Background The in‐hospital trajectories of left ventricular ejection fraction (LVEF) in patients admitted for acute heart failure have been poorly investigated. We sought to assess the rate of heart failure with improved ejection fraction (HFimpEF) at discharge in acute heart failure, to identify predictors of HFimpEF and to evaluate the association of HFimpEF with outcome. Methods We retrospectively enrolled patients admitted for acute heart failure, with ≥2 in‐hospital echocardiographic evaluations of LVEF and with LVEF ≤40% at admission. HFimpEF was defined as LVEF >40% at discharge, with an improvement in LVEF ≥10%. The primary end point was 1‐year all‐cause death. Trajectories of LVEF were also assessed at follow‐up ambulatory visit at 1 year after discharge. Results The overall population included 779 patients with LVEF ≤40% at admission; at discharge, 14.9% had HFimpEF. The independent predictors of HFimpEF were valvular heart disease (odds ratio, 3.460; P=0.001), lower left ventricular volumes (odds ratio, 0.957 per 1 mL/m2 increase; P<0.001), and absence of right ventricular dysfunction (odds ratio, 0.518; P=0.017). LVEF at admission was not associated with 1‐year all‐cause death. When patients were classified according to the in‐hospital LVEF trajectory, HFimpEF was independently associated with a lower risk of 1‐year (hazard ratio [HR], 0.324; P=0.008) and 5‐year all‐cause death (HR, 0.584; P=0.013). Among patients discharged with HFimpEF who were reevaluated after 12 months, 86% maintained LVEF >40%, while 14% showed again LVEF ≤40%. Conclusions In patients with acute heart failure admitted with LVEF ≤40%, 15% had HFimpEF at predischarge reassessment. Valvular pathogenesis of heart failure with reduced ejection fraction, absent right ventricular dysfunction and less severe left ventricular remodeling were associated with higher likelihood of in‐hospital HFimpEF. One‐year and 5‐year mortality risk was lower in patients with HFimpEF compared with patients with nonimproved LVEF.

AIMS:Hypertrophic cardiomyopathy (HCM) shows variable left ventricular hypertrophy, yet current diagnostic criteria rely on absolute wall thickness (WT) cut-offs that may miss early or subtle phenotypes, particularly in sarcomere mutation carriers. OBJECTIVES:To determine whether wall thickness standard deviation (WTSD), reflecting WT heterogeneity, improves identification of HCM and mutation carriers. METHODS AND RESULTS:Cardiac magnetic resonance was performed in 382 healthy controls, 297 patients with HCM, 82 sarcomere mutation carriers without overt hypertrophy, and 180 patients with other cardiac conditions (75 with and 105 without LV hypertrophy). End-diastolic WT was measured in 16 myocardial segments, and WTSD was computed. Diagnostic performance was compared with other WT-derived parameters using age- and sex-specific thresholds. WTSD was higher in HCM (4.3 ± 1.1 mm) and mutation carriers (2.3 ± 0.3 mm) than in controls (1.3 ± 0.3 mm; P < 0.0001). WTSD identified 97% of HCM and 64% of carriers with 99% specificity. In females, WTSD achieved 98.9% sensitivity and 100% specificity for HCM and detected 74% of carriers. WTSD outperformed demographic-based thresholds and BSA-indexed maximal WT in all subgroups. Mutation carriers showed heterogeneous remodelling with both hypertrophic and thinned segments despite normal absolute WT. WTSD was significantly higher in HCM than in all cardiac conditions with LV hypertrophy and in mutation carriers vs. non-hypertrophic conditions, except post-ischaemic severe LV dysfunction. CONCLUSION:WTSD is a robust imaging biomarker that detects both overt and early sarcomeric HCM with high accuracy. Incorporating WT heterogeneity into diagnostic algorithms may enhance early identification, especially in women and mutation carriers.

Nonylphenol (NP) is a chemical compound belonging to the class of alkylphenols (APs), known for its widespread environmental distribution and endocrine-disrupting properties. It is commonly used in the production of detergents, pesticides, and plastic materials and, owing to these properties, it can accumulate in both aquatic and terrestrial ecosystems. As a xenoestrogenic compound, NP can bind steroid receptors, including estrogen receptors (ERs), thereby activating ER-dependent pathways. In this work, we investigated the effects of NP alone and in combination with the endogenous hormones 17β-oestradiol (E2) and/or testosterone (T) on a human non-tumoral prostate cell line (PNT1A). Cell viability and migration assays, together with analysis of ER expression and localization, were carried out to assess the xenoestrogenic activity of NP, particularly in the presence of E2 and T. Our results showed that NP retained its endocrine-disrupting features in the mixtures, positively affecting cell viability, except for the NP+E2 mixture, in which cell viability did not significantly differ from control, suggesting an antagonistic interaction between NP and E2. The mixtures also interfered with steroid receptor dynamics, affecting receptor expression and delaying receptor localization and activation kinetics. Moreover, all mixtures negatively affected cell migration compared with treatment with endogenous hormones alone. In conclusion, our results demonstrate that NP retains its xenoestrogenic behavior in mixture, inducing a significant alteration in prostate cell homeostasis.

