Background: Predicting atrial fibrillation (AF) recurrence remains a major clinical challenge, as conventional echocardiographic parameters often fail to capture the complex electro-mechanical substrate of the arrhythmia. The prognostic significance of right ventricular (RV) function and atrial mechanical–structural coupling in paroxysmal AF (PAF) remains underexplored. Methods: We prospectively enrolled patients with PAF in sinus rhythm undergoing comprehensive echocardiography. A wide range of conventional left-sided, right-sided, and novel coupling indices was assessed. Univariable analysis was performed to screen for potential AF recurrence predictors. Based on the initial findings, receiver operating characteristic (ROC) analysis was used to determine the optimal cutoff for RV fractional area change (RV FAC). Finally, multivariable logistic regression identified independent predictors of AF recurrence over a 12-month follow-up. Results: A total of 73 patients were included, of whom 31 (42.5%) experienced AF recurrence during 12-month follow-up. Conventional left atrial (LA) indices, including LA volume index (LAVI) and reservoir strain, showed no significant association with recurrence. In univariable analysis, RV FAC, LA contraction strain, and the novel LA contraction strain/LAVI ratio were all significant predictors. ROC analysis identified an RV FAC cutoff of 42.5%, with lower values associated with significantly higher recurrence rates. In multivariable analysis, lower RV systolic performance determined by RV FAC ≤ 42.5% emerged as a primary independent predictor of recurrence (p = 0.003), while the LA contraction strain/LAVI ratio demonstrated a strong trend towards significance (p = 0.076). Conclusions: In this exploratory study of patients with PAF, atrial mechanical–structural mismatch emerged as a primary marker of the arrhythmic substrate. Additionally, an exploratory signal suggested that a subclinical reduction in RV performance may also correlate with recurrence, though this warrants further investigation in larger cohorts.

INTRODUCTION:Heart failure with reduced ejection fraction (HFrEF), defined by a left ventricular ejection fraction ≤ 40%, remains a major global health challenge, associated with substantial morbidity, mortality, and impaired quality of life (QoL), particularly in patients with higher NYHA class. Sodium-glucose cotransporter-2 (SGLT2) inhibitors have emerged as a cornerstone therapy for HFrEF, significantly reducing hospitalizations and mortality regardless of glycemic status, sex, race, or comorbidities. METHODS:EVOLUTION-HF was an observational, multi-center, longitudinal cohort study involving 257 consecutive patients diagnosed with HFrEF who initiated dapagliflozin in a routine clinical setting in Greece. The primary objectives were to characterize baseline demographic and clinical features of patients newly initiated on dapagliflozin for HFrEF and to evaluate dapagliflozin treatment patterns, including discontinuation timing, reasons for discontinuation, and concomitant heart failure and glucose-lowering therapies over time. The secondary objectives are to describe patient-reported outcomes using the KCCQ-23 and to assess adherence to dapagliflozin among patients with HFrEF. RESULTS:A total of 257 patients were enrolled and the follow-up period lasted for 12 months. Significant improvements among all KCCQ-23 scores were observed from baseline to 12-months post dapagliflozin initiation, revealing that the initiation and optimization of guideline-directed medical therapy in routine clinical practice provides improvement to quality of life over time. CONCLUSIONS:Dapagliflozin was safe and well-tolerated throughout the observation period. Although benefits are observed in most patients, individuals aged > 65 years, with prior myocardial infarction, or recent hospitalizations show a diminished response, underscoring the need for tailored management and closer follow-up in these higher-risk groups.

