Abstract: Cardiovascular disease is traditionally interpreted through macrocirculatory parameters such as cardiac output, vascular resistance, and epicardial coronary anatomy. However, clinical outcomes frequently diverge from predictions based solely on these indices, particularly in syndromes such as heart failure with preserved ejection fraction (HFpEF), cardiogenic shock, and sepsis-associated myocardial dysfunction. Increasing evidence suggests that the integrity of the microvascular–immune interface plays a central role in determining tissue perfusion and cardiovascular resilience. This review proposes a staged framework of cardiovascular decompensation centered on progressive failure of this interface. In Stage 1, chronic cardiometabolic and inflammatory stress produces a primed but compensated microvascular state characterized by endothelial activation, glycocalyx vulnerability, pericyte remodeling, platelet sensitization, and reduced lymphatic reserve. Perfusion is preserved at rest, but vasodilatory reserve and microvascular stability are reduced, narrowing the effective perfusion window under physiologic stress. In Stage 2, acute insults such as infection, ischemia, or neurohumoral activation precipitate threshold instability within the microcirculation. Perfusion becomes governed by the arterial pressure–critical closing pressure (Pa − Pcrit) relationship rather than traditional arterial–venous gradients. As this window narrows, segmental capillary derecruitment and heterogeneous flow emerge, producing loss of hemodynamic coherence in which systemic blood pressure and cardiac output may appear preserved despite impaired tissue perfusion. In Stage 3, inflammatory amplification and immunothrombotic processes consolidate microvascular dysfunction. Pericyte contraction, endothelial injury, cytokine escalation, and neutrophil extracellular trap formation promote platelet–fibrin deposition and capillary obstruction, transforming reversible conductance failure into structural microvascular impairment. This framework provides a unifying physiologic lens for diverse cardiovascular syndromes, including Type 2 myocardial infarction, HFpEF decompensation, and cardiogenic shock. It also suggests that therapeutic efficacy may depend less on macrocirculatory normalization alone and more on preserving microvascular integrity before immunothrombotic consolidation occurs. Although this model remains hypothesis-generating, it highlights the microvascular–immune interface as a central determinant of cardiovascular stability and a potential target for future precision hemodynamic and immunomodulatory strategies.

Abstract: Supplemental oxygen is a cornerstone intervention in modern clinical practice, widely used to correct hypoxemia in emergencies, perioperative, and critical care settings. While oxygen therapy is lifesaving, accumulating evidence indicates that excessive oxygen exposure can induce significant pathophysiological disturbances, particularly within the cardiovascular and pulmonary systems. Hyperoxia (PaO₂ > 100 mm Hg) promotes the generation of reactive oxygen species (ROS), leading to oxidative stress, mitochondrial dysfunction, and activation of pro-fibrotic pathways. When combined with mechanical ventilation, these effects are further amplified through alterations in intrathoracic pressure, reduced venous return, and increased pulmonary vascular resistance, collectively imposing hemodynamic stress on the myocardium. These mechanical and biochemical perturbations converge to drive structural, functional, and electrical remodeling of the heart, including conduction abnormalities and arrhythmogenesis. Emerging clinical insights, particularly from critically ill and COVID-19 populations, underscore the importance of titrated oxygen strategies that balance adequate tissue oxygenation with minimization of hyperoxic injury. This review synthesizes current evidence on hyperoxia-induced oxidative stress, heart–lung interactions, and mechanisms underlying myocardial remodeling to provide a comprehensive framework for optimizing oxygen therapy.

