Search Results (442)

Background: Right heart failure (HF) and tricuspid regurgitation (TR) are closely interrelated conditions, linked by a bidirectional and self-perpetuating pathophysiological relationship. Alterations in right-ventricular (RV) loading conditions, pulmonary vascular impedance, and ventriculo-arterial (VA) coupling play a central role in the development and progression of TR, which in turn exacerbates RV volume overload and end-organ dysfunction. Methods: This review provides a comprehensive overview of the pathophysiology of right HF and TR, focusing on the mechanisms underlying RV dysfunction, pressure–volume (PV) relationships, and pulmonary vascular load. We further examine the clinical implications of this interaction and summarize current strategies for risk stratification, with particular emphasis on disease-specific risk models. Results: TR emerges both as a consequence and a driver of RHF. Conditions such as pulmonary hypertension (PH) and left-sided heart disease promote annular dilation and leaflet tethering, leading to functional TR. Conversely, TR increases RV volume overload, worsening chamber dilation, reducing effective forward stroke volume (SV), and accelerating disease progression. This vicious cycle results in progressive RV impairment, impaired left-ventricular filling through ventricular interdependence, and systemic venous congestion affecting renal and hepatic function. Traditional risk scores fail to capture this complex pathophysiology. In this context, TRISCORE integrates clinical, biological, and echocardiographic (TTE) parameters reflecting RV dysfunction and systemic involvement, providing a more comprehensive assessment of disease severity and prognosis. Conclusions: TR should be considered not only a marker but also a key determinant of right HF progression. A multiparametric approach integrating pathophysiology and disease-specific risk stratification is essential to identifying the optimal therapeutic window and guiding clinical decision making. Full article

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. Full article

Background/Objectives: Excessive trabeculation of the left ventricle, previously known as left ventricular non-compaction (LVNC), is a rare phenotypic trait whose mechanisms and pathogenesis still remain conflictual. Its presentations may range from heart failure to embolism and, most importantly, ventricular arrhythmias (VAs). This study aims to find novel predictive factors for the occurrence of potentially fatal VAs in patients with left ventricular hypertrabeculation. Methods: All consecutive patients meeting the echocardiographic (Chin, Jenny or Stöllberger) and/or MRI criteria (Petersen) for hypertrabeculation were prospectively enrolled from October 2009 to December 2023. The primary outcome was a composite of sudden cardiac death, sustained ventricular tachycardias (sVTs), ventricular fibrillation (VF) or appropriate implantable cardioverter defibrillator (ICD) interventions. The secondary outcome was a composite of cardiovascular death and cardiovascular hospitalizations. Results: Overall, 64 patients (41 males, mean age 46 ± 19 years old) were enrolled and followed for a median time of 2.2 years. Six patients (9.4%) experienced a composite outcome at eight years, three with previous sVTs and three with previous non-sustained VTs (nsVTs). The strongest predictor of the primary endpoint was the anamnesis of nsVTs and sVTs before LVNC diagnosis. In addition, nsVTs and sVTs were significantly associated with the secondary outcome. Conclusions: Hypertrabeculation of the left ventricle is a complex and poorly understood condition whose status of cardiomyopathy is currently challenged. In our population, patients with a trabecular pattern experienced a high incidence of VAs, cardiovascular death and hospitalizations. VAs before LVNC diagnosis were predictive of the outcome independently from systolic function. Full article

Venoarterial extracorporeal membrane oxygenation (VA-ECMO) has failed to demonstrate mortality benefit in randomised controlled trials of cardiogenic shock. We aimed to determine whether a novel ‘Hemi-ECMO’ configuration, involving aortic occlusion to isolate the left ventricle from the VA-ECMO circuit, improves cardiac haemodynamics. We utilised a pulsatile biventricular mock circulatory loop with variable contractility to compare standard VA-ECMO with Hemi-ECMO support under left ventricular or biventricular failure conditions. When averaged across all pump speeds, mean left atrial pressure was significantly reduced with Hemi-ECMO compared to VA-ECMO (21.11 ± 1.32 mmHg vs. 26.53 ± 0.87 mmHg, p < 0.001), with more pronounced benefit at higher pump speeds. Aortic ejection increased with Hemi-ECMO at higher pump speeds: 0.14 ± 0.03 vs. 0.00 ± 0.00 L/min (p = 0.002) at 3000 revolutions per minute (RPM). Aortic ejection was greater with Hemi-ECMO in the descending aorta compared to the ascending aorta position (0.27 ± 0.03 L/min vs. 0.17 ± 0.05 L/min, p = 0.015). In conclusion, Hemi-ECMO demonstrates significant haemodynamic advantages in severe cardiogenic shock, including reductions in mean left atrial pressure and increases in aortic ejection, with greater benefits when positioned in the descending aorta. Further in vivo studies are warranted to assess clinical viability. Full article