Background/Objectives: About one-third of patients who receive cardiac resynchronization therapy (CRT) do not show meaningful clinical improvement. One possible reason is that current criteria for diagnosing left bundle branch block (LBBB) do not clearly separate true conduction block from other conditions that can produce a similar QRS pattern, since they rely mainly on surface ECG features. The Strauss criteria have been proposed as a stricter alternative. They include sex-specific QRS duration thresholds and require a mid-QRS notch or slur, with the goal of better identifying patients whose conduction abnormality may be correctable. Selecting candidates on this basis reflects a personalized-medicine approach that matches resynchronization to the individual conduction substrate rather than applying a single wide-QRS threshold to all patients. In this review, we assess whether LBBB defined by the Strauss criteria is linked to better CRT outcomes, and we examine how these criteria have been used in the design of randomized clinical trials investigating conduction system pacing (CSP). Methods: A systematic search of PubMed, EMBASE, and the Cochrane Library was conducted (last updated April 2026) in accordance with PRISMA 2020 guidelines. Evidence was drawn from two groups of studies: (1) observational studies comparing CRT outcomes in Strauss-positive versus Strauss-negative patients, and (2) randomized CSP trials conducted in populations enriched using either Strauss-type or typical LBBB morphology. Results: A total of 17 comparative studies (n ≈ 4200) were included in Part 1; most (14 of 17) reported outcomes favouring Strauss-defined LBBB, with the greatest signal in non-ischemic cardiomyopathy, although these were mostly small retrospective studies with heterogeneous outcome definitions. However, two large registry analyses found no incremental benefit of strict over conventional criteria. In Part 2, six randomized controlled trials were analyzed. The HeartSync-LBBP trial (n = 200, 36-month follow-up) demonstrated significantly lower rates of mortality or heart failure hospitalization with LBBP compared to BiVP (8% vs. 28%; HR 0.26; 95% CI 0.12-0.57), with 98% technical success for LBBP. In contrast, the PhysioSync-HF trial (n = 173) showed superiority of BiVP, with CSP success of only 69% and 42.8% of procedures performed by less experienced operators. Similarly, the LEFT-BUNDLE-CRT trial (n = 176) found that LBBAP did not meet non-inferiority criteria compared to BiVP (RR 0.95; 95% CI 0.88-1.02). Conclusions: Strauss-defined LBBB is associated with improved CRT outcomes in observational studies, particularly in non-ischemic cardiomyopathy; this reflects an association rather than established superiority or causal benefit, and no randomized trial has yet compared Strauss-guided against guideline-based patient selection. In randomized CSP trials, both operator experience and patient selection appear to be critical determinants of success. BiVP remains effective even in patients meeting strict Strauss criteria. Further research is needed to determine whether the application of Strauss criteria improves outcomes beyond current guideline-based patient selection.

Cardiovascular-kidney-metabolic (CKM) syndrome is a complex clinical entity that encompasses health conditions whose prevalence has markedly increased in recent years, such as atherosclerotic cardiovascular disease, diabetes mellitus, and obesity, which are closely interconnected through shared pathophysiological mechanisms. The need to recognize CKM syndrome arises from its substantial burden on public health, as it is associated with increased morbidity and mortality, particularly in the advanced stages of the disease.Its multifactorial pathophysiology and heterogeneous clinical presentation necessitate a multidisciplinary and holistic approach, including comprehensive diagnostic evaluation and coordinated therapeutic management. involving multiple medical specialties.This expert consensus document, developed under the auspices of the Hellenic Society of Cardiology, represents the first official, national initiative to highlight CKM syndrome as a clinical entity. Its aim is to raise awareness among cardiologists as well as other involved medical specialties, promoting early recognition, appropriate diagnostic approach, and effective therapeutic management of the syndrome.

The right ventricle (RV) is a primary determinant of outcomes in cardiac critical care. RV dysfunction independently predicts morbidity and mortality in conditions such as acute coronary syndromes, pulmonary embolism, and cardiogenic shock. This review synthesizes RV evaluation and management by integrating physiologic principles with bedside diagnostic and therapeutic strategies. The RV is exceptionally sensitive to acute afterload increases due to its adaptation to low-pressure pulmonary circulation. Evaluation utilizes a multimodal approach combining echocardiography, invasive hemodynamics, and specifically the pulmonary artery pulsatility index and central venous pressure/pulmonary capillary wedge pressure (CVP/PCWP) ratio and biomarkers. Management focuses on three pillars: individualized preload optimization, afterload reduction via selective pulmonary vasodilators, and contractility augmentation with inotropes. For refractory cases, mechanical circulatory support options like Impella RP, ProtekDuo, and VA-ECMO provide critical bridges to recovery or transplantation.

