The association between cardiovascular (CV) pathologies and metabolic/endocrine dysfunctions was first observed a long time ago, and great emphasis has been given to this relationship [...]

Background: The relationship between physical exercise and human longevity constitutes one of the most consequential intersections in contemporary preventive medicine. Although international guidelines recommend 150 min of moderate-intensity exercise weekly, growing evidence suggests that the architecture of optimal exercise is far more complex, encompassing dose, modality, timing across the lifespan, and the paradox risks imposed by extreme endurance. Methods: We included in this narrative review landmark cohort studies, randomized controlled trials, meta-analyses, and expert physiological frameworks published in high-impact cardiovascular, sports medicine, and longevity journals from 1966 to 2024. Results: Cardiorespiratory fitness (CRF), indexed by maximal oxygen uptake (VO2 max), demonstrates the strongest and most linear dose-response relationship with all-cause mortality identified in preventive medicine, with every 1 metabolic equivalent of task (MET) increment associated with a 12-15% reduction in mortality risk. The optimal dose of vigorous-intensity exercise follows a J-shaped dose-response curve: 3-5 sessions per week generating 1-2.4 h of vigorous activity is associated with the lowest all-cause mortality risk in large prospective cohorts, whereas chronic extreme endurance exercise incurs measurable atrial remodeling, patchy myocardial fibrosis, and a 5.3-fold increase in the risk of atrial fibrillation. The importance of exercise types shifts profoundly across the lifespan, transitioning from aerobic capacity effort in the third decade to resistance training in the seventh decade and neuromuscular stability in the eighth. Based on our interpretation of the available evidence, we propose a structured, personalized four-step exercise pathway integrating CRF assessment, lifespan-adapted prescription, lifestyle co-interventions, and periodic reassessment. Conclusions: Among currently available lifestyle interventions, regular exercise is consistently associated with some of the largest and most reproducible reductions in all-cause and cardiovascular mortality observed in prospective cohort data, while remaining accessible and cost-effective.

Cardiovascular imaging is a cornerstone of modern cardiology, yet its clinical impact is limited by operator dependence, inter-observer variability, time-consuming workflows, and unequal access to advanced expertise. Artificial intelligence (AI), particularly machine learning and deep learning, offers new opportunities to overcome these limitations. This review aims to summarize current and emerging AI applications in cardiovascular imaging and to evaluate their potential clinical value in precision diagnostics and decision support. This narrative review synthesizes clinically relevant literature on AI applications across major cardiovascular imaging modalities, including echocardiography, cardiovascular magnetic resonance, cardiac computed tomography, and nuclear cardiology. Evidence was analyzed with a focus on AI-enabled acquisition support, image segmentation, quantitative and functional assessment, workflow automation, and risk stratification, alongside key methodological and implementation considerations. Across imaging modalities, AI-driven approaches have demonstrated improved reproducibility, efficiency, and scalability of cardiovascular imaging workflows. Automated algorithms reduce operator dependence, facilitate standardized extraction of imaging biomarkers, and support advanced functional assessment and prognostic stratification. Recent developments in video-based, temporal, and multimodal models further expand AI capabilities from technical automation toward integrated disease phenotyping and personalized clinical decision support. However, translation into routine practice remains limited by heterogeneous datasets, insufficient external validation, algorithmic bias, limited interpretability, and challenges related to regulatory approval and workflow integration. Artificial intelligence has the potential to reshape cardiovascular imaging into a more efficient, reproducible, and patient-centered precision medicine tool. Real-world clinical impact will depend on outcome-driven evaluation, robust external validation, multimodal data integration, and human-in-the-loop implementation strategies that ensure safe, equitable, and clinically meaningful adoption.

A key limitation in contemporary HF management is the marked heterogeneity of the syndrome, driven by diverse pathophysiological mechanisms that are not fully captured by traditional classifications based on left ventricular ejection fraction. Precision medicine has emerged as a promising approach to address this heterogeneity by integrating clinical characteristics, circulating biomarkers, advanced imaging, and computational phenotyping strategies. However, current frameworks predominantly emphasize myocardial dysfunction, while the contribution of vascular abnormalities remains underrepresented. The interaction between the left ventricle and the arterial system plays a fundamental role in cardiovascular performance. Arterial stiffness, commonly assessed by pulse wave velocity (PWV), represents a key determinant of vascular aging and a robust predictor of cardiovascular risk. Increasing evidence suggests that vascular dysfunction contributes significantly to the pathophysiology and clinical expression of HF, particularly in phenotypes characterized by preserved ejection fraction. This review synthesizes current evidence on precision medicine in HF and highlights the emerging role of arterial stiffness and PWV in multidimensional patient phenotyping. We propose that integrating vascular parameters into existing phenotyping frameworks may enhance risk stratification, improve mechanistic understanding, and support the development of more personalized therapeutic strategies in heart failure. Unlike previous reviews that have addressed arterial stiffness or heart failure phenotyping separately, this work uniquely integrates ventricular-vascular interaction and pulse wave velocity into a comprehensive precision medicine framework for heart failure. By bridging vascular physiology with data-driven phenotyping strategies, this review provides a novel conceptual model for incorporating arterial stiffness into multidimensional patient characterization across the full spectrum of heart failure phenotypes.