Traditional cardiovascular assessment has historically focused on the isolated evaluation of either atrial or ventricular structure and function. However, the left atrioventricular coupling index (LACI) represents a paradigm shift by moving beyond single-chamber metrics to quantify the dynamic interaction between the left atrium and left ventricle. Defined as the ratio of left atrial end-diastolic volume to left ventricular end-diastolic volume, LACI integrates structural and functional aspects of cardiac performance. This comprehensive review examines the physiological basis of how the left atrium and ventricle operate as an integrated hemodynamic unit. We detail current measurement methodologies, including two- and three-dimensional echocardiography, cardiac computed tomography, and cardiac magnetic resonance imaging, which serves as the reference standard. Furthermore, the review explores the pathophysiological mechanisms driving atrioventricular uncoupling, specifically mechanical dysfunction, electromechanical desynchrony, and hemodynamic alterations. Extensive clinical evidence demonstrates LACI’s robust independent prognostic value across diverse cardiovascular conditions, such as heart failure, myocardial infarction, cardiomyopathies, and atrial fibrillation. Observational data suggest that LACI provides a promising prognostic value beyond established risk assessment tools by combining the assessment of both chambers’ interdependence. Finally, we outline future directions for clinical translation, highlighting the necessity for standardized measurement protocols, the integration of artificial intelligence, and the potential of LACI as a target for personalized therapeutic strategies. Full article

Patients with preload-dependent conditions are at high risk of hemodynamic instability from both hypovolemia and hypervolemia. In hypovolemic states, the presence of third spacing may be misleading and obscure true intravascular volume status. Therefore, management of critically ill patients should be guided by a thorough understanding of physiology and pathophysiology to appropriately address hemodynamic derangements. Overreliance on rigid protocols and protocol-driven care without adequate clinical judgment may, in some cases, adversely affect patient outcomes. Herein, we present a case of hypovolemia-induced hypotension in the setting of third spacing and concentric left ventricular hypertrophy. Full article

Background/Objective: Cardiac innervation plays a critical role in regulating myocardial function and enabling the heart to adapt to physiological and pathological conditions. Although the general features of sympathetic and parasympathetic innervation of the myocardium are well described, the spatial organisation of nerve fibres within the cardiac muscle remains incompletely characterised. This study aimed to develop and validate the SKUF (Slice–Keep–Unwrap–Fuse) protocol, a multimodal framework for mapping myocardial innervation through the integration of histological data and magnetic resonance imaging (MRI). Methods: The study was performed on the heart of a 7-year-old patient who died from rupture of a cerebral vascular malformation without evidence of cardiovascular disease. Prior to histological processing, post-mortem MRI was performed to provide a precise anatomical reference. The heart was sectioned into sequential transverse rings of 4 mm thickness, yielding 71 paraffin blocks. Histological sections (3 μm) were immunostained with antibodies against UCHL-1 to visualise nerve fibres and scanned using an Aperio AT2 system (20× magnification). Automated image analysis was conducted using the SVSSlide Processor module, which included tissue segmentation, colour-based nerve fibre detection, and sliding-window density mapping. Heatmaps were assembled into ring-based myocardial reconstructions and co-registered with MRI slices using combined rigid and deformable registration, followed by three-dimensional reconstruction of innervation patterns. Results: A higher density of nerve fibres was observed in the right ventricular myocardium compared with the left ventricle, whereas larger nerve trunks were identified in the epicardium of the left ventricle. Quantitative analysis revealed a pronounced longitudinal gradient of innervation, with minimal density in the apical region and progressive increases towards the mid-ventricular segments, where maximal density and spatial organisation of neural structures were observed. The atrioventricular groove exhibited the greatest heterogeneity of innervation due to the presence of large nerve trunks and ganglionated plexuses. Integration of histological maps with MRI enabled three-dimensional visualisation of spatial clusters of nerve fibres. Conclusions: The SKUF protocol provides a robust framework for integrating histological and MRI data to generate three-dimensional maps of myocardial innervation. This approach may facilitate the development of high-resolution anatomical atlases of cardiac innervation and support future studies of neurocardiac mechanisms of arrhythmogenesis and targeted neuromodulation. Full article

