Abstract: Cardiorenal syndrome type 1 (CRS-1) is defined as acute kidney injury (AKI) caused by acute decompensated heart failure (ADHF). Heart failure with preserved ejection fraction (HFpEF) is an increasingly prevalent subtype of heart failure. A significant number of patients with HFpEF during episodes of acute decompensation (ADHFpEF) develop CRS-1. The most important pathophysiological mechanisms leading to the development of CRS-1 in these patients are hemodynamic disturbances (elevated central venous pressure, elevated intra-abdominal pressure and pulmonary hypertension) and inflammation. Loop diuretics alone or in combination with thiazide diuretics and mineralocorticosteroid receptor antagonists are the mainstay therapeutic option for treating congestion in patients with ADHFpEF and CRS-1. Introducing SGLT-2 inhibitors as soon as clinically possible can further enhance diuresis and have a positive impact on reducing cardiorenal adverse events. Development of CRS-1 is a well known independent predictor of a worse outcome in patients with heart failure, although this impact appears to be less associated in patients with HFpEF, as compared to patients with HF with reduced EF. Further studies are needed to achieve a better understanding of pathophysiological mechanisms, and to introduce new treatment protocols, which would have a positive impact on cardiac and renal outcomes in these patients.

Abstract:

Background/Objectives: Valve-in-valve transcatheter aortic valve implantation (ViV-TAVI) is an established treatment for failed surgical aortic bioprostheses, but dedicated data on the MyVal platform remain limited. We evaluated outcomes, hemodynamics, residual gradient, and an exploratory matched comparison with ACURATE neo2. Methods: This prospective, single-center cohort included consecutive patients with failed surgical aortic bioprostheses treated with MyVal ViV-TAVI between July 2022 and June 2025. Outcomes were reported according to VARC-3. Results: Sixty-eight patients were included (age 77 ± 7 years; 51.5% women; EuroSCORE II 7.3 ± 1.8%). Technical success was 100%, with no 30-day death, stroke, myocardial infarction, second-valve implantation, or emergency surgical conversion. Mean gradient decreased from 38.0 ± 9.5 mmHg at baseline to 6.7 ± 2.1 mmHg post-procedure and remained low at 1 year (8.1 ± 2.5 mmHg; overall p<0.001). AVA increased from 0.80 ± 0.23 cm² to 1.98 ± 0.19 cm² post-procedure and was 1.86 ± 0.23 cm² at 1 year (overall p<0.001). Smaller true internal diameter independently predicted elevated 1-year gradient (adjusted OR per 1-mm decrease 1.33, 95% CI 1.04–1.78; p=0.028). In the exploratory matched comparison, safety and hemodynamic outcomes did not differ significantly between MyVal and ACURATE neo2. At a median follow-up of 12.8 months, all-cause mortality and heart failure hospitalization were each 4.4%. Conclusions: MyVal ViV-TAVI showed high procedural success and durable 1-year hemodynamic performance, with residual gradient driven mainly by small surgical valve true internal diameter.

Abstract: Myocardial ischemia-reperfusion (I/R) injury represents a major clinical challenge in cardiothoracic surgery, notably during cardiopulmonary bypass, coronary artery bypass grafting (CABG), and orthotopic heart transplantation. The complex pathophysiology underlying I/R injury involves severe disruptions in protein dynamics, pronounced inflammatory cascades, and the induction of cellular apoptosis. Emerging molecular evidence highlights the critical regulatory roles of non-coding RNAs (ncRNAs)—specifically microRNAs (miRNAs) and long non-coding RNAs (lncRNAs)—alongside damage-associated molecular patterns (DAMPs), or alarmins, in orchestrating these processes. This review provides a comprehensive analysis of the molecular interplay between ncRNAs and alarmins during myocardial I/R injury. It delineates how the dysregulation of these molecules alters proteostasis, amplifies oxidative stress, and initiates perioperative inflammatory pathways. Furthermore, we summarize recent preclinical and clinical findings that identify specific ncRNAs (e.g., miR-1, miR-21, and MALAT1) and alarmins (e.g., HMGB1) as viable, targeted therapeutic avenues. Modulating these targets offers a promising approach to mitigating myocardial damage, enhancing cardioprotection, and improving surgical outcomes. Future investigations must prioritize translating these molecular targets into clinically feasible cardioprotective strategies.