Abstract: Background: Lipoprotein(a) [Lp(a)] is increasingly recognized as an independent and genetically determined cardiovascular risk factor. However, its clinical role in patients with established coronary artery disease (CAD), particularly in relation to premature disease onset, remains incompletely defined. This study aimed to evaluate the association between Lp(a) levels and early-onset CAD, as well as the relative contribution of Lp(a) compared with traditional cardiovascular risk factors. Methods: We conducted a retrospective observational study including 225 patients with established CAD admitted to a tertiary care center in 2023. Lp(a) levels were measured at admission. Patients were stratified according to revascularization strategy and age at first cardiovascular event (<50 vs. ≥50 years). Logistic regression and receiver operating characteristic (ROC) curve analyses were performed to assess associations and determine predictive performance. Results: Thirty-eight patients (17%) experienced early-onset CAD. Patients with early events showed significantly higher Lp(a) levels compared with those with later events (median 42 [19–75] vs. 21 [10–66] mg/dL; p = 0.020), despite lower LDL and non-HDL cholesterol levels. In multivariate analysis, both Lp(a) (OR 2.835, 95% CI 1.226–6.556, p = 0.015) and smoking (OR 2.516, 95% CI 1.116–5.673, p = 0.026) were independently associated with early-onset CAD. Lp(a) showed modest discriminative ability (AUC 0.619), with a cut-off value of 23 mg/dL providing 74% sensitivity and 52% specificity, and a high negative predictive value (91%). Lp(a) levels did not differ across revascularization subgroups. Conclusions: Elevated Lp(a) levels are independently associated with premature CAD, even in patients with lower traditional lipid risk factors and intensive lipid-lowering therapy. Routine Lp(a) assessment may improve cardiovascular risk stratification, particularly in younger patients.

Abstract: Minimally invasive aortic valve replacement (MIAVR) via transaxillary access, right anterior thoracotomy (RAT), and ministernotomy has matured from niche innovation to guideline-endorsed standard, yet comparative data remain heterogeneous and fragmented. Objectives: This state-of-the-art review synthesizes contemporary evidence to define the role of each approach within modern valve care pathways. A PRISMA 2020 systematic review with PROSPERO registration identified studies reporting outcomes of isolated AVR performed through transaxillary, RAT, or ministernotomy access. Primary endpoints were 30-day mortality, operative times, and length of stay; secondary endpoints included complications, long-term survival, learning curves, and patient-reported outcomes. Forty-two studies encompassing 15,328 patients were included: transaxillary (n=2,156), RAT (n=4,892), and ministernotomy (n=8,280). All approaches achieved excellent perioperative safety (mortality 0.4–2.5%) and long-term survival comparable to full sternotomy, while consistently reducing blood loss, transfusion, ventilation time, and hospital stay. Ministernotomy offered broadest anatomical applicability and the shortest learning curve (20–30 cases). RAT combined complete sternal preservation, lowest bleeding rates, and superior cosmetic and functional recovery in anatomically suitable patients. Transaxillary access provided hidden scarring and attractive options in redo or sternum-avoidance scenarios, but higher reported stroke rates (2.0–6.3%) and greater technical demands limited its use to high-volume centres. MIAVR via ministernotomy, RAT, and transaxillary access now represents a mature, durable alternative to full sternotomy. A structured, anatomy- and centre experience–driven selection strategy is essential to fully realize its benefits across diverse patient populations.

Abstract: Patients with cardiovascular diseases often require cardiac surgery with cardiopulmonary bypass (CPB), which triggers inflammation and increases the risk of postoperative atrial fibrillation (POAF). This study assessed the predictive value of inflammatory biomarkers and clinical and surgical variables for POAF in patients undergoing coronary artery by-pass grafting (CABG; n = 36), valve surgery (n = 40), or combined CABG and valve surgery (n = 13), all of whom utilized CPB. Levels of IL-6, IL-8, IL-10, and C-reactive protein (CRP) were measured preoperatively, at 24 and 48 hours postoperatively, and at discharge. Sta-tistical analyses included t-tests, Mann–Whitney U tests, correlation analysis, logistic regression, and receiver operating characteristic (ROC) curve analysis. Sixteen of 89 patients (18%) developed POAF between 48 and 72 hours after surgery. The Society of Thoracic Surgeons (STS) score and hemoglobin at 24 hours were significantly different (p < 0.05) between the POAF and non-POAF groups. At 24 hours, POAF patients had significantly higher IL-6, IL-8, and IL-10 levels (p < 0.02); IL-6 remained elevated at 48 hours (p < 0.05), while CRP declined at discharge (p = 0.05). A multivariable model including STS score, IL-6 at 24 hours, and postoperative magnesium yielded an AUC of 0.82, with an optimism-corrected AUC of 0.77 after internal bootstrap validation. Integrating inflammatory and clinical variables produced a robust predictive model.

