Search Results (1,327)

Objectives: This multicenter cross-sectional study investigated the relationship between age and organ-specific iron burden and characterized multi-organ iron phenotypes across different age groups in adults with non-transfusion-dependent thalassemia (NTDT). Methods: We retrospectively evaluated 96 adults with NTDT enrolled in the multicenter Italian Extension-Myocardial Iron Overload in Thalassemia network. Hepatic, pancreatic, and cardiac iron burden were assessed by quantitative magnetic resonance imaging (MRI). Results: The median age was 41.64 (36.08–53.92) years. Hepatic iron overload (IO) was present in 59.4% of patients and pancreatic IO in 29.2%, whereas no patient exhibited myocardial IO. Age was not associated with liver iron concentration (LIC) or cardiac R2*. A weak positive correlation was observed between age and pancreatic R2* (R = 0.215, p = 0.035), although this association was no longer significant after the exclusion of one extreme value. LIC and pancreatic R2* were not correlated. Across age groups (<40, 40–59, and ≥60 years), the prevalence of pancreatic IO increased (22.9%, 28.6%, and 50.0%, respectively), whereas hepatic IO remained stable. Isolated hepatic IO was the most common phenotype overall, while combined hepatic and pancreatic IO was more frequent among patients aged ≥60 years. Conclusions: In adults with NTDT, age was not associated with greater hepatic or cardiac iron burden, whereas older patients showed a higher prevalence of pancreatic iron accumulation and combined hepatic–pancreatic iron involvement. These findings highlight the organ-specific heterogeneity of iron distribution in NTDT and support the role of multi-organ MRI assessment beyond LIC evaluation, particularly in older patients. Full article

Background: Pulmonary hypertension (PH) is associated with increased pulmonary arterial pressure and impairment of right ventricular (RV) function. Reliable characterization of RV performance is important for prognosis, risk assessment, and therapeutic planning. Cardiac magnetic resonance (CMR) is considered the reference technique for quantifying RV volumes and function, but its expense and limited availability can restrict routine implementation. Echocardiography is more widely accessible; however, the extent to which individual echocardiographic indices correspond with CMR-derived RV ejection fraction (RVEF) remains incompletely defined. Objective: Our objective was to determine the correlation of RV fractional area change (RV-FAC), RV free-wall longitudinal strain (RV-FWLS), and RV global longitudinal strain (RV-GLS) with CMR-derived RVEF in individuals with PH. Methods: PubMed, Embase, ClinicalTrials.gov, Scopus, and the Cochrane Library were searched, yielding 404 records; six studies fulfilled the eligibility criteria. Studies were eligible when they enrolled patients with PH and provided extractable correlations between at least one prespecified echocardiographic measure and CMR-derived RVEF. Correlation coefficients were converted with Fisher’s z transformation, combined using common-effect and random-effects approaches, and then transformed back to correlation coefficients. Pooled mean RV-FAC was evaluated as a separate outcome. Between-study heterogeneity was quantified with I² and τ², with random-effects estimates emphasized for interpretation. Results: Each evaluated echocardiographic measure was positively correlated with CMR-derived RVEF. RV-FWLS had the largest pooled correlation and the greatest consistency (r = 0.79, 95% CI: 0.73–0.83; I² = 0.0%). The pooled correlation for RV-GLS was 0.75 (95% CI: 0.60–0.85; I² = 80.3%), while that for RV-FAC was 0.72 (95% CI: 0.61–0.80; I² = 61.8%). The random-effects pooled mean RV-FAC was 31.10% (95% CI: 26.77–35.43), with substantial heterogeneity (I² = 90.9%). Conclusions: RV-FWLS showed the highest numerical and most consistent association with CMR-derived RVEF, suggesting that it may serve as a useful non-invasive adjunct for RV assessment in PH, especially where CMR is not readily available. Larger studies using harmonized acquisition and analysis methods are required for confirmation. Full article