Familial hypercholesterolemia (FH) and familial hypertriglyceridemia (FHTG) represent a spectrum of inherited conditions with profoundly different etiologies, risk profiles, and therapeutic implications. Despite decades of clinical experience, their formal diagnostic definitions remain rooted in frameworks developed before the genomic era (the Dutch Lipid Clinic Network (DLCN) score), leading to substantial gaps in diagnostic accuracy. This review traces the historical evolution of diagnostic criteria for FH and FHTG from early phenotypic observation to contemporary genomic and biomarker-driven models. It systematically evaluates the major limitations of current criteria, including the (DLCN) score, and integrates evidence from landmark Mendelian randomization (MR) studies to identify persistent gaps. A narrative synthesis of landmark clinical, epidemiological, and genetic studies was performed, encompassing the original discovery of the low-density lipoprotein cholesterol (LDL-C) receptor pathway, the development of international diagnostic criteria, and contemporary mendelian randomization (MR) evidence on the causal roles of LDL-C, lipoprotein (a) [Lp(a)], triglyceride-rich lipoprotein remnants, and apolipoprotein B (ApoB). Current diagnostic frameworks suffer from age-dependent confounding of LDL-C measurements, failure to account for Lp(a)-mediated phenocopies, inadequate discrimination between monogenic and polygenic etiologies, sex differences, ethnicity, and inapplicability to pediatric populations. MR data reveal that the causal architecture of cardiovascular risk in these disorders is particle-centric (ApoB) rather than LDL-C-centric, and that remnant cholesterol, not triglyceride per se, drives atherosclerotic cardiovascular disease risk in FHTG. We evidenced the evolution of treatment options and the morbidity and mortality rates for FH and FHTG from the 1970s until the 2020s. Future diagnostic paradigms should integrate lifetime Lp(a) measurement, polygenic risk scoring, ApoB quantification, and cascade genomic testing to replace phenotype-only approaches. This review concludes by proposing a four-step integrated diagnostic algorithm for FH and FHTG.

Mechanical complications after acute myocardial infarction (MI)—ventricular septal rupture (VSR), free-wall rupture (FWR), and papillary muscle rupture (PMR)—have become uncommon in the primary percutaneous coronary intervention (PCI) era, yet remain among the most lethal cardiovascular emergencies, with contemporary mortality largely driven by cardiogenic shock and delays to definitive treatment. Although major society documents agree on urgent imaging, early mechanical circulatory support when shock is present, and multidisciplinary decision-making, important transatlantic differences persist, particularly regarding timing of intervention in ventricular septal rupture. This review synthesises current surgical and transcatheter evidence and proposes a unified, physiology-centred framework integrating shock staging, anatomical feasibility, and response to mechanical support. We also introduce STABLE, a structured bedside checklist designed to support consistent daily triage across all three lesions and to align timing decisions with haemodynamic stabilisation rather than centre-specific habit.