BACKGROUND:In CKD, hypertension is often accompanied by sodium sensitivity. Uromodulin promotes sodium sensitivity by activating tubular sodium transporters (NKCC2, NCC). In the general population, individuals with higher urine uromodulin have a positive association between 24-h urine sodium and 24-h BP, whereas those with lower uromodulin show a negative association between these parameters. Whether similar patterns occur in CKD remains unclear. This study evaluated the effect of urine uromodulin on the relationship between 24-h urine sodium excretion and 24-h BP in CKD patients. METHODS:130 patients with CKD G1-G5 on stable antihypertensive treatment underwent 24-h ambulatory BP monitoring and 24-h urine collections. Patients were divided into two groups using the median 24-h urine uromodulin. Associations between 24-h urine sodium excretion and 24-h BP were examined applying multivariable linear regression models. RESULTS:Mean age was 62.6 ± 14.9 years and mean eGFR 49.0 ± 25.1mL/min/1.73m². 24-h SBP, DBP and urine sodium excretion did not differ across CKD stages, whereas urine uromodulin decreased significantly with advancing CKD (p < 0.001). In the multivariable linear regression models of the overall population, neither 24-h urine sodium nor urine uromodulin alone predicted 24-h SBP/DBP. However, in stratified models, higher 24-h urine sodium was associated with higher 24-h SBP (β=0.051, 95%CI:0.018-0.087, p = 0.005) and DBP (β=0.041, 95%CI:0.018-0.068, p = 0.002) only in the high-uromodulin group. In contrast, in the low-uromodulin group, no significant associations were observed. The β-coefficients for urine sodium differed significantly between uromodulin groups for both 24-h SBP and DBP models (p = 0.025 and p = 0.004 respectively). CONCLUSIONS:In CKD, urine uromodulin modifies the association between dietary sodium intake and ambulatory BP. Patients with higher urine uromodulin show a positive association between 24-h sodium excretion and BP, whereas this finding is absent in those with lower uromodulin. These findings support urine uromodulin as a useful biomarker of sodium sensitivity in CKD. CLINICAL TRIAL REGISTRATION NUMBER:NCT06363097 (ClinicalTrial.gov).

BACKGROUND:Myocardial infarction with non-obstructive coronary arteries (MINOCA) is a heterogeneous condition with variable outcomes. The prognostic value of common clinical risk factors for major adverse cardiac events (MACEs) and all-cause mortality remains unclear. This study systematically evaluates associations between traditional risk factors and adverse outcomes in MINOCA. METHODS:A systematic review and meta-analysis was conducted to assess pooled hazard ratios (HRs) for clinical variables associated with MACEs and all-cause mortality. Eligible studies reporting HRs with at least 6 months of follow-up were included. Random-effects models were used to derive pooled estimates. RESULTS:Eleven studies including 12,081 patients were analyzed. Over a mean follow-up of 49.2 months, pooled MACEs incidence was 17% (95% CI: 11-26%) and all-cause mortality was 10% (95% CI: 8-14%). Older age increased the risk of MACEs (HR: 1.02; 95% CI: 1.01-1.04), while higher BMI was protective (HR: 0.92; 95% CI: 0.86-0.99). For all-cause mortality, significant predictors included age (HR: 1.04 per year), diabetes (HR: 1.33; 95% CI: 1.07-1.64), creatinine (HR: 1.01; 95% CI: 1.0009-1.02), and STEMI-pattern presentation (HR: 2.85; 95% CI: 1.09-7.44). Higher BMI (HR: 0.89; 95% CI: 0.82-0.98) and dyslipidemia (HR: 0.83; 95% CI: 0.76-0.90) were associated with lower mortality. CONCLUSION:Only select clinical variables predict outcomes in MINOCA, while many traditional MI risk factors do not. These findings highlight the need for MINOCA-specific risk models and targeted management strategies.