Background/Objectives: N-terminal pro-B-type natriuretic peptide (NT-proBNP) is an established heart failure biomarker, but its associations with cardiac magnetic resonance (CMR) parameters in patients with reduced ejection fraction remain unclear. This study examined the associations between serum NT-proBNP concentrations and CMR-derived functional, structural, and tissue characterization parameters in patients with HFrEF and evaluated which imaging parameters remained associated with NT-proBNP after multivariable adjustment. Methods: This retrospective single-center study included 92 consecutive patients with HFrEF who underwent CMR and NT-proBNP measurement within a 24 h window, with a median absolute interval of 6 h (range, 1–15 h) between the two assessments. CMR analysis included left ventricular ejection fraction (LVEF), left ventricular and left atrial (LA) cavity diameters, myocardial mass, extracellular volume fraction (ECV), the late gadolinium enhancement (LGE) burden, and the T2 signal intensity (T2-SI) ratio. Spearman correlation, univariate linear regression, and multivariable linear regression analyses were performed using log-transformed NT-proBNP values. Results: Log NT-proBNP demonstrated significant correlations with LVEF (r_s = −0.359, p < 0.001), T2-SI ratio (r_s = −0.332, p = 0.001), ECV (r_s = 0.383, p < 0.001), and LA diameter (r_s = 0.347, p < 0.001). No statistically significant correlations were observed between log-transformed NT-proBNP and LGE burden, LV cavity diameter, myocardial mass, LV wall thickness, age, or the recorded comorbidities. In multivariable analysis, LVEF, T2-SI ratio, and LA diameter remained associated with NT-proBNP after adjustment for the available covariates. Conclusions: Lower LVEF, a lower T2-SI ratio, and a larger LA diameter were associated with higher NT-proBNP levels in patients with HFrEF. The T2-SI ratio and LA diameter should be considered exploratory imaging markers requiring prospective validation. Full article

Congenital coronary artery anomalies, whether native, associated with structural heart defects, or acquired following surgical repair, are an increasingly recognized cause of morbidity and sudden cardiac death in the expanding adult congenital heart disease (ACHD) population. Their clinical significance is heightened as the first generation of arterial switch operation (ASO) recipients reaches adulthood. This review presents a practical, evidence-based framework for the classification, multimodality imaging evaluation, risk stratification, and surgical and interventional management of coronary anomalies across the ACHD spectrum. Recommendations from the 2025 ACC/AHA and 2020 ESC guidelines are synthesized, key divergences in the approach to asymptomatic patients are highlighted, and critical knowledge gaps, including emerging technologies and the uncertain long-term coronary outcomes of the ASO generation, are discussed. Full article

Objectives: The presence of a bicuspid aortic valve (BAV) is known to alter transvalvular flow and increase shear stress on the ascending aorta, contributing to alterations in aortic geometry and the progression of BAV-related aortopathy. The purpose of the current study was to characterize aortic flow abnormalities and their associations with aortic geometry and ventricular mechanics using cardiac magnetic resonance imaging (CMR). Methods: In this prospective cross-sectional study, 56 young adults with CMR-confirmed BAV and 56 age- and sex-matched healthy volunteers underwent standardized CMR. Biventricular volumes and function, LV global longitudinal strain (LV-GLS), LV torsional mechanics, ascending aortic geometry, pulse-wave velocity, aortic distensibility, and two-dimensional phase-contrast-derived forward and backward flow parameters were quantified. Associations between myocardial mechanics and haemodynamic variables were assessed using correlation analyses and multivariable linear regression. Results: Compared with healthy controls, patients with BAV exhibited preserved LV ejection fraction but impaired LV-GLS, reduced LV torsion, increased aortic stiffness, and a significantly greater backward-flow burden despite similar net aortic flow (all p < 0.001). Higher peak backward-to-forward flow-rate ratios were associated with less negative LV-GLS (p = 0.006), whereas greater aortic regurgitant volume was also associated with impaired longitudinal deformation (p = 0.001). In multivariable analysis, LV-GLS and aortic regurgitant volume remained associated with the peak backward-to-forward flow-rate ratio within the specified model, whereas ascending-aortic dimensions were not. The final model explained 52% of the variability in backward-flow burden. Conclusions: CMR identified a subclinical ventricular-aortic phenotype in young adults with BAV characterized by altered LV mechanics, increased aortic stiffness, and greater relative backward-flow burden despite preserved conventional LV systolic function. The association between backward-flow burden and LV longitudinal mechanics suggests that these abnormalities may represent interrelated manifestations of BAV disease; however, their temporal and causal relationships cannot be established from this cross-sectional study. Full article