Background/Objectives: Heart failure (HF) in patients with conventional right ventricular pacing with significant pacing percentages is still a subject of concern, and management of HF in this population has historically been difficult; however, novel HF pillar medications, such as SGLT2 inhibitors (SGLT2i) and angiotensin receptor/neprilysin inhibitors (ARNi), have fundamentally transformed contemporary pharmacological HF management. The aim of this study was to assess left ventricular (LV) function after current guideline-directed medical therapy (GDMT) in patients with chronic right ventricular (RV) pacing and HF. Methods: Patients with a lifetime ventricular pacing percentage > 20% (Vp > 20%) and HF diagnosed according to ESC guideline criteria were included. Device interrogation and transthoracic echocardiography (TTE), including assessment of left ventricular ejection fraction (LVEF) and mitral annular plane systolic excursion (MAPSE), were performed at GDMT initiation and during subsequent follow-up. Changes in LVEF and MAPSE were assessed overall and according to baseline HF phenotype. Multivariable linear regression analyses were performed to identify independent predictors of changes in LVEF and MAPSE. Results: Among 550 conventionally paced patients screened for HF, 127 (23.1%) met the inclusion criteria and underwent GDMT initiation. Mean age was 68.2 ± 12.1 years, and mean follow-up duration was 10.2 ± 6.3 months. Baseline LVEF and MAPSE were 48.7 ± 6.3% and 12.0 ± 2.4 mm, respectively. All patients received SGLT2i therapy, while 24 (18.9%) received ARNi. Overall, LVEF increased by 1.94 ± 2.47% and MAPSE by 0.84 ± 0.96 mm (both p < 0.001). Patients with HFrEF (n = 25) showed an increase in LVEF of 5.84 ± 2.53% and MAPSE of 1.72 ± 1.21 mm. In patients with HFmrEF, LVEF increased by 2.50 ± 1.54% and MAPSE by 0.83 ± 0.92 mm, whereas in HFpEF, LVEF increased by 0.67 ± 0.78% and MAPSE by 0.58 ± 0.71 mm. NYHA functional class improved by at least one class in 100 patients (78.7%). In multivariable analysis, ARNi use was independently associated with greater improvement in LVEF and MAPSE, while lower baseline LV function was associated with greater subsequent improvement. Conclusions: In patients with HF and chronic RV pacing, GDMT was associated with modest but statistically significant improvements in LV systolic function, assessed by LVEF and MAPSE, across the HF spectrum. The greatest improvements were observed in patients with HFrEF. However, given the observational design, absence of a control group, and universal use of SGLT2i, these findings do not establish a causal treatment effect or demonstrate superiority of any specific GDMT combination. Prospective controlled studies are warranted to determine the clinical significance of these changes and the independent contribution of individual therapies.

Background: The Heart Rate Recovery Index (HRRI), derived from post-exercise heart rate recovery (HRR), reflects autonomic function and cardiovascular performance. Whether HRRI reflects early myocardial dysfunction and left atrial remodelling in heart failure with preserved ejection fraction (HFpEF) has not been previously examined. The H2FPEF score, which integrates clinical and echocardiographic parameters, is used to assess the likelihood of HFpEF. This study investigates the relationship between HRRI, H2FPEF score, and echocardiographic markers of longitudinal systolic function, including mitral annular plane systolic excursion (MAPSE), as well as left atrial volume index (LAVI), in patients with preserved left ventricular ejection fraction. Methods: A prospective observational study included 241 patients referred for cardiac exercise testing at the Institute of Cardiovascular Diseases Timisoara and the Clinical County Hospital of Sibiu. HRRI was calculated as the ratio of heart rate acceleration time (AT) to deceleration time (DT) during exercise testing. A comprehensive echocardiographic assessment was performed on all patients. Statistical analysis involved univariate testing and multivariable logistic regression with stepwise selection. Results: HRRI was significantly lower in HFpEF patients compared with those without heart failure (1.97 ± 0.66 vs. 2.73 ± 1.08, p < 0.01). HRRI correlated significantly with exercise performance, age, H2FPEF score, and echocardiographic markers of diastolic and longitudinal systolic dysfunction. ROC analysis identified an HRRI cut-off value of 2.25 for HFpEF detection (AUC = 0.748), while HRRI remained significantly associated with HFpEF after adjustment for the covariates included in the model. The combined HRRI–H2FPEF score improved diagnostic discrimination compared with the H2FPEF score alone (AUC 0.897 vs. 0.858), achieving an overall classification accuracy of 82.2%. Conclusions: In our study, HRRI is significantly reduced in HFpEF and distinguishes patients with and without heart failure. It shows associations with echocardiographic markers of diastolic and longitudinal systolic dysfunction, exercise capacity, and H2FPEF score.