Abstract: Background and Objectives: Infective endocarditis (IE) remains associated with high mortality, and real-world (RW) patients often differ from trial populations. We evaluated predictors of complications and mortality, the trial-eligibility gap, and temporal trends in guideline adherence across two periods (P1 2011–2016 vs P2 2017–2025) in a Romanian county hospital. Materials and Methods: We performed a retrospective analysis of consecutive adult patients with definite IE. Patients were categorized as trial-eligible (TE) or RW according to predefined criteria. The composite endpoint comprised acute heart failure, cardiogenic or septic shock, embolic events, infectious complications, need for renal replacement therapy, and in-hospital mortality. Guideline adherence was evaluated using a predefined quality indicator (QI) score ≥3. Independent predictors of outcome were identified using multivariable logistic regression. Results: Among 206 patients (mean age 63.0 ± 14.8 years; 70.4% male), blood cultures were positive in 64.1%, with Staphylococcus aureus accounting for 14.1%. Vegetations were documented in 72.8%, and cardiac surgery was performed in 26.2%. Overall, at least one event from the composite endpoint occurred in 61.6 %, and mortality was 32.5%. TE patients represented 63.1% of the cohort. Guideline adherence improved over time (QI ≥3: from 18.3% in P1 to 25.4% in P2 p=0.32). In the P2 period, the composite endpoint (66.8 % vs. 42.9%, p=0.002) and embolic events (31.8% vs. 8.2%, p< 0.001) were more frequent, whereas mortality remained unchanged (31.8% vs. 34.7%, p=0.844). Sepsis at admission and left ventricular ejection fraction < 50% independently predicted adverse outcomes; model discrimination was acceptable with an area under the curve (AUC) =0.77. Conclusions: Real-world IE showed high complication rates and a persistent trial gap; improved guideline adherence was counterbalanced by greater clinical severity.

Abstract: Background: Annuloplasty is a key component of mitral valve repair, yet ring selection remains heterogeneous and its impact on early outcomes is unclear. Methods: This retrospective study included 149 patients undergoing mitral valve repair in whom an annuloplasty ring was utilized. Ring designs were grouped into semi-rigid rings, semi-rigid bands, rigid rings, and other designs. The primary outcome was postoperative atrial fibrillation (AF). Secondary outcomes included early complications and repair durability based on follow-up echocardiography and mortality. Results: Postoperative AF occurred in 35.8% of patients and did not differ across ring designs (p = 0.244). In multivariable analysis, age was independently associated with AF (OR 1.06 per year, p = 0.001), whereas ring design was not. Early outcomes were favorable, with 2.0% mortality and 5.4% rethoracotomy. Follow-up echocardiography showed good or moderate repair in 96.0% of patients; overall repair failure occurred in 4.0% when including mortality, without a clear association with ring design. Conclusions: Annuloplasty ring design was not associated with postoperative AF or early outcomes. Patient-related factors, particularly age, appear more relevant, while early repair durability remains high.