INTRODUCTION:Radiotherapy for breast cancer has a clear benefit for long-term survival and local control rate. However, it can negatively impact a patient's quality of life by affecting healthy surrounding normal tissues, including the heart and lungs. This study aimed to clarify the contribution of echocardiography with Global Longitudinal Strain (GLS) to early radiation-induced cardiotoxicity detection. METHODS:A prospective study was conducted on 25 early-stage left-sided breast cancer patients. All underwent 2D strain echocardiography before and one year after RT. Normality was assessed using the Shapiro-Wilk test and box plots. The Wilcoxon signed-rank test was conducted to compare GLS values. A statistical analysis was performed using Statistical Package for the Social Sciences (SPSS) version 25. RESULTS:Mean Global Longitudinal Strain value before and one year after radiotherapy was -20.2% and -21.2%, respectively. In half of these cases, the values ranged from -19.65% to -22.70% before radiotherapy and between -18.8% and -22.25% after radiotherapy. The non-parametric Wilcoxon test indicated no statistically significant difference before and after radiotherapy (Ζ = 0.902, p = 0.367). DISCUSSION:Although no statistically significant reduction in GLS was observed one year post-radiotherapy, a decrease was noted in patients receiving higher cardiac doses, suggesting potential early subclinical myocardial changes. Strain echocardiography shows promise as a sensitive tool for the early detection of radiation-induced cardiotoxicity, warranting further research with larger cohorts and extended follow-up. CONCLUSION:While this small cohort study did not show significant GLS changes post-RT, it highlights the need for larger studies with longer follow-ups to confirm the role of strain imaging in identifying early cardiotoxicity in breast cancer patients.

BACKGROUND:Left bundle branch block (LBBB) is a well-established predictor of response to cardiac resynchronization therapy (CRT) in heart failure with reduced ejection fraction. However, several electrocardiographic definitions are used, and their relative significance remains unclear. HYPOTHESIS:Stricter electrocardiographic definitions of LBBB are associated with improved response to CRT and more favorable clinical outcomes. METHODS:We conducted a retrospective single-center cohort study including 109 patients who underwent CRT-defibrillator implantation. Baseline electrocardiograms were classified according to six commonly used LBBB definitions. The primary endpoint was echocardiographic response at 6 months, defined as a ≥ 10% absolute increase in left ventricular ejection fraction or a ≥ 15% reduction in left ventricular end-systolic volume. Secondary endpoints included heart failure hospitalization and all-cause mortality. Multivariable logistic, Cox, and negative binomial regression models were used, with odds ratios (OR), hazard ratios (HR), incidence rate ratios (IRR), and 95% confidence intervals (CI). RESULTS:Strauss-defined LBBB was independently associated with echocardiographic response (adjusted OR, 7.47; 95% CI, 2.52-25.0; p < 0.001) and showed the highest discriminative performance (area under the curve, 0.728; 95% CI, 0.643-0.814). Strauss was also associated with lower heart failure hospitalization rates (adjusted IRR, 0.30; 95% CI, 0.13-0.64; p = 0.002) and reduced mortality (adjusted HR, 0.14; 95% CI, 0.02-0.99; p = 0.049). Median follow-up was 30 months (IQR 14-60). CONCLUSIONS:Different LBBB definitions are associated with differences in CRT response and outcomes. Stricter criteria appear to better identify patients more likely to respond, with more favorable outcomes. These findings may help refine patient selection for CRT.