Background/Objectives: Cardiac resynchronization therapy (CRT) is a cornerstone treatment for heart failure with reduced ejection fraction (HFrEF), yet many patients remain symptomatic despite long-term electrical optimization. Although sacubitril/valsartan (ARNI) is central to guideline-directed medical therapy (GDMT), data on its late initiation in patients with chronic CRT are scarce. This study evaluated the impact of delayed ARNI initiation on clinical status, functional capacity, and cardiac remodelling in a real-world CRT population. Methods: We performed a single-centre, retrospective observational study including 76 HFrEF patients with chronic CRT who started ARNI between 2022 and late 2024. Patients underwent standardized assessment at baseline (T0) and after 12 ± 3 months (T1), including clinical evaluation, 12-item Kansas City Cardiomyopathy Questionnaire (KCCQ-12), symptom-limited bicycle exercise testing, and comprehensive echocardiography. The primary endpoint was change in quality of life (QoL). Secondary endpoints included exercise capacity, echocardiographic reverse remodelling, NYHA class, loop diuretic dose, and device-detected arrhythmias. Dose-response and multidimensional response patterns were explored. Results: KCCQ-12 increased from 52.96 ± 16.33 to 75.55 ± 18.12 (Δ +22.59 ± 13.22, p < 0.001), with 89.5% achieving a clinically meaningful improvement. Exercise duration and peak workload improved significantly. LVEF increased from 35.08 ± 6.96% to 43.18 ± 8.42% (Δ +8.11%, p < 0.001), with reductions in left ventricular and atrial volumes. Loop diuretic dose decreased (median -10 mg/day furosemide equivalent, p < 0.001), and 26.3% discontinued diuretics. A lower prevalence of device-detected arrhythmias was observed at follow-up, from 34.2% to 6.6% (p < 0.001). Higher ARNI doses were associated with greater likelihood of clinical, functional, and structural response. Longer CRT duration reduced the probability of structural remodelling but not symptomatic or functional benefit. Conclusions: In patients with long-standing CRT, delayed ARNI initiation was associated with improvements in QoL, exercise capacity, cardiac remodelling, congestion status, and electrical stability. These findings suggest that CRT is not a therapeutic ceiling and that late ARNI initiation remains a valuable component of comprehensive GDMT.

Background: Sacubitril/valsartan is a cornerstone of guideline-directed medical therapy for heart failure with reduced ejection fraction (HFrEF), yet data regarding reverse remodeling after ARNI initiation in patients previously treated with cardiac resynchronization therapy (CRT) remain limited. This study evaluated echocardiographic reverse remodeling following sacubitril/valsartan initiation in a real-world cohort of CRT-treated patients and explored the association between treatment timing and remodeling response. Methods: This single-center retrospective pilot study included 188 patients with HFrEF treated with CRT who subsequently initiated sacubitril/valsartan. Patients were categorized into early (≤12 months after CRT, n = 112) and late (>12 months, n = 76) initiation groups. Echocardiographic parameters and functional status were assessed at baseline and at approximately 12 months. Reverse remodeling was evaluated using changes in left ventricular ejection fraction (LVEF), ventricular volumes, and clinical status. Multivariable logistic regression was used to explore factors associated with reverse remodeling (ΔLVEF ≥ 10%). Results: Sacubitril/valsartan therapy was associated with significant improvements in LVEF, left ventricular end-diastolic volume, left atrial volume, and NYHA functional class in both groups. The magnitude of improvement in echocardiographic parameters was similar between early and late initiation groups. In exploratory multivariable analyses, earlier ARNI initiation was associated with clinically meaningful reverse remodeling (ΔLVEF ≥ 10%) (OR 6.36, 95% CI 1.59–25.50, p = 0.009). SGLT2 inhibitor therapy was also associated with reverse remodeling (OR 5.76, 95% CI 1.86–17.87, p = 0.002), while a longer CRT-to-ARNI interval was associated with lower odds of response (OR 0.77 per year, 95% CI 0.62–0.96, p = 0.018). Analysis of CRT-to-ARNI interval as a continuous variable showed only a weak association with reverse remodeling, while receiver operating characteristic analysis did not identify a meaningful temporal threshold (AUC 0.497). Conclusions: Sacubitril/valsartan initiation after CRT was associated with significant reverse remodeling, including in patients who initiated therapy several years after CRT implantation, although the late-initiation subgroup was of limited size, and treatment intervals beyond the interquartile range (4.0–7.0 years) were sparsely represented. Absolute echocardiographic improvements were broadly similar between groups, and receiver operating characteristic analysis did not identify a discriminative temporal threshold (AUC 0.497), indicating no discriminative ability beyond chance. Exploratory multivariable analysis identified an association between earlier initiation and clinically meaningful reverse remodeling, but this finding was not supported by a clinically meaningful temporal threshold.