Abstract: Background: Left bundle branch area pacing (LBBaP) has emerged as a physiological alternative to conventional biventricular pacing (BiVP) for cardiac resynchronization therapy (CRT). We aimed to compare long-term clinical, electrical, and echocardiographic outcomes of LBBaP versus BiVP in patients with heart failure with reduced ejection fraction (HFrEF). Methods: In this single-center retrospective study, 271 consecutive patients undergoing CRT implantation were included (LBBaP, n = 68; BiVP, n = 203). Outcomes included electrical resynchronization parameters, echocardiographic reverse remodeling, heart failure hospitalization, and all-cause mortality during a median follow-up of 41 months. Results: LBBaP achieved greater electrical resynchronization, with shorter postprocedural QRS duration (144 vs 153 ms; p = 0.005) and shorter left ventricular activation time compared with BiVP. LBBaP was associated with lower radiation exposure (124 vs 244 mGy; p < 0.001) and lower pacing thresholds. At 6 months, LVEF was higher in the LBBaP group (37.7% vs 33.0%; p = 0.005), and heart failure hospitalization occurred less frequently (22.6% vs 36.7%; p = 0.042). Long-term all-cause mortality did not differ between groups (p = 0.289). In multivariable analysis, baseline renal dysfunction and heart failure hospitalization within 6 months independently predicted mortality. Conclusions: In patients with HFrEF undergoing CRT, LBBaP provides superior electrical resynchronization and greater reverse remodeling compared with BiVP. Although associated with improved short-term clinical outcomes, long-term survival appears primarily determined by comorbid conditions rather than pacing modality.

Abstract: Introduction: Intermittent Claudication (IC), a painful manifestation of peripheral artery disease (PAD), is characterized by an imbalance between oxygen supply and demand in the lower limbs during physical activity and is associated with reduced walking capacity and health-related quality of life (HRQoL). Remote ischemic conditioning (RIC), a non-invasive intervention based on repeated cycles of limb ischemia and reperfusion, has been proposed to improve exercise tolerance in people with IC. However, the clinical effectiveness and safety of RIC in this population remain uncertain. Methods and Analysis: This protocol describes a systematic review and meta-analysis reported in accordance with the PRISMA-P statement. Electronic searches will be performed from 1986 to the most recent date prior to final analysis in MEDLINE, Embase, and CENTRAL. Eligible studies will include adults (≥18 years) with objectively confirmed PAD and IC, and classified as Rutherford categories 1–3 or Fontaine stages IIa–IIb. Participants with atypical claudication or with chronic limb-threatening ischemia will be excluded. Randomized controlled trials (RCTs) and non-randomized studies of interventions (NRSIs) will be included and synthesized separately. RIC will be compared with sham (placebo) interventions. Primary outcomes will include walking distance and time, and adverse events (AEs). Secondary outcomes will include physiological measures and HRQoL. Two reviewers will independently perform study selection and data extraction. Risk of bias (RoB) will be assessed using the Cochrane RoB 2 tool for RCTs and ROBINS-I for NRSIs. Certainty of evidence will be evaluated using the GRADE approach. Intervention characteristics will be described using the TIDieR checklist. Where appropriate, random-effects meta-analyses will use mean differences or standardized mean differences for continuous outcomes and risk ratios or odds ratio for dichotomous outcomes. Where meta-analysis is not feasible, results will be synthesized following SWiM guidance. Heterogeneity, subgroup, sensitivity, and exploratory analyses will be performed where data permit. Discussion: This review will synthesize evidence on the effectiveness and safety of RIC in people with IC to inform clinical decision-making and future research regarding the potential role of RIC as a rehabilitation intervention. Protocol registration: PROSPERO CRD42024566595. Funding: Publication costs are covered by Physioswiss (Swiss Association of Physiotherapy, Bern, Switzerland).