Cardiac and hemodynamic conditions such as myocardial infarct, cardiomyopathy, hypertension, and aortic valve disease can impair conduction within the Purkinje fiber network and compromise left ventricular (LV) pump function. We developed a computational framework that couples electrical propagation in a structurally organized Purkinje fiber network with LV electromechanics to analyze the impact of conduction abnormalities on cardiac performance. A baseline simulation reproduced physiological activation patterns and pump indices consistent with healthy human data. Conduction block was then introduced at different locations within the Purkinje fiber network. LV pump function was strongly dependent on block location: left bundle branch block (LBBB) produced the largest reduction in ejection fraction (EF) (59% to 46%) and peak pressure (119 to 97 mmHg), whereas left anterior fascicle block caused smaller functional changes. Across simulations, myocardial activation delay and systolic dyssynchrony index (SDI) exhibited a nonlinear relationship with EF and myocardial strain. A threshold behavior was identified at a simulated LV activation duration of approximately 240 ms and an SDI of 8.4%, beyond which EF and strain decreased by about 5% relative to baseline. These findings provide a mechanistic framework to investigate how Purkinje fiber network conduction abnormalities influence LV pump dysfunction. Full article

Background: Neonatal Ebstein’s anomaly (EA) is a severe condition with significant hemodynamic instability and early myocardial dysfunction, where abnormal right-heart geometry limits conventional echocardiography and highlights the value of myocardial deformation imaging. Methods: We conducted a single-center retrospective observational study including 16 neonates with EA and 26 healthy neonates. All subjects underwent comprehensive transthoracic echocardiography during the neonatal period. Conventional two-dimensional imaging and speckle-tracking echocardiography (STE) were used to assess biventricular and biatrial myocardial deformation. Deformation parameters were compared between groups, and receiver operating characteristic (ROC) curve analysis evaluated diagnostic performance. Results: Neonates with EA demonstrated significant structural remodeling and severe biventricular and biatrial dysfunction compared with controls. Speckle-tracking showed markedly reduced right ventricular longitudinal strain (LS) in all segments (all, p < 0.001), particularly in free-wall and four-chamber views. Left ventricular (LV) global LS (GLS) was significantly reduced in neonates with EA compared with controls (−14.53% vs. −22.32%, p < 0.001), indicating early involvement of LV myocardial function in the neonatal period. Atrial reservoir, conduit, and contractile strain were severely impaired in both atria (all, p < 0.001). ROC analysis revealed excellent diagnostic accuracy, especially for LVGLS (AUC 0.919) and right atrial contractile strain (AUC 0.958). Conclusions: STE enables the early detection of extensive biventricular and biatrial myocardial dysfunction in neonatal EA, including abnormalities not fully captured by conventional echocardiographic parameters, thereby providing significant incremental diagnostic value. Full article

Peripartum cardiomyopathy (PPCM) is a distinct condition that presents as heart failure (HF) in a woman who was previously healthy and has no prior cardiovascular issues. It results from idiopathic left ventricular (LV) dysfunction, characterized by a reduced LV ejection fraction below 45%. PPCM is a life-threatening condition with a high mortality rate (MR) that demands urgent treatment. Methods: This narrative review aims to define PPCM and its pathophysiology and conduct a scoping review of the latest data on the management of patients with peripartum cardiomyopathy during pregnancy and the postpartum period. Results: Currently, treatment follows standard HF protocols for reduced ejection fraction, with the possible addition of bromocriptine, and during pregnancy, medications that do not harm the fetus. Conclusions: Early, aggressive therapy is essential for a better prognosis, but managing PPCM can be challenging. Treatment of PPCM patients should be led by a team of highly qualified specialists, known as the Obstetric and Cardiac Care Team, comprising an obstetrician-perinatologist, an anesthesiologist, a cardiologist, and a cardiac intensive care specialist. Baseline left ventricular end-diastolic diameter (LVEDD) and left ventricular ejection fraction (LVEF) are the main prognostic factors. LVEF less than 30%, significant LV dilatation, LVEDD ≥ 6.0 cm, and right ventricular involvement are factors indicative of a poor prognosis. While pregnancy after PPCM is possible, it should be discouraged due to the significant risk of complications and even death. The most common causes of death in patients with PPCM are thromboembolic complications, severe HF, serious ventricular arrhythmias, cardiogenic shock, and sudden cardiac arrest. Full article