Background and Objectives: Cardiovascular disease remains the leading cause of premature mortality worldwide. Subclinical glucose dysregulation, a contributor to accelerated vascular aging, is undetectable by conventional screening in apparently healthy individuals; even within the normal glycemic range, postprandial glucose excursions promote endothelial injury and inflammatory pathways independently of mean glucose levels. Hypothesis: Continuous glucose monitoring (CGM)-guided metabolic phenotyping, combined with personalized dietary optimization, structured fasting protocols, and selective longevity-oriented pharmacotherapy, constitutes a mechanistically coherent, hypothesis-generating preventive strategy that may attenuate cardiovascular risk and biological aging in apparently healthy non-diabetic adults, pending confirmation in prospective outcome trials. Materials and Methods: This narrative review synthesizes evidence from prospective cohort studies, randomized controlled trials, and mechanistic investigations connecting CGM-guided metabolic assessment with preventive cardiology and the emerging field of longevity medicine, focusing on glycemic variability biology, nutrient-sensing pathways, and the cardiovascular and longevity profiles of low-dose metformin and acarbose. Results: CGM-derived metrics capture inter-individual glycemic variability invisible to standard assessments and provide behavioral feedback for dietary personalization. Structured fasting and low-dose metformin converge on shared nutrient-sensing pathways implicated in both vascular aging and longevity, with CGM enabling objective confirmation of metabolic adaptation. Acarbose has shown cardiovascular and lifespan benefit signals in secondary trial analyses and preclinical longevity models, though these findings require replication and are not yet established in non-diabetic populations. Conclusions: We propose a four-phase research framework integrating CGM metabolic phenotyping, dietary optimization, fasting titration, and selective pharmacological augmentation for apparently healthy adults at cardiovascular risk. Prospective hard-endpoint trials are lacking, and this framework should be regarded as hypothesis-generating rather than an established clinical strategy, warranting rigorous outcome-based evaluation before clinical adoption.

Background: Postprandial triglyceride (TG) metabolism represents a dynamic dimension of lipid physiology that complements conventional fasting lipid assessment. Although low-density lipoprotein cholesterol (LDL-C) remains the primary therapeutic target in cardiovascular prevention, residual cardiovascular risk persists in many individuals despite apparently adequate fasting lipid control. Because most individuals spend the majority of their waking hours in a fed state, postprandial TG responses may provide clinically relevant insight into metabolic flexibility, dietary exposure, and the efficiency of TG-rich lipoprotein clearance. Methods: This narrative review was conducted using a literature search guided by predefined themes, keywords, and databases, without following a formal systematic review protocol. Randomized controlled trials, observational studies, meta-analyses, and major reviews addressing postprandial lipid metabolism, dietary determinants, and cardiometabolic risk were included, with priority given to human studies. Results: Postprandial TG responses are strongly influenced by dietary composition, eating patterns, and metabolic health. Individuals with insulin resistance, type 2 diabetes, obesity, and metabolic-associated steatotic liver disease (MASLD) frequently demonstrate exaggerated or prolonged postprandial lipemia even when fasting TG concentrations appear acceptable. While circulating TGs serve as practical clinical markers of postprandial lipid handling, cholesterol-enriched remnant lipoproteins more closely reflect atherogenic burden. Nutritional interventions, weight management, and physical activity consistently improve postprandial TG dynamics, whereas pharmacologic therapy provides additional benefit in selected high-risk patients. Non-fasting TG measurements may provide additional insight into postprandial lipid metabolism and residual cardiovascular risk, although standardized protocols and validated clinical thresholds remain to be established. Conclusions: Postprandial TG metabolism provides clinically meaningful information beyond fasting lipid measurements and represents a useful adjunct for refining residual cardiovascular risk assessment. Although standardized protocols remain limited, integrating nutritional and clinical perspectives may support a more comprehensive and individualized approach to cardiometabolic prevention.

Background: Atrial fibrillation (AF) is associated with atrial remodelling, hemodynamic stress, and complex cardiopulmonary interactions. While natriuretic peptides and echocardiographic abnormalities are established markers of AF-related substrate, the contribution of spirometry changes, as a landmark of pulmonary impairment, remains less clearly defined. This study evaluated whether AF is associated with an integrated cardiopulmonary profile characterized by altered spirometry, increased NT-proBNP, and conventional echocardiographic markers of left atrial structure and function. Methods: We performed a retrospective, single-center observational study based on an existing clinical database of adult patients referred for 24 h 12-lead Holter ECG monitoring because of palpitations and/or chest pain. None of the included patients had a previously documented diagnosis of atrial fibrillation before Holter monitoring. Because a single 24 h Holter recording cannot establish spontaneous termination or long-term temporal pattern with certainty, AF documented for the first time during this recording is referred to throughout as “newly detected AF” rather than “paroxysmal AF”. During Holter monitoring, no ECG changes suggestive of myocardial ischemia were detected. From 536 records of patients without previously known AF who underwent 24 h 12-lead Holter ECG monitoring for palpitations and/or chest pain, 164 patients were retained for the main comparison, including 48 with newly detected paroxysmal AF and 116 without AF. Demographic, biochemical, spirometric, and echocardiographic variables were analyzed. The main respiratory parameters were forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), and peak expiratory flow (PEF). NT-proBNP was the primary biomarker, while conventional left atrial structural and functional variables were used for echocardiographic assessment. Results: NT-proBNP was markedly higher in the AF group (684.5 vs. 62.3 pg/mL, p = 0.001), even when accounting for confounders like age, CKD, or CPD, showing by far the largest between-group difference among the biomarkers assessed (formal discrimination statistics such as ROC/AUC were not computed). The exploratory inflammatory markers assessed (hs-CRP, neutrophil/lymphocyte ratio, homocysteine) showed only modest, non-significant differences. Conventional echocardiographic parameters did not differ significantly between groups. In the strict complete-case comparison, spirometric indices did not reach statistical significance; however, preliminary project-level analysis showed lower FVC, FEV1, and PEF in AF patients, but without supporting the COPD diagnosis, and exploratory correlations suggested a relationship between spirometric performance and left atrial function. Conclusions: In this cohort, AF was most strongly associated with NT-proBNP, while the respiratory signal was weaker but directionally consistent with a broader cardiopulmonary phenotype. These findings do not support spirometry or NT-proBNP as stand-alone diagnostic tools for AF. However, when interpreted alongside traditional AF risk factors and symptoms, elevated NT-proBNP with concordant spirometric impairment may represent a hypothesis-generating additive signal supporting longer or repeated rhythm monitoring beyond 24 h in selected patients with suspected AF; this additive value was not formally tested against clinical models alone and requires prospective confirmation.