Abstract: The indispensable research finding of Liu et al. found that PIEZO2 in vagal ganglia contributes to cardiovascular stability by preventing orthostatic hypotension in a time-locked and fine-tuned way to atrial and ventricular systole. As part of this mechanism, a distinct group of vagal neurons with end-net endings in the heart initiate a blood-volume-dependent reflex in response to decreased filling of the heart to compensate upright posture and haemorrhage. After all, this robust feedback control counterbalances the impact of gravity to attain cardiovascular stability. The current commentary is meant to highlight that this mechanism is even more complex, and the finding is only one side of a coin, if we consider an underlying novel body-wide Piezo2 system, a Piezo2-coupled autonomic nervous system (ANS) and proprioceptive system, and the Piezo2-initiated ultradian backbone of the heart-brain axes. Hence, the knockout/ablation of PIEZO2 in vagal ganglia, as Lie et al[M1.1]. showed, critically targets this novel complex body-wide Piezo2 mechanism.

Abstract: Background: Emery–Dreifuss muscular dystrophy (EDMD) is a rare inherited neuromuscular disorder within the spectrum of nuclear envelope diseases, classically characterized by early musculo-tendinous contractures, slowly progressive myopathy and cardiac involvement dominated by conduction disease and arrhythmias, with variable evolution toward cardiomyopathy and heart failure. Methods: We performed a narrative synthesis of the contemporary literature, focusing on clinically relevant and high-impact evidence. Particular attention was given to diagnostic strategies, risk stratification, and therapeutic approaches applicable in real-world clinical settings. Results: Cardiac involvement in EDMD encompasses a broad spectrum, including atrial disease and conduction disturbances, ventricular arrhythmias, dilated cardiomyopathy, thromboembolic complications, and sudden cardiac death. The heterogeneity of phenotypic expression reflects underlying genetic diversity. Early recognition and systematic cardiovascular surveillance are essential to guide timely intervention, including device therapy and heart failure management. Despite growing awareness, significant gaps remain in risk prediction and standardized management pathways. Conclusions: EDMD represents a paradigmatic model of cardiomyopathy with prominent electrical instability and systemic implications. A structured, genotype- and phenotype-aware strategy, centered on early surveillance, targeted rhythm and thromboembolic risk management, and timely device therapy, can improve clinical decision-making in real-world settings. Future perspectives include the integration of precision medicine and the development of gene-targeted therapies, with the potential to shift from symptomatic management toward disease-modifying strategies. This narrative review aims to provide an updated and comprehensive, clinically actionable narrative synthesis of cardiovascular manifestations across EDMD genotypes and phenotypes, integrating rare and under-recognized high-impact presentations, and to outline pragmatic diagnostic and therapeutic pathways for real-world care while highlighting unmet needs and future directions.

Abstract: Sarcopenia is increasingly recognized as a key extracardiac manifestation of heart failure (HF), contributing to functional impairment, reduced quality of life, and adverse clinical outcomes. Characterized by progressive loss of skeletal muscle mass, strength, and physical performance, it affects more than half of hospitalized HF patients and is independently associated with increased mortality and reduced exercise capacity. The pathophysiology of sarcopenia in HF is multifactorial and closely linked to metabolic and nutritional disturbances. Chronic inflammation, neurohormonal activation, oxidative stress, endothelial dysfunction, and anabolic resistance contribute to muscle catabolism and impaired protein synthesis. These alterations are further exacerbated by inadequate dietary protein intake and micronutrient deficiencies, promoting progressive muscle wasting and functional decline. Sarcopenia may also represent an early and potentially modifiable stage in the continuum toward cardiac cachexia. This narrative review provides a comprehensive synthesis of current evidence on epidemiology, pathophysiological mechanisms, and management of sarcopenia in HF, with particular emphasis on nutritional and metabolic determinants. Emerging data support a multimodal therapeutic approach integrating exercise training with targeted nutritional strategies, including adequate protein intake, essential amino acid supplementation, and correction of micronutrient deficiencies. However, evidence from large, well-designed trials remains limited. In summary, improved recognition and integrated management of sarcopenia in HF are essential. Future research should focus on the development of effective, nutrition-centered therapeutic strategies.