Both fibrosis and hypertrophy contribute to abnormal myocardial mechanics in hypertrophic cardiomyopathy (HCM). We sought to assess the relationships between regional structural and functional parameters in HCM by cardiac magnetic resonance (CMR). This was a retrospective single-center study of HCM patients and age-matched controls with either hypertensive heart disease (HHD) or normal CMRs. CMR feature tracking was performed to assess global and segmental 2D-radial, circumferential, and longitudinal LV strain, while native and post-contrast T1 parametric mapping analysis was performed to assess the global and regional T1 values and ECV fraction. Of 100 patients (age 56 ± 15 years; 66% male), 62 were in the HCM group and 38 in the control group (19 healthy individuals and 19 with HHD). Compared to the control group, global circumferential strain (−16.1 ± 5.9% vs. −20.8 ± 3.6%, p < 0.001) and radial strain (45.2 ± 14.1% vs. 32.1 ± 14.0%, p < 0.001) were worse in the HCM group. Among the HCM patients, there were significant correlations between segmental native T1 values at the most hypertrophied segment and global longitudinal strain (r = 0.27, p = 0.031), global circumferential strain (r = 0.34, p = 0.006), global radial strain (r = −0.29, p = 0.024), and left ventricular ejection fraction (LVEF) (r = −0.31, p = 0.014). In HCM, higher myocardial T1 at the most hypertrophied segment correlated with worse global LV myocardial strain and LVEF by CMR. Full article

Background: Sodium-glucose cotransporter 2 (SGLT2) inhibitors, originally developed as glucose-lowering agents for type 2 diabetes mellitus, have been shown in large, randomized trials to improve clinical outcomes in heart failure (HF) across the ejection fraction (EF) spectrum. The imaging-derived and hemodynamic changes that accompany these benefits remain incompletely characterized, and it is not known whether the patterns of cardiac remodeling observed differ between HF with reduced ejection fraction (HFrEF, left ventricular ejection fraction [LVEF] ≤ 40%) and HF with preserved ejection fraction (HFpEF, LVEF ≥ 50%). This systematic review synthesized randomized evidence on the effects of SGLT2 inhibitors on cardiac remodeling parameters and described the patterns observed in each phenotype. Methods: PubMed/MEDLINE, Scopus and Embase were searched for randomized controlled trials (RCTs) published between February 2016 and March 2026. Eligible studies enrolled adults with chronic HF receiving an SGLT2 inhibitor, included a non-SGLT2-inhibitor comparator and assessed cardiac structure, function or loading by echocardiography, cardiac magnetic resonance (CMR) or cardiac catheterization over at least three months. Risk of bias was assessed with Cochrane RoB 2, separately for each outcome domain and targeting the effect of assignment to intervention, and certainty of evidence with GRADE, separately by phenotype and imaging modality. A structured narrative synthesis following Synthesis Without Meta-analysis (SWiM) guidance that prioritized the direction, magnitude and precision of randomized between-group treatment effects was performed. Results: Fourteen publications from thirteen unique RCTs (1232 participants) were included: four trials enrolled HFrEF (LVEF ≤ 40%), five enrolled mixed reduced and mildly reduced EF cohorts (LVEF < 50% or 35–49%), four enrolled HFpEF (LVEF ≥ 50%) and one enrolled a mixed ejection-fraction population. No trial enrolled an exclusively HFmrEF population. In reduced EF, the direction of effect on LV volumes favored SGLT2 inhibition in four of eight trials reporting volumes, but the estimates were not compatible in magnitude, and the one adequately powered trial at low risk of bias (EFFORT) was neutral; the largest volumetric estimates came from EMPA-TROPISM, which published no adjusted between-group estimate. The only prespecified, adjusted and confidence-interval-bearing volumetric estimates were those of SUGAR-DM-HF (left ventricular end-systolic volume index −6.0 mL/m², 95% CI −10.8 to −1.2; end-diastolic volume index −8.2 mL/m², 95% CI −13.7 to −2.6). The global longitudinal strain improved in the trial with blinded core-laboratory reading (EFFORT −1.44%, 95% CI −2.42 to −0.46), but effect sizes in the open-label trials without stated reader blinding were two to three times larger, and the CMR-derived strain was unchanged. In HFpEF, volumes, EF, mass and strain were unchanged throughout. The most secure finding of the review was invasive: in CAMEO-DAPA, dapagliflozin reduced pulmonary capillary wedge pressure at rest by 3.5 mmHg (95% CI −6.6 to −0.4) and at peak exercise by 5.7 mmHg (95% CI −10.8 to −0.7). NT-proBNP results were directionally inconsistent, and the trials in which NT-proBNP was a prespecified primary endpoint (Empire HF, CANDLE) were neutral. Certainty of evidence was very low for 18 of 20 evidence profiles and low for the remaining two. Conclusions: Randomized imaging and hemodynamic studies suggest phenotype-related differences in the cardiac remodeling associated with SGLT2 inhibitor therapy. In studies enrolling patients with reduced EF, treatment was associated predominantly with reverse remodeling of left ventricular volumes and modest improvements in myocardial function, whereas in preserved EF, the observed changes were mainly confined to filling pressures and diastolic function, with no consistent evidence of left ventricular volumetric remodeling. Given the limited number of studies, substantial heterogeneity, and the overall low certainty of evidence, these findings should be considered hypothesis-generating and warrant confirmation in adequately powered phenotype-specific mechanistic trials. Full article