Background/Objectives: Cardiac resynchronization therapy (CRT) and angiotensin receptor–neprilysin inhibitors (ARNIs) are cornerstone therapies for patients with heart failure with reduced ejection fraction (HFrEF). However, nearly 30% of patients show no significant response to CRT alone. The potential of ARNI to enhance CRT outcomes—especially in non-responders—is an emerging field of interest. The objective of this review is to systematically evaluate and synthesize the available evidence on the clinical outcomes of combining CRT with ARNI therapy in patients with HFrEF. Methods: We conducted a comprehensive search of PubMed, Scopus, and Google Scholar up to September 2024, using the keywords “CRT and ARNI” and “cardiac resynchronization therapy and sacubitril/valsartan”. We included retrospective and prospective clinical studies, observational studies, and review articles reporting on patients with HFrEF treated with both CRT and ARNI. Studies not in English, animal studies, and those without full-text availability were excluded. Study selection and data extraction were performed in duplicate by independent reviewers, using PRISMA guidelines for transparency. The final selection included 8 studies published in the last four years, summarized by design, population, outcomes, and statistical significance. Results: The reviewed studies suggest that ARNI therapy, when combined with CRT, may contribute to improvements in left ventricle ejection fraction (LVEF), NYHA functional class, and ventricular remodeling, particularly in CRT non-responders. Some studies also report a potential reduction in ventricular arrhythmias and implantable cardioverter-defibrillator (ICD) interventions. However, outcomes varied across subgroups, and the influence of ARNI timing relative to CRT implantation remains inconclusive. Limitations: Heterogeneity in study designs and small sample sizes in some included studies limited the ability to conduct a meta-analysis. This review is not registered. Conclusions: ARNI therapy shows promise in enhancing CRT response in patients with HFrEF, particularly in non-responders. Further large-scale, prospective studies are needed to clarify optimal patient selection and treatment sequencing.

Background/Objectives: Cardiac amyloidosis (CA) is an underdiagnosed and potentially life-threatening infiltrative cardiomyopathy characterized by the extracellular deposition of misfolded amyloid fibrils in cardiac tissue. It is most commonly associated with light-chain (AL) amyloidosis and transthyretin (ATTR) amyloidosis, either hereditary or wild-type. The disease often presents with non-specific symptoms, leading to delayed diagnosis and treatment. This study aims to provide a comprehensive overview of the pathophysiology, diagnostic strategies, and current therapeutic approaches for cardiac amyloidosis, with a focus on improving early detection and clinical outcomes. Methods: A narrative review was conducted using databases such as PubMed and Scopus, covering the period from September 2016 to March 2025. Keywords such as “cardiac amyloidosis”, “cardiac amyloidosis from transthyretin”, “cardiomyopathy”, “transthyretin”, “immunoglobulin light-chain amyloidosis”, and “familial amyloidosis” were used. Relevant clinical trials and guideline-based management recommendations were also included. Results: This review highlights that non-invasive imaging modalities and serum biomarker analyses are key to reducing diagnostic delays. New therapeutic developments, including gene-editing technologies and RNA-based therapies, show promise in early trials. Multidisciplinary management and increased awareness are crucial for timely diagnosis and treatment optimization. Conclusions: The early recognition of cardiac amyloidosis remains a major clinical challenge. Advances in non-invasive diagnostics and emerging disease-modifying therapies are transforming the prognosis of affected patients. Continued research and heightened clinical suspicion are essential to improve outcomes in this complex and heterogeneous disease.