Abstract: Genetic cardiomyopathies, encompassing hypertrophic cardiomyopathy and dilated cardiomyopathy, represent two of the most extensively characterized inherited cardiovascular disorders. Despite decades of mechanistic insight into sarcomeric dysfunction, calcium handling abnormalities, stress-responsive signaling cascades, and fibrotic remodeling, the translation of this knowledge into durable therapeutic success has remained uneven. A central but underappreciated challenge is the assumption that clinical pathogenicity inherently confers molecular stability that a variant classified as pathogenic will produce consistent downstream molecular perturbations across independent patient cohorts, disease stages, and biological contexts. We examine genetic cardiomyopathy biology through a translational lens, arguing that molecular stability and cross-cohort reproducibility must function as explicit development gates alongside mechanistic plausibility. We synthesize evidence across sarcomeric biology, calcium signaling, fibrosis, metabolic remodeling, and immune crosstalk, and critically appraise how biological heterogeneity, incomplete penetrance, and model limitations introduce translational risk. The expanding roles of multi-omics platforms and artificial intelligence-driven discovery are evaluated for both their promise and methodological fragility. Based on the available data and prevailing practices, a seven-step structured translational framework is proposed, operationalized through a five-domain Molecular Concordance Scoring Matrix that translates stability assessment into a scored, development-ready criterion. By reframing stability as a property of mechanism rather than a statistical afterthought, this framework aims to reduce late-stage development failure, improve biomarker reliability, and align therapeutic platform selection with the biological realities of genetically complex cardiac disease.

Abstract: Fatty acids are central to cardiac physiology, serving as both primary energy substrates and precursors for bioactive lipid mediators that shape myocardial structure and function. Essential n-3 and n-6 polyunsaturated fatty acids (PUFAs) are of particular interest because they give rise to prostaglandins, leukotrienes, and a diverse oxylipin network that regulates coronary tone, inflammation, thrombosis, and tissue remodeling in the heart. In parallel, non essential saturated, monounsaturated, and trans fatty acids modulate cardiomyocyte metabolism, membrane organization, and receptor microdomains, thereby influencing how these mediator pathways are engaged in health and disease. Clinically, n--3 long chain PUFAs such as eicosapentaenoic acid and docosahexaenoic acid have been associated with reduced cardiovascular mortality and more favorable post-ischemic remodeling, yet high-dose supplementation has also been linked to a modestly increased risk of atrial fibrillation. Conversely, diets enriched in industrial trans fats and excessive long-chain saturated fats promote dyslipidemia, endothelial dysfunction, and pro arrhythmic remodeling, and are consistently associated with higher rates of coronary artery disease, heart failure, and sudden cardiac death. At the mechanistic level, cardiac fatty acid handling is governed by coordinated uptake via CD36 and fatty acid transport proteins, mitochondrial β oxidation pathways, and nuclear receptor signaling through peroxisome proliferator-activated receptors, which together determine substrate preference, mitochondrial function, and oxidative stress. Superimposed on these core metabolic processes, cyclooxygenase, lipoxygenase, and cytochrome P450 epoxygenase pathways convert arachidonic acid and n 3 PUFAs into distinct repertoires of prostanoids, leukotrienes, hydroxyeicosatetraenoic acids, epoxyeicosatrienoic acids, and specialized pro resolving mediators that critically influence myocardial inflammation, fibrosis, electrophysiology, and repair. This review synthesizes experimental and clinical evidence on how specific fatty acid species and their oxylipin derivatives contribute to cardiac physiology and pathology, with emphasis on lipotoxic cardiomyopathy, heart failure phenotypes, ischemia–reperfusion injury, and arrhythmogenesis. We also evaluate interventional strategies—including dietary patterns, essential fatty acid supplementation, and pharmacological modulation of fatty acid uptake or oxidation—to optimize cardiac fatty acid and oxylipin metabolism. By framing fatty acids primarily through the lens of essential fatty acid biology and addresses key gaps in linking mechanistic lipid mediator pathways to cardiac outcomes.