Cardiac electrophysiology (EP) is inherently data-centric, spanning brief 12-lead electrocardiograms (ECGs), high-density electroanatomic maps, and continuous device-based monitoring. This data volume can strain provider workflows while creating an opportunity for artificial intelligence (AI). Machine learning (ML) and its deep learning subfield extract clinically actionable patterns from complex electrical signals. This narrative review summarizes contemporary AI applications across the major domains of EP. In arrhythmia detection, deep neural networks classify rhythms at a level comparable to cardiologists on internal test sets, identify occult atrial fibrillation (AF) from a normal sinus-rhythm ECG, and, through consumer wearables, extend screening to ambulatory populations. In catheter ablation, an AI algorithm that adjudicates intracardiac electrogram dispersion improved single-procedure freedom from AF in a randomized trial of persistent AF, and ML models help predict arrhythmia recurrence; we distinguish these from adjacent non-AI technologies, such as computed-tomography integration and three-dimensional mapping, that reduce fluoroscopy but are not themselves AI. In cardiac implantable electronic devices (CIEDs), AI-based filtering lowers false-positive alert burden, and multi-parametric algorithms provide earlier prediction of heart-failure decompensation. ML models may refine patient selection for cardiac resynchronization therapy (CRT) and, using late-gadolinium-enhancement cardiac magnetic resonance, may sharpen arrhythmic-risk and implantable cardioverter-defibrillator (ICD) decision-making. AI-enhanced ECG broadens the standard ECG into a low-cost screening tool for channelopathies, dyskalemias, and ventricular dysfunction. Important barriers remain, including limited external validation, incomplete explainability, and a scarcity of prospective outcome trials. Full article

