function, superior left ventricular diastolic indices, and lower filling pressures. Group A patients were more likely to have >3 recurrences (82.0% vs. 50.1%, p < .05). Conclusions Patients with younger age of NCS onset and more syncopal recurrences manifest smaller LA and RA dimensions with distinct patterns of systolic and diastolic function and better LA reservoir and contraction properties. These findings may indicate an increased susceptibility to preload reduction, thereby triggering the NCS mechanism.

Atrial fibrillation (AF) is the most common sustained arrhythmia and a growing global health burden, yet conventional monitoring with Holter devices, event recorders and implantable loop recorders often fails to adequately capture recurrence. Rapid advances in digital health, wearable biosensors and artificial intelligence (AI) have transformed consumer smartwatches and wearables into potential clinical tools capable of continuous, real-world rhythm surveillance. This narrative review synthesizes contemporary evidence on smartwatch-based AF monitoring, spanning core technologies—photoplethysmography, single-lead electrocardiography and AI fusion algorithms—and validation studies across post-ablation follow-up. Compared with traditional modalities, smartwatch-based AF monitoring demonstrates improved detection of AF recurrence, enhanced characterization of AF burden, symptom–rhythm correlation, and greater patient engagement. At the same time, key limitations are critically examined, including motion artifacts, false-positive alerts, short recording windows, adherence dependence, digital literacy and access gaps, as well as unresolved issues around regulation, interoperability and data privacy. By integrating engineering advances with guideline-directed care pathways, smartwatch-based AF monitoring holds promise to complement, rather than immediately replace, established diagnostic tools and to enable more proactive, individualized AF management. Future work must focus on robust clinical validation, equitable implementation and clear regulatory frameworks to safely scale these technologies.

It is widely known that various factors contribute to left atrial (LA) mechanical dysfunction in patients with end stage renal disease (ESRD). However, the connection between atrial dysfunction and arrhythmic events such as paroxysmal atrial fibrillation (PAF), in this group of patients, remains unclear. The purpose of our study was to evaluate prospectively the association between LA deformation indices and PAF in ESRD patients. 79 patients (41 men, mean age 57 ± 17) with ESRD and preserved left ventricular systolic function comprised the study population. All patients underwent a baseline comprehensive echocardiography study and were followed for a mean period of 16 ± 5 months. PAF episodes, first and the following events, were reported. LA longitudinal strain reflecting LA reservoir function and LA longitudinal strain rate reflecting LA pump function were specifically evaluated as LA deformation indices of interest, using 2D speckle tracking echocardiography. At the end of follow up period nine patients died. 15 of the rest 70 reported one or more episodes of PAF. LA indexed volumes were significantly higher in patients with PAF (32 ± 26 vs. 21.5 ± 9 ml/m2, p = 0.002), mean LA strain was significantly reduced (17 ± 7 vs. 27 ± 9%, p < 0.001) as well as mean LA stain rate (− 1.19 ± 0.5 vs. − 1.95 ± 0.5 1/s, p < 0.001). Multivariate analysis showed that LA strain rate when adjusted with age together with PAF history remained the single most significant echocardiographic parameter for PAF prediction. Impaired LA strain and LA strain rate are associated with PAF in ESRD patients. LA strain rate might be a better independent predictor of PAF, compared to standard echocardiographic indices. Further prospective studies are needed to validate its relevance in routine clinical practice.