Background/Objectives: Infantile cardiomyopathy is a rare but often life-threatening condition in which monogenic causes are particularly relevant, especially when cardiac disease is preceded by hypotonia or multisystem involvement. Among sarcomeric genes, MYL2, encoding the ventricular regulatory myosin light chain, plays a critical role in myocardial contractility. However, biallelic MYL2-associated disease remains exceptionally rare, and its clinical spectrum is not fully defined. This study aims to describe a novel case and further delineate the phenotype of recessive MYL2-related cardiomyopathy. Methods: We report a male infant with congenital hypotonia and delayed motor development who underwent extensive metabolic, neuromuscular, and neuroimaging evaluation. Trio-based whole-exome sequencing was performed to identify a potential genetic etiology, followed by variant interpretation using standard bioinformatic and ACMG/AMP criteria. Results: The patient developed acute decompensated heart failure at approximately 10 months of age, with severe left ventricular systolic dysfunction and multiorgan failure, and died at 12 months despite maximal intensive care support. Whole-exome sequencing identified a homozygous MYL2 c.413T>A (p.Met138Lys) missense variant. The variant is absent or extremely rare in population databases, affects a highly conserved residue, is predicted to be deleterious by multiple in silico tools, and is compatible with autosomal recessive inheritance, with both parents confirmed as heterozygous carriers. In the context of a phenotype consistent with recessive MYL2-associated disease, these findings support a likely pathogenic interpretation. Conclusions: This case expands the allelic and phenotypic spectrum of recessive MYL2-associated cardiomyopathy and highlights the value of early genomic testing in infants with unexplained hypotonia and rapidly progressive cardiac dysfunction. Molecular diagnosis may aid in prognosis, clinical decision-making, and genetic counseling. Full article

Pulmonary hypertension is a progressive syndrome characterised by pulmonary vascular dysfunction, inflammation, maladaptive remodelling, and progressive right-ventricular strain. Translational progress remains limited because experimental models reproduce only selected aspects of the complexity of human disease. This narrative review evaluates naturally occurring canine disease as a comparative and spontaneous model of human pulmonary hypertension within a One Health framework. To achieve this, we synthesise recent human and veterinary literature, international consensus statements, and key registry and imaging studies. We outline current human definitions and diagnostic pathways based on right-heart catheterisation, together with the veterinary probability-based approach centred on echocardiography; compare epidemiology across species; and summarise contemporary mechanisms spanning vascular dysfunction, immune and metabolic signalling, and right-ventricular adaptation. We then examine canine conditions that parallel major human pulmonary hypertension phenotypes, including left-heart disease due to myxomatous mitral valve degeneration, fibrotic interstitial lung disease in West Highland White Terriers, sleep-related airway obstruction in brachycephalic breeds, and rare venous and capillary disorders. When combined, these spontaneous models provide opportunities to investigate disease-modifying techniques other than vasodilation and allow for the longitudinal, real-world evaluation of imaging, functional assessments, and circulating biomarkers. To improve care for both veterinary and human patients, we conclude by outlining priorities for mechanism-based clinical trials, shared outcome measures, prospective registries and biobanks, and harmonised definitions. Full article

Sudden cardiac death (SCD) is a major global health issue, defined as sudden natural death presumed to be of cardiac cause. While in the elderly SCD is commonly associated with coronary artery disease, in the younger population it is linked to inherited cardiomyopathies or channelopathies, even though SCD can remain unexplained even after a comprehensive autopsy in a substantial proportion of cases. In this context, genetic testing has gained importance, supported by the widespread availability of techniques such as next-generation and whole-exome/genome sequencing and their reduced costs. This state-of-the-art review summarizes the genetic bases of sudden cardiac death among cardiomyopathies, channelopathies and in sudden unexplained death presumed to be of arrhythmic cause. Among the structural causes, inherited cardiomyopathies such as hypertrophic, dilated, non-dilated left ventricular, arrhythmogenic right ventricular and restrictive ones represent major substrates for malignant ventricular arrhythmias mostly arising from variants in sarcomeric or desmosomal genes. Channelopathies (long or short QT syndrome, Brugada syndrome and catecholaminergic polymorphic ventricular tachycardia) are caused by variants in genes encoding cardiac ion channels and/or regulatory proteins, which equally predispose to high risk of life-threatening ventricular arrhythmias. In sudden arrhythmic death syndrome, with a structurally normal heart, post-mortem genetic testing (molecular autopsy) can uncover an underlying inherited condition. However, variants of uncertain significance are detected in more than half of the cases, underscoring the need for a multidisciplinary approach. Genetic testing also plays a key role in cascade screening of first-degree relatives. While monogenic variants drive risk in inherited cardiac disorders, emerging evidence suggests that polygenic contributions may modulate SCD susceptibility, highlighting future roles for polygenic risk scores in risk stratification. Full article