Pulmonary hypertension (PH) is a heterogeneous clinical syndrome in which similar haemodynamic abnormalities may arise from distinct vascular, cardiac, pulmonary, thromboembolic, and molecular mechanisms. This complexity limits the ability of conventional classifications and risk scores to fully capture individual disease trajectories and treatment responses. Artificial intelligence (AI) offers a framework for integrating clinical data, electrocardiography, multimodal imaging, invasive haemodynamics, biomarkers, and multi-omics information across the PH care pathway. This review summarises current applications of machine learning and deep learning in early detection, diagnostic referral, right-ventricular and pulmonary vascular phenotyping, molecular endotyping, risk stratification, and therapeutic decision support. Available studies show promising results for AI-assisted electrocardiographic screening, automated echocardiographic and cardiac magnetic resonance analysis, computed tomography (CT)-based phenotyping, and multimodal prognostic modelling. True multi-omics integration in PH remains limited to discovery studies and has not yet yielded externally validated endotype or treatment-response classifiers. Evidence maturity is task-dependent: screening and phenotyping span several PH groups, whereas validated risk tools, molecular endotyping, and pathway-directed therapy remain predominantly PAH-based, particularly in idiopathic/heritable PAH. However, most evidence remains retrospective, derives from selected referral populations, and lacks robust external or prospective validation. No AI-based model currently supports routine drug selection or autonomous clinical decision-making. Future progress will require harmonised multicentre datasets and standardised acquisition protocols, transparent and interpretable models, and prospective studies demonstrating meaningful clinical benefit. AI should therefore be viewed as an emerging decision-support tool that may strengthen precision medicine in PH while complementing clinical expertise across diagnosis, phenotyping, risk assessment, and therapeutic stratification pathways. Full article

Cardiac involvement in systemic sclerosis (SSc) is mechanistically heterogeneous, driven by concurrently operative processes spanning right ventricular dysfunction, pulmonary microvascular remodeling, and mitochondrial damage. The existing literature rarely synthesizes these domains simultaneously, leaving substantive gaps in mechanistic understanding and the clinical management of SSc cardiac disease. An integrative review of original primary research was conducted using PubMed, Scopus, and Web of Science. Search terms combined “systemic sclerosis,” “right ventricular dysfunction,” “echocardiographic strain,” “pulmonary microvascular disease,” “nailfold capillaroscopy,” “mitochondrial dysfunction,” “oxidative stress,” and “cardiac biomarkers.” Eligible articles were required to report original empirical findings in SSc or SSc-related pulmonary arterial hypertension populations, encompassing echocardiographic, microvascular, molecular, or biomarker outcomes. Right ventricular function is compromised across multiple echocardiographic dimensions—from an elevated myocardial performance index and impaired ventriculoarterial coupling to prognostically significant speckle-tracking strain abnormalities—independent of overt pulmonary hypertension. Pulmonary microvascular disease, quantified by nailfold capillaroscopy and flow-mediated dilation, correlates directly with cardiac magnetic resonance tissue characterization in SSc-related pulmonary arterial hypertension. Mitochondrial dysfunction involving respiratory chain impairment, abnormal fusion dynamics, and altered mitochondrial DNA (mtDNA)copy number is demonstrable across dermal fibroblasts, monocytes, and immune cell populations. Circulating cardiac biomarkers complement echocardiographic findings and predict cardiopulmonary mortality. The integrative framework linking right ventricular remodeling, peripheral vasculopathy, and mitochondrial injury offers substantially richer insight into SSc cardiac pathophysiology than any single-domain perspective can provide, with direct implications for early detection and therapeutic targeting. Full article