Background: Sex-related differences in left ventricular (LV) reverse remodeling following ST-segment elevation myocardial infarction (STEMI) remain underexplored. We aimed to investigate predictors of reverse remodeling and its association with clinical outcomes, with a focus on sex-specific differences. Methods: We enrolled 253 STEMI patients (91 women, 28%) and assessed echocardiographic parameters at baseline and six months. LV reverse remodeling was defined as a ≥15% reduction in LV end-diastolic volume (LVEDV). Multivariate logistic regression identified independent predictors of remodeling. Clinical outcomes were evaluated over a median follow-up of 17 months (IQR 14–22 months), including major adverse cardiac events (MACEs). Kaplan–Meier and Cox regression analyses were performed. Results: Reverse remodeling occurred in 43% of patients and was more frequent in men than women (47% vs. 37%, p = 0.04). Male sex (OR 0.30; 95% CI: 0.14–0.65; p < 0.0001) and baseline global work efficiency (GWE) (OR 1.64; 95% CI: 1.45–1.85; p < 0.0001) were independent predictors. Men exhibited greater reductions in LVEDV, greater improvements in LV ejection fraction, and superior myocardial work indices. Over the follow-up, patients with reverse remodeling had significantly lower MACE rates compared to those without (10% vs. 24%, p < 0.01). Cox regression demonstrated that reverse remodeling was associated with a reduced risk of MACEs (HR 0.318; 95% CI: 0.181–0.557; p < 0.0001). Conclusions: LV reverse remodeling after STEMI is associated with improved clinical outcomes and is influenced by sex-specific differences. Baseline myocardial work indices, particularly GWE, are strong predictors of reverse remodeling. Men demonstrated a more favorable remodeling profile and myocardial recovery compared to women.

Heart failure (HF) remains a leading cause of morbidity and mortality globally, with increasing prevalence driven by aging populations and comorbidities such as diabetes mellitus. Recent advances have highlighted sodium-glucose cotransporter-2 (SGLT2) inhibitors, particularly empagliflozin and dapagliflozin, as effective agents in HF management across a broad spectrum of ejection fractions. Initially developed for glycemic control in type 2 diabetes, both drugs have demonstrated significant cardiovascular benefits, including reductions in HF hospitalizations and improvements in symptoms and quality of life. Their mechanisms extend beyond glucose lowering, involving natriuresis, osmotic diuresis, improved myocardial energetics, reduced sympathetic activation, and anti-inflammatory effects. While empagliflozin and dapagliflozin share a core renal mechanism via selective SGLT2 inhibition, subtle differences in pharmacokinetics, potency, and tissue selectivity may influence their clinical profiles. Emerging evidence suggests empagliflozin may confer stronger benefits in heart failure with reduced ejection fraction (HFrEF), while dapagliflozin could offer enhanced efficacy in heart failure with preserved ejection franction (HFpEF), although head-to-head comparisons are lacking. This review synthesizes current evidence comparing the mechanisms of action and clinical performance of empagliflozin and dapagliflozin in HF, providing insight into agent selection and future directions in therapy personalization.

Heart failure with reduced ejection fraction (HFrEF) continues to impose a high burden of morbidity and mortality despite significant advances in pharmacologic and device-based therapy. Cardiac resynchronization therapy (CRT) and angiotensin receptor–neprilysin inhibitors (ARNIs) have independently demonstrated substantial benefits in symptoms, health-related quality of life (HRQoL), and survival. Cardiac rehabilitation (CR), incorporating structured exercise, education, and lifestyle optimization, is well established as an effective intervention in HFrEF, yet its role in the era of combined CRT and ARNI therapy remains insufficiently characterized. This literature review synthesizes current evidence on CR in HFrEF populations receiving CRT, ARNI, or both, highlighting its impact on HRQoL, exercise capacity, and functional outcomes. Across diverse study designs—including randomized trials, observational cohorts, and meta-analyses—CR consistently yielded clinically meaningful improvements in patient-reported HRQoL and objective measures such as six-minute walk distance (6MWD) and peak oxygen uptake. Data directly evaluating CR in patients concurrently receiving both CRT and ARNI are lacking; indirect evidence suggests CR is compatible with, and may add to, contemporary device and drug therapy. However, referral rates remain low, indicating an implementation gap despite strong evidence of benefit. The review underscores the importance of integrating CR into contemporary HFrEF care and identifies a pressing need for targeted prospective studies to define its role in patients receiving dual device–pharmacologic therapy.