Background: Left ventriculo-arterial coupling (VAC) integrates the interaction between left ventricular contractility and the arterial system, representing a key determinant of cardiovascular efficiency. In rapidly changing hemodynamic states such as septic or cardiogenic shock, conventional indices of pressure or flow alone may be misleading. VAC provides a unified physiological framework to assess global cardiovascular performance and guide therapy. Objective: To review the physiological foundations, bedside assessment, and therapeutic applications of VAC in critically ill patients with rapidly fluctuating circulatory conditions. Methods and Content: The article revisits the underlying principles of VAC, expressed as the ratio between arterial elastance (Ea) and end-systolic elastance (Ees), and discusses their derivation from the pressure–volume relationship. Practical echocardiographic methods for bedside estimation, including the non-invasive single-beat approach, are outlined with illustrative figures. The review further examines how VAC patterns evolve in sepsis, cardiogenic shock, and heart failure and how this integrative index clarifies paradoxical responses to vasoactive and inotropic therapies. Specific therapeutic phenotypes are proposed according to Ea/Ees profiles, providing a structured approach to optimise coupling and restore circulatory efficiency. Summary: VAC offers a physiology-based perspective on cardiovascular performance, enabling clinicians to interpret complex hemodynamic changes beyond traditional measures of ejection fraction or mean arterial pressure. Its dynamic tracking may refine the assessment of therapeutic trajectories and improve bedside decision-making. Conclusions: By integrating ventricular and arterial function into a single measure, VAC bridges cardiovascular physiology and clinical practice. Its incorporation into routine critical care monitoring could enhance individualised hemodynamic management and serve as a foundation for future outcome-driven studies. Methodology: This narrative review was conducted using a structured literature search to ensure comprehensive coverage of contemporary evidence regarding ventriculo-arterial coupling (VAC) in critical care and shock states. A systematic search of PubMed/MEDLINE, Embase, and Scopus databases was performed from database inception through October 2025. The following key search terms were used: “ventriculo-arterial coupling”; “arterial elastance”; “end-systolic elastance”; “Ea/Ees”; “pressure–volume loops”; “septic shock”; “cardiogenic shock”; “critical care echocardiography”; “point-of-care ultrasound”; “mechanical circulatory support”. Reference lists of relevant articles, review papers, and consensus documents were also manually screened to identify additional pertinent studies. Only English-language publications were included. Both seminal foundational studies and recent contemporary investigations were reviewed to provide historical context and up-to-date clinical applicability. Full article

Aortic valve disease is increasingly recognized as a chronic, progressive condition in which the initial valve intervention exerts a decisive influence on all subsequent therapeutic options. The persistence of prosthesis–patient mismatch (PPM), often driven by implantation of small surgical prostheses (≤21–23 mm), is associated with higher residual transvalvular gradients, attenuated left ventricular reverse remodeling, inferior long-term survival, and compromised outcomes following valve-in-valve (ViV) transcatheter procedures. Accumulating clinical and imaging evidence indicates that aortic annular enlargement (AAE), particularly using contemporary Y-incision and extended “roof” reconstruction techniques, can safely and reproducibly expand the annulus, sinuses of Valsalva, and sinotubular junction, thereby permitting implantation of larger prostheses and substantially reducing the risk of PPM. Insights from computational fluid dynamics further demonstrate that annular and root enlargement favorably alters postoperative flow dynamics, resulting in lower peak velocities, reduced pressure gradients, and more physiologic flow patterns in both primary surgical valve replacement and simulated ViV settings. From a lifetime management perspective, valve diameter optimization emerges as a critical determinant of both immediate hemodynamic performance and future procedural feasibility. Surgical programs that adopt a systematic approach to anatomic assessment, valve sizing strategy, PPM surveillance, and ViV preparedness may achieve meaningful improvements in short- and long-term outcomes. This review integrates anatomic, operative, hemodynamic, and quality-oriented evidence to support consideration of valve upsizing as a central principle in contemporary aortic valve replacement. Full article