Abstract: The coarctation of the aorta is a congenital anomaly characterized by a local narrowing of the aortic lumen localized near the ductus arteriosus. Typically diagnosed in child-hood, but it can remain until symptoms become evident. This aortic anomaly can also coexist with aortic valve stenosis. In our case report, we present a 46-year-old male with chest pain, dyspnea, and a significant blood pressure gradient between upper and lower extremities. Diagnostic examination included transthoracic echocardiography and computerised tomography. This diagnostic imaging showed narrowing of the aor-tic lumen with a residual lumen dimension of 3 mm and severe aortic stenosis. The pa-tient underwent a complex surgical procedure, replacment of the aortic valve and re-construction of the aorta. An extra-anatomic ascending to descending aortic bypass was constructed using a 20 mm Dacron graft, combined with mechanical aortic valve replacment. The operation was performed through median sternotomy with two arte-rial canula in the femoral artery and in the aorta, and one venous canula in the right atrium. Two canulae are placed for the safe performance of cardiopulmonary bypass. The patient was discharged at home without complication. This case highlights that a single surgical procedure may represent a definitive treatment of a complex problem with good short-term results.

Abstract: Contemporary clinical medicine relies on a risk-factor paradigm in which individual diseases are managed using population-derived thresholds. This reductionist approach is increasingly limited in cardiometabolic multimorbidity, where abnormalities arise from interacting dysregulations across cardiovascular, metabolic, renal, and endocrine systems, and interpretation of patient condition often requires an organism-level representation of physiological state. We introduce the digiphysiomic framework, which proposes a transition from isolated risk-factor management to a multidimensional state-space representation centered on physiological expression mapping. In this framework, patient condition is represented as a point in a coordinate system defined by measurable and therapeutically relevant physiological processes. Clinical measurements are transformed into a normalized phenotype vector relative to reference models derived from population and clinical datasets. A knowledge-informed weighting structure—refinable using observational data, randomized trials, and guideline-based evidence—defines the geometry of the space and enables construction of the physiological expression map, a structured visualization of regulatory imbalance designed to support mechanism-oriented clinical decision making. Cardiometabolic disease provides a representative application because it inherently involves multiple interacting regulatory systems. The digiphysiomic space can be constructed using routinely collected clinical variables together with measurements previously used in physiological and hemodynamic phenotyping studies, while maintaining a stable coordinate structure that allows heterogeneous datasets to be integrated without redefining physiological dimensions. Within this space, longitudinal change and therapeutic effects can be represented as transitions, enabling alternative treatment strategies to be compared within a unified physiological framework. By establishing an explicit physiological coordinate system centered on the physiological expression map, the digiphysiomic framework may provide an intermediate layer between raw clinical data and predictive algorithms. Prior work on multidimensional physiological phenotyping and mechanism-guided therapy supports the feasibility of this representation, and with further validation, this approach may support future AI-assisted decision-support systems for individualized management of cardiometabolic multimorbidity while remaining consistent with clinical reasoning and guideline-based care.

Abstract: Introduction: Anemia is common in heart failure patients. It has been associated with an increased risk of hospitalization, morbidities, and considerable mortality in heart failure patients, making its correction an important element in improving the quality of life and clinical outcomes of patients. The magnitude of anemia and its associated factors among heart failure patients were not explored in the study setting. This study aimed to assess the prevalence of anemia and its associated factors among chronic heart failure patients at Asella referral and teaching hospital in southeast Ethiopia. Methods: This cross-sectional study included 264 heart failure patients who visited the cardiac follow-up clinic at Asella referral and teaching hospital, Southeast Ethiopia. A systematic random sampling method was used to select the study participants. Logistic regression analysis was used to assess factors associated with anemia in chronic heart failure patients. Statistical significance was declared at a p-value < 0.05. Results: The overall anemia prevalence was 27.3% (95% CI: 21.98, 32.6) among chronic heart failure patients. Age ≥ 60 years (AOR = 3.17, 95% CI: 1.02-9.87), female sex (AOR = 2.56, 95% CI: 1.31-5.01), utilization of angiotensin converting enzyme inhibitors (ACEIs) (AOR = 3.81, 95% CI: 1.81-7.94), history of previous hospitalization (AOR = 2.23, 95% CI: 1.31-5.01), and higher New York Heart Association (NYHA) functional class (class III (AOR = 2.81, 95% CI: 1.21-6.55), class IV (AOR = 6.38, 95% CI: 1.29-13.57)) were significantly associated with anemia among heart failure patients. Conclusion: This study revealed that the prevalence of anemia among chronic heart failure patients was high. Improved screening protocols and tailored interventions addressing older patients, females, patients taking ACEIs, and patients with advanced heart failure are essential for enhancing early detection and management of anemia in chronic heart failure patients to reduce associated morbidity and mortality.