Background/Objectives: Systemic and tissue inflammation play a crucial role in the pathophysiology of cardiometabolic disorders. Presepsin is a newly discovered marker of acute phase inflammation that is produced by monocytes or macrophages in response to bacterial infection and is a soluble fraction of the lipopolysaccharide (LPS) receptor. LPS is an endotoxin that, through the breakdown of the intestinal barrier, penetrates the systemic circulation and is an important bacterial mediator in the pathogenesis of sepsis and septic shock. Methods: A narrative review of the existing literature. Results: A growing body of evidence demonstrates that intestinal dysbiosis is involved in the pathogenesis of diabetes mellitus (DM) and cardiovascular (CV) disease, leading to increased circulating LPS concentrations in people with cardiometabolic disorders, even in the absence of infection. These data provide the theoretical background for a link between presepsin, DM, and CV pathology. Preliminary studies suggest that presepsin levels are downregulated in patients with well-controlled type 2 DM and correlate with continuous glucose monitoring metrics in infection-free individuals with type 1 DM. However, prospective data on the association between presepsin and the risk of diabetic complications are currently lacking. Presepsin has also been found to be elevated in infection-free individuals with myocardial infarction, heart failure, and myocarditis compared to controls and has been shown to correlate with mortality risk in subjects at high CV risk. Conclusions: The clinical utility of presepsin in the monitoring of patients with cardiometabolic disorders warrants further investigation by future studies.

Background: Short QT syndrome (SQTS) is a rare inheritable channelopathy characterized by a shortened corrected QT interval on an electrocardiogram and a significant risk of atrial and ventricular arrhythmias, potentially leading to sudden cardiac death. Despite advancements in our understanding of SQTS, knowledge gaps persist due to its extreme rarity. This scoping review aims to summarize the available knowledge on its clinical presentations, genetic mutations, and management strategies, while identifying areas for further investigation. Methods: This scoping review was conducted across the PubMed, Scopus, and Cochrane databases and identified relevant case reports, case series, and available studies on SQTS. We focused on articles that reported clinical outcomes, genetic mutations, diagnostic criteria, and management strategies, while excluding studies on the secondary causes of short QT intervals. Results: SQTS is present across a wide age range, from asymptomatic individuals to those experiencing syncope, palpitations, or sudden cardiac arrest. Common genetic mutations include KCNQ1, KCNH2, and KCNJ2. Management strategies vary, with some patients receiving implantable cardioverter defibrillators for secondary prevention and others treated pharmacologically, primarily with hydroquinidine. Our findings highlight the rarity and clinical variability of SQTS, underscoring the need for optimized diagnostic criteria and individualized management strategies. Conclusions: This review emphasizes the need for continued research to better understand the genetic basis of SQTS, optimize diagnostic tools, and improve treatment approaches. Large-scale studies and the integration of genetic and clinical data are critical to addressing the gaps in SQTS management and improving outcomes for patients with this potentially life-threatening arrhythmic disorder.

Heart failure with preserved ejection fraction (HFpEF) remains a major clinical challenge due to its heterogeneous presentation and limited therapeutic options. Accurate patient phenotyping is essential to improve diagnosis, prognostication, and treatment personalization. Machine learning (ML) has emerged as a powerful tool to identify clinically meaningful HFpEF subgroups by integrating diverse data sources, including clinical, imaging, biomarker, and physiological parameters. ML-based models can uncover subtle patterns not captured by traditional methods, offering improved risk stratification, earlier intervention, and guidance toward individualized therapy. Future progress will rely on standardized data collection, validation across populations, and incorporation into clinical decision support systems. Advancements in explainable artificial intelligence, federated learning, and multi-omics integration are expected to further refine phenotyping strategies and translate into improved patient outcomes. Continued interdisciplinary collaboration is essential to unlock the full potential of ML in transforming HFpEF management.