Background: Cardiac sarcoidosis (CS) is a potentially life-threatening manifestation of systemic granulomatous disease, characterized by a heterogeneous spectrum of arrhythmic and conduction disorders that represent the leading cause of CS-related sudden cardiac death (SCD). Clinical cardiac involvement is estimated at 5% of sarcoidosis patients, while silent myocardial infiltration is detected in 20–25% of autopsy series. Diagnosis is difficult because the disease frequently runs a subclinical course and no single test is pathognomonic. Methods: PubMed and Embase were searched to 5 August 2026 for this narrative review, incorporating peer-reviewed articles, international guidelines (HRS 2014, JCS 2016, AHA/ACC/HRS 2017, ESC 2022, AHA 2024, the 2024 European clinical consensus statement and the 2025 ESC guidelines on myocarditis and pericarditis), and registry data. Results: Atrioventricular (AV) block occurs in 23–30% of CS patients and frequently requires permanent pacing. Fatal ventricular arrhythmia rates reach 20.7% at 5 years and 31.9% at 10 years (ILLUMINATE-CS registry, n = 512). Late gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR) performs well diagnostically (pooled sensitivity 95%, specificity 85%) and is associated with an odds ratio of 10.74 for arrhythmic events. 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) provides complementary value for guiding immunosuppressive therapy and pre-ablation risk assessment. Implantable loop recorders enable early arrhythmia detection in patients not yet meeting implantable cardioverter-defibrillator (ICD) criteria. Conclusion: Optimal management of arrhythmias in CS requires a multimodal diagnostic approach integrating electrocardiography, advanced cardiac imaging, and continuous rhythm monitoring. Risk stratification for SCD remains the central challenge, requiring individualized decision-making that integrates left ventricular ejection fraction (LVEF), imaging biomarkers, and electrophysiological data. Future prospective studies should aim to refine predictive risk algorithms, assess the role of emerging immunomodulatory agents such as JAK/STAT inhibitors, and validate artificial intelligence (AI)-assisted tools intended to identify cardiac involvement and arrhythmic risk earlier in the disease course. Full article

Background: Myocardial infarction (MI) remains a leading cause of morbidity and mortality despite major advances in reperfusion and secondary prevention. Inflammation contributes throughout the MI continuum, from atherosclerotic plaque development and destabilization to myocardial injury, adverse ventricular remodeling, and recurrent cardiovascular events. Objective: This narrative review summarizes current evidence on inflammation across the MI continuum, focusing on inflammatory biomarkers, cardiovascular imaging, residual inflammatory risk, and emerging anti-inflammatory therapies. Methods: We reviewed current evidence on the pathophysiological and clinical relevance of inflammation in MI, with particular emphasis on circulating biomarkers, multimodality imaging, and inflammation-targeted therapeutic strategies. Results: High-sensitivity C-reactive protein remains the best-established biomarker of residual inflammatory risk, while interleukin-6, myeloperoxidase, suPAR, and GlycA provide complementary information. Advanced imaging, including coronary computed tomography-derived perivascular fat attenuation index, cardiac magnetic resonance, and positron emission tomography, may further characterize vascular and myocardial inflammation. Clinical trials support inflammation as a potentially modifiable component of cardiovascular risk; however, therapeutic benefit has been inconsistent across inflammatory targets, agents, and clinical settings. Canakinumab and low-dose colchicine have demonstrated cardiovascular benefit in selected secondary-prevention populations, although recent neutral trials highlight heterogeneity across clinical settings. Similarly, IL-6-targeted strategies have yielded mixed results, with the neutral ZEUS trial underscoring that biomarker reduction does not necessarily translate into cardiovascular benefit, while NLRP3-targeted approaches remain investigational. Conclusions: Integrating inflammatory biomarkers, multimodality imaging, and targeted therapies may improve risk stratification and support personalized secondary prevention. Further evidence is needed to define optimal patient selection and determine whether biomarker- or imaging-guided anti-inflammatory strategies improve clinical outcomes. Full article

Background: Myocardial infarction (MI) causes spatially heterogeneous loss of contractility and progressive extracellular matrix remodeling, altering left ventricular mechanics from the acute phase through chronic remodeling. This review integrates current understanding of infarct, border-zone, and remote-myocardial microstructure with organ-scale mechanics and patient-specific computational modeling. Methods: A narrative review and perspective were conducted using the literature identified through PubMed/MEDLINE, Scopus, and Web of Science, supplemented by targeted searches of IEEE Xplore and Google Scholar. Experimental, imaging, computational, and translational studies were synthesised, with emphasis on post-MI constitutive behaviour, finite-element and growth-and-remodeling models, imaging-informed personalization, inverse parameter estimation, identifiability, model calibration, verification and validation, and uncertainty quantification. No quantitative synthesis was performed because of substantial heterogeneity in study populations, imaging modalities, constitutive formulations, boundary conditions, calibration procedures, and reported outcomes. Results: Contemporary post-MI models can reproduce ventricular volumes, regional strain patterns, and selected haemodynamic measures, while enabling counterfactual simulations of infarct stiffness, border-zone contractility, and loading interventions. However, clinically credible prediction remains constrained by limited in vivo observability of regional tissue properties, poor parameter identifiability, confounding between material properties and loading conditions, and incomplete treatment of measurement, parameter, and model-form uncertainty. Conclusions: The novelty of this review lies in framing post-MI patient-specific modeling as an identifiability- and uncertainty-limited inverse problem rather than solely as a model-fitting exercise. It proposes that translation toward decision-grade prediction requires parsimonious models aligned with a defined clinical context of use, constrained by microstructure-informed priors, multimodal pressure–volume–strain data, longitudinal validation, and routine reporting of parameter identifiability and predictive uncertainty. Full article