Abstract:

Objectives: Quantifying ventricular secondary mitral regurgitation (MR) remains challenging, and the prognostic value of echocardiographic parameters is uncertain. This study aimed to assess the concordance of parameters of MR severity and determine the added value of regurgitant fraction (RF) in predicting outcomes. Methods and results: We retrospectively analysed 186 patients with ventricular secondary MR who underwent echocardiography with MR assessment, evaluating effective regurgitant orifice area (EROA), regurgitant volume (RegVol) and RF. The primary endpoint was a composite of all-cause death or heart failure hospitalisation. Quantitative parameters of MR severity were frequently discordant. Using the guideline-recommended cut-offs for EROA (≥ 40 mm²), RegVol (≥ 60 ml) and RF (≥ 50%), severe MR was present in 5.4%, 3.3%, and 29.5% of patients, respectively. Both RF ≥ 50% and EROA ≥ 40 mm² were independently associated with clinical outcomes in multivariable Cox models. Combining RF and EROA provided incremental prognostic value over either parameter alone (p < 0.05). Kaplan-Meier curves showed that patients with EROA < 40 mm² and RF ≥ 50% had similar outcomes to those with EROA ≥ 40 mm² (p = 0.055), whereas patients with both EROA < 40 mm² and RF < 50% had significantly better outcomes (p = 0.002). Conclusions: Substantial discordance between quantitative parameters of severe MR was observed in ventricular secondary MR. RF is a strong, underutilised marker of MR severity, reflecting haemodynamic burden beyond EROA and RegVol. Patients with EROA < 40 mm² and RF > 50% had outcomes comparable to those who met guideline-based threshold for severe MR, defined as EROA ≥ 40 mm². Our results demonstrate that routine RF assessment enhances risk stratification and enables identification of a high-risk subgroup of patients with EROA < 40 mm².

Abstract: Revascularization of the circumflex artery territory is challenging due to its anatomical position and technical complexity. We present a novel approach using the proximal circumflex trunk for arterial bypass, ensuring natural antegrade blood flow and avoiding multiple distal anastomoses. This streamlined technique minimizes grafting complications and achieves efficient revascularization in complex left main disease.

Abstract: Bigorexia, or muscle dysmorphia, is an increasingly prevalent body image disorder among adolescents characterized by an excessive drive for muscularity. This behavioral phenotype is associated with a cluster of lifestyle exposures—including anabolic androgenic steroid use, high energy drink consumption, and excessive high-protein diets—that may collectively promote early cardiovascular injury. Emerging evidence suggests that these factors contribute to a distinct cardiovascular phenotype marked by premature atherosclerosis, pathological left ventricular hypertrophy, and increased arrhythmogenic risk. Despite growing recognition of bigorexia as a psychological condition, its cardiovascular implications remain underexplored. This review synthesizes current evidence linking bigorexia-related behaviors to cardiovascular dysfunction and proposes a conceptual framework for this emerging phenotype, highlighting the need for early recognition, risk stratification, and targeted preventive strategies.