Abstract: Background Long-term stent healing after primary PCI of culprit unprotected left main (ULM) lesions is insufficiently explored. In this setting, large vessel size and bifurcation anatomy may limit angiographic stent optimisation and contribute to persistent strut malapposition and incomplete coverage. Objectives To identify OCT-derived geometric and healing parameters associated with long-term strut coverage and malapposition after angiography-guided primary PCI of culprit ULM lesions. Methods This single-center exploratory study included 30 patients with long-term OCT follow-up after angiography-guided primary PCI of culprit ULM lesions. OCT analysis was performed separately in three prespecified subsegments: the left main (LM), polygon of confluence (POC), and distal main branch (dMB). Five predefined strut-level healing outcomes were analysed: covered struts, malapposed struts, malapposed and uncovered struts, significantly malapposed struts (>400 μm), and significantly malapposed and uncovered struts. Associations between patient-level healing outcomes and OCT-derived measures of lumen geometry, stent dimensions, neointimal response, and an exploratory lumen–stent mismatch variable were assessed using univariable and multivariable linear regression. Results A total of 31,703 struts were analysed. Overall strut coverage was 90.7 ± 6.6%. Compared with the dMB, proximal ULM segments (LM and POC) showed lower strut coverage (82.8% and 84.2% vs. 93.9%, p< 0.001) and higher malapposition rates (17.4% and 14.2% vs. 0.4%, p< 0.001). In regression analysis, larger native lumen dimensions were associated with lower strut coverage and higher malapposition, whereas larger achieved stent area was associated with better strut healing. The exploratory lumen–stent mismatch variable was independently associated with all five healing outcomes in multivariable models (all p < 0.01). Conclusions After angiography-guided primary PCI of culprit unprotected left main lesions, long-term strut healing was significantly influenced by the mismatch between native reference lumen area and the achieved minimum stent area. Whether intravascular imaging–guided optimization of stent sizing and expansion in large-calibre left main anatomy improves strut healing requires further investigation.

Abstract: Cardiovascular diseases remain the leading cause of mortality worldwide, with coronary artery disease being the most significant contributor. The management of coronary artery disease, including stable ischemic heart disease and acute coronary syndrome, through non-surgical revascularization procedures has been widely practiced and extensively discussed in the literature, particularly regarding the benefits of complete revascularization. Complete revascularization has been associated with better prognostic outcomes and improved functional capacity in patients compared to incomplete revascularization. This study aims to compare the functional capacity, as measured by the six-minute walk test (6MWT), between patients undergoing complete and incomplete revascularization. The study employed a cross-sectional design and was conducted at Prof. Dr. R.D. Kandou General Hospital, Manado, within the Division of Cardiac Prevention and Rehabilitation. The study population consisted of hospitalized coronary artery disease patients who had undergone revascularization procedures and completed the 6MWT. Data collection took place from October 2020 to October 2023, yielding a total sample of 303 patients. The findings of this study demonstrate a significant difference in the functional capacity, as assessed by the 6MWT, between patients who underwent complete and incomplete revascularization procedures. Patients who underwent complete revascularization exhibited better functional capacity, as indicated by the greater distance covered during the 6MWT, compared to those who underwent incomplete revascularization.

Abstract: Background Aorto-right ventricular fistula (ARVF) secondary to membranous septum rupture is an exceptionally rare complication after surgical aortic valve replacement (SAVR). While sutureless prostheses such as the Perceval valve have gained wide acceptance due to reduced cross-clamp times and procedural simplification, reported adverse events predominantly include conduction disturbances and paravalvular leaks. Structural septal disruption remains sparsely described. We report a case of early ARVF after Perceval implantation and review the pathophysiological and procedural mechanisms implicated in septal injury following sutureless and transcatheter aortic valve interventions. Case Description A 66-year-old woman with severe bicuspid aortic valve stenosis underwent SAVR via median sternotomy using a Perceval XL prosthesis after meticulous annular decalcification and sizing. Immediate intraoperative transesophageal echocardiography (TEE) confirmed optimal seating without paravalvular regurgitation. Within 24 hours, the patient developed complete atrioventricular block followed by cardiogenic shock. Repeat TEE revealed a large ARVF with significant left-to-right shunt. Emergent re-exploration identified a membranous septum tear. The Perceval prosthesis was explanted, the defect closed with reinforced patch repair, and a 27 mm Inspiris Resilia bioprosthesis was implanted. Peripheral veno-arterial ECMO support was required temporarily. The patient recovered and remained free of prosthetic dysfunction at two-year follow-up. Discussion Membranous septum rupture after AVR has an estimated incidence of 0.4-1.5 % in TAVR cohorts but is virtually unreported with Perceval valves. Mechanisms include chronic radial stress from oversized or malpositioned prostheses. Case reports with TAVR devices emphasize oversizing as a risk factor. Predictive factors for septal injury in sutureless AVR mirror those for conduction disturbances: valve oversizing, shallow infra-annular septal length, heavy calcification, and prior valve surgery. Preventive measures: strict sizing protocols, avoidance of balloon dilation, and optimized implantation depth, have reduced conduction complications and may mitigate septal trauma. Treatment choice percutaneous versus surgical closure, depends on hemodynamic stability, defect size and anatomy, and operative risk. Conclusion Early ARVF after Perceval implantation is exceedingly rare but potentially catastrophic. Strict adherence to sizing principles, awareness of septal anatomy, and prompt management, percutaneous in selected stable cases or surgical in acute large defects, are essential to optimize outcomes in sutureless AVR.

Abstract: A single paragraph of about 200 words maximum. For research articles, abstracts should give a pertinent overview of the work. We strongly encourage authors to use the following style of structured abstracts, but without headings: (1) Background: Place the question addressed in a broad context and highlight the purpose of the study; (2) Methods: briefly describe the main methods or treatments applied; (3) Results: summarize the article’s main findings; (4) Conclusions: indicate the main conclusions or interpretations. The abstract should be an objective representation of the article and it must not contain results that are not presented and substantiated in the main text and should not exaggerate the main conclusions.

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.