Cardiac resynchronization therapy (CRT) in sinus rhythm (SR) currently involves mandatory biventricular pacing with often simultaneous ventricular pacing (interval VV=0). While LV-only CRT has shown comparable efficacy, debates regarding its use continue. Main criticism is AV block occurrence in order to benefit fusion CRT pacing. Despite proved benefits, data on the incidence of AV block in patients receiving LV-only CRT without RV lead remain limited. AV block occurrence in such population could compromise CRT and require device upgrades to a biventricular system to ensure hemodynamic stability. To assess the incidence of AV block over long-term follow-up and the need for true biventricular pacing in patients with preserved baseline AV conduction undergoing LV-only CRT without an RV lead. A cohort of heart failure patients with preserved baseline AV conduction who met CRT-P indications received a dual-chamber DDD pacing system with leads in the right atrium (RA) and left ventricle (LV), omitting the RV lead. The primary endpoint was the incidence of AV block during long-term follow-up, evaluating the need for potential upgrades to a biventricular pacing system. Dosages of beta-blockers or ivabradine were optimized to stabilize the PR interval and promote fusion pacing. The study enrolled 135 participants with non-ischemic CRT fusion pacing and normal AV conduction, of which 87 CRT patients without RV lead were analyzed as final subgroup. Demographic data: 45 male, mean age 62 ± 11 years, with an average follow-up duration of 45 ± 19 months. During follow-up, two patients (2,3%) developed AV block requiring upgrades to biventricular pacing. The first patient, aged 60 years, developed AV block 27 months post-implant, while the second patient, aged 83 years, developed AV block at 107 months post-implant. No additional predictors of AV block were identified, and baseline characteristics were otherwise similar across patients. Of note, none of the other patients included in the study needed to pace RV for AV block which made the final incidence 1,5%. Long-term follow-up revealed a low incidence of heart failure progression-related mortality at 2.2%. Among the three patients who died, one developed severe aortic stenosis, while the other two died 9 and 7 years after CRT implantation, respectively. In patients with preserved AV conduction undergoing LV-only CRT, the incidence of AV block necessitating device upgrade to biventricular pacing was low (1,5%) and does not influence the outcome. These findings suggest that LV-only CRT may be a option for nonischemic patients with preserved AV conduction.

Background: Vascular dysfunction is increasingly recognized as a shared contributor to both cognitive impairment and late-life depression (LLD). However, the combined diagnostic value of cerebral hemodynamics, neuroimaging markers, and neuropsychological outcomes remains underexplored. This study aimed to investigate the associations be-tween transcranial Doppler (TCD) ultrasound parameters, cognitive performance, and depressive symptoms in older adults with mild cognitive impairment (MCI) and LLD. Importantly, we evaluated the integrative value of TCD-derived indices alongside MRI-confirmed white matter lesions (WMLs) and standardized neurocognitive and affective assessments. Methods: In this cross-sectional study, 96 older adults were enrolled including 78 cognitively unimpaired individuals and 18 with MCI. All participants underwent structured clinical, neuropsychological, and imaging evaluations including the Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), Geriatric Depression Scale (GDS-15), MRI-based Fazekas scoring of WMLs, and TCD ultrasonography of the middle cerebral artery. Hemodynamic variables included mean blood flow velocity (MBFV), end-diastolic velocity (EDV), pulsatility index (PI), and resistive index (RI). Logistic regression and receiver operating characteristic (ROC) analyses were used to identify independent predictors of MCI. Results: Participants with MCI showed significantly lower MBFV and EDV, and higher PI and RI (p < 0.05 for all) compared with cognitively unimpaired participants. In multivariate analysis, lower MBFV (OR = 0.64, p = 0.02) and EDV (OR = 0.70, p = 0.03), and higher PI (OR = 3.2, p < 0.01) and RI (OR = 1.9, p < 0.01) remained independently associated with MCI. ROC analysis revealed excellent discriminative performance for RI (AUC = 0.919) and MBFV (AUC = 0.879). Furthermore, PI correlated positively with depressive symptom severity, while RI was inversely related to the GDS-15 scores. Conclusions: Our findings underscore the diagnostic utility of TCD-derived hemodynamic parameters—particularly RI and MBFV—in identifying early vascular contributions to cognitive and affective dysfunction in older adults. The integration of TCD with MRI-confirmed WML assessment and standardized cognitive/mood measures represents a novel and clinically practical multi-modal approach for neurovascular profiling in aging populations.