Background: Paroxysmal atrial fibrillation (PAF) presents significant challenges in management due to its unpredictable recurrence and associated complications. Current prognostic tools lack precision in predicting PAF outcomes, highlighting the need for a comprehensive approach integrating multiple diagnostic modalities. Methods: The PLACEBO pilot study is a prospective observational investigation enrolling 80 adults with PAF from a tertiary hospital. Baseline assessments include cardiopulmonary exercise testing (CPET), a complete echocardiographic evaluation, 24-h ambulatory electrocardiographic monitoring, and plasma biomarker analysis. Participants will be followed for 12 months, with the primary outcome being AF recurrence. Secondary outcomes include cardiovascular events and other clinical indicators relevant to disease progression. Results: The study will assess the feasibility of integrating CPET parameters, echocardiographic indices, and plasma biomarkers into clinical practice for prognostic evaluation. Data analysis will focus on identifying potential associations between these modalities and PAF recurrence, contributing to improved risk stratification. Conclusions: By integrating CPET, echocardiographic parameters, and plasma biomarkers, the PLACEBO pilot study aims to enhance risk stratification and improve the prognostic assessment of patients with PAF. The findings from this study may pave the way for future research, ultimately contributing to the development of personalized management strategies.

Background: Atrial fibrillation is a prevalent arrhythmia with significant morbidity and recurrence challenges. Paroxysmal atrial fibrillation (PAF) is characterized by episodic occurrences and unpredictable recurrences; therefore, it demands innovative diagnostic approaches to predict relapses and guide management. Objectives: This pilot, exploratory study evaluates the feasibility and prognostic value of integrating cardiopulmonary exercise testing (CPET), echocardiographic indices, and plasma biomarkers for predicting PAF recurrence. Methods: The PLACEBO trial is a single-center, prospective observational study of 73 adults with PAF in sinus rhythm at baseline. Comprehensive assessments included CPET, transthoracic echocardiography, 24 h electrocardiographic Holter monitoring with heart rate variability (HRV) metrics, and plasma biomarkers, such as galectin-3 (GAL3). Recurrence was defined as any documented AF episode lasting ≥30 s within 12 months of follow-up. Results: Binary logistic regression revealed that the standard deviation of RR intervals (SDRR) and GAL3 were significant predictors of recurrence. Particularly, higher SDRR [odds ratio (OR): 1.061, p = 0.021] and GAL3 > 10.95 ng/mL (OR: 5.206, p = 0.006) were associated with recurrence. Moreover, lower right ventricular fractional area change (RV FAC) exhibited a marginally significant association with recurrence (OR: 0.927, p = 0.062). CPET parameters demonstrated limited prognostic value in this cohort. Conclusion: This pilot study demonstrates that integrating novel echocardiographic indices, biomarkers, and HRV metrics is feasible and may provide valuable prognostic insights for PAF recurrence. Larger multicenter studies are needed to validate these findings and optimize personalized risk stratification strategies.

Mitral annular disjunction (MAD) is an increasingly recognized structural abnormality of the mitral valve apparatus, often associated with mitral valve prolapse and a heightened risk of ventricular arrhythmias and sudden cardiac death. It is defined by a separation between the mitral annulus and the left ventricular myocardium, best visualized during systole. In this review, we present an updated and comprehensive overview of MAD, drawing from recent large-scale imaging studies, expert consensus documents, and newly proposed classifications such as true versus pseudo-MAD. We discuss its prevalence, anatomical features, and diagnostic challenges across multiple imaging modalities, including transthoracic and transesophageal echocardiography, cardiovascular magnetic resonance, and computed tomography. We also explore its pathophysiological role in arrhythmogenesis, its prognostic implications, and current management strategies. Special attention is given to risk stratification based on imaging and cardiac rhythm findings, and we propose a practical clinical framework to guide decision-making. This review aims to support clinicians in recognizing MAD as a potentially arrhythmogenic condition that requires systematic evaluation and follow-up.