Late gadolinium enhancement (LGE) cardiac magnetic resonance is the reference standard for non-invasive myocardial tissue characterization. Conventional LGE analysis focuses on the presence and extent of fibrosis, yet these measures incompletely describe the spatial complexity of myocardial scar that underpins arrhythmogenesis. Entropy, derived from radiomic analysis of LGE signal-intensity distributions, has emerged as a surrogate marker of myocardial tissue heterogeneity. Mechanistically, heterogeneous fibrosis promotes electrical conduction alterations, and entropy serves as a global descriptor of this complex substrate. A growing body of evidence suggests that higher LGE entropy is associated with increased arrhythmogenicity and major adverse cardiac events. Several studies have shown that this association remains significant after adjustment for conventional clinical and imaging predictors. A smaller number of studies have gone further, demonstrating that incorporation of LGE entropy improves the discriminatory or reclassification performance of established risk-prediction models. This narrative review critically synthesizes the current evidence on LGE-derived entropy, compares methodological approaches and clinical applications, and discusses its principal limitations. After standardization and prospective validation, entropy-based phenotyping may prove useful for individualized risk stratification beyond conventional LGE metrics and guide clinical decision-making. Full article

Background/Objectives: Idiopathic Carpal Tunnel Syndrome (CTS) can be an early manifestation of systemic amyloidosis, particularly transthyretin cardiac amyloidosis (ATTR-CA). The primary purpose of this retrospective case series was to describe the presence of amyloid deposits in tenosynovial tissue and explore potential cardiac involvement in patients undergoing carpal tunnel release surgery. Methods: From a cohort of 54 patients diagnosed with bilateral idiopathic CTS with surgical indication, 12 patients were selected for tenosynovial tissue samples, which were subsequently evaluated using Congo red staining and proteomic confirmation via mass spectrometry. Before the procedure, patients underwent a clinical assessment of medical history, electrocardiogram, and cardiac scintigraphy with Technetium-99 m 3,3-diphosphono-1,2-propanodicarboxylic acid (^99mTc-DPD). Transthoracic echocardiogram and cardiac magnetic resonance were subsequently performed in all patients with positive scintigraphy, while a subset of scintigraphy-negative patients underwent an echocardiogram. Results: Congo red staining identified amyloid deposits in 3 of the 12 patients (25%). Proteomic analysis confirmed ATTR amyloidosis deposits in 2 of these patients (17%). One of these 2 patients presented Perugini grade 3 uptake on cardiac scintigraphy, suspicious for ATTR-CA. Complete concordance across histology, proteomics, and cardiac imaging was observed in only 1 patient (8.3%). Three discordances were noted: one case of tenosynovial ATTR without evident cardiac disease, one patient with a discordant Congo red result likely reflecting low amyloid burden or tissue heterogeneity, and one with imaging findings suspicious for ATTR-CA despite a negative tenosynovial biopsy. Conclusions: Tenosynovial biopsy obtained during CTS surgery can reveal early amyloid deposition, which may precede overt cardiac involvement. The variability observed across findings underscores the need for a multimodal diagnostic approach that integrates histological, proteomic, and imaging data, thereby mitigating the risk of amyloidosis misclassification. Full article