Hypertrophic cardiomyopathy (HCM) is a major health concern, with cardiac magnetic resonance (CMR) playing a crucial role in risk assessment. We investigated for the first time the utility of sequential CMR, particularly strain analysis, for tracking HCM progression. We retrospectively evaluated HCM patients undergoing two CMR scans over a 10-year period. We measured changes in left ventricular (LV) strain parameters and examined their yearly changes as predictors of a composite of sudden cardiac death, life-threatening ventricular arrhythmias, stroke, new-onset atrial fibrillation, and heart failure hospitalizations. Patients (n = 114) were predominantly male (73%), with a median age of 51 years (interquartile range 36-60), obstructive HCM in 14%, and a median HCM risk score of 2% (1-3%). Only one patient (0.9%) had LGE >= 15% on the first scan, while 8 (7.0%) had LGE >= 15% after a median of 5.1 years (3.5-6.5). Absolute changes in LV strain displayed significant relationships with changes in LGE mass (longitudinal strain: beta = 0.227, p = 0.016; circumferential strain: beta = 0.421, p < 0.001; radial long-axis: beta=-0.261, p = 0.006). During a 4.3-year median follow-up after the second CMR scan (interquartile range 2.2-6.9), 40 patients experienced an event; hard arrhythmic events were infrequent. Among patients with LGE < 15% at baseline, yearly absolute changes in radial short-axis strain predicted outcomes beyond baseline HCM score and LGE extent (hazard ratio 1.12, 95% confidence interval 1.03-1.22, p = 0.011). In patients with predominantly early-stage HCM, worsening short-axis radial strain was associated with composite adverse events after the second CMR, independent of baseline LGE and ESC SCD risk.

Critically ill patients in the intensive care unit (ICU) require continuous hemodynamic monitoring to guide therapeutic decisions and prevent clinical deterioration. Echocardiography has emerged as a cornerstone for noninvasive hemodynamic assessment, offering real-time, bedside evaluation of key parameters such as venous congestion, pulmonary pressures, left atrial pressure (LAP), systemic vascular resistances, cardiac output, and ventricular-arterial coupling. Systemic venous congestion and right atrial pressure (RAP) can be assessed through inferior vena cava diameter measurement and respiratory variation, with additional accuracy provided by the VeXUS score, which incorporates hepatic, portal, and renal vein Doppler profiles. Internal jugular vein assessment and left ventricular (LV) stroke volume variability further refine RAP estimation. Pulmonary hypertension (PH) and right ventricular dysfunction can be evaluated through echocardiographic markers that differentiate precapillary from postcapillary PH, enabling tailored treatment strategies. In addition, echocardiography is fundamental for detecting right ventricular failure, particularly in PH and cardiogenic shock. LAP and systemic hemodynamics are integral to assessing LV diastolic and systolic dysfunction, which are pivotal in heart failure and cardiogenic shock management. Echocardiography also provides insights into vascular system properties and their interaction with cardiac performance, while lung ultrasound aids in detecting interstitial edema of cardiac origin. As a fast, reliable, and reproducible tool, echocardiography is the gold standard for noninvasive hemodynamic assessment in ICU patients, facilitating prompt and precise therapeutic decisions.

1. LVADs have emerged as destination therapy for advanced heart failure, however, these are still limited by many potential complications after implant, such as right heart failure, aortic regurgitation, thrombosis, infections 2. A seriate and accurate echocardiographic evaluation is needed in LVAD carriers but may sometimes be challenging, due to artifacts or poor acoustic windows due to the device 3. Left ventricular unloading is the main feature to consider to evaluate and adjust device function and requires many echocardiographic parameters to be assessed 4. Ramp test during echocardiography may be of additional value to optimize device speed and to early identify pump dysfunction.

AIMS:Left ventricular reverse remodelling (LVRR) is a prognostic marker in patients with dilated (DCM) and non-dilated left ventricular cardiomyopathy (NDLVC). The utility of combining late gadolinium enhancement (LGE) and genetic testing in predicting LVRR in DCM/NDLVC remains a knowledge gap. This study aimed to assess an integrated approach including LGE data and genetics to predict LVRR in DCM/NDLVC patients. METHODS AND RESULTS:This multicentre observational study included DCM/NDLVC patients with: (i) baseline echocardiographic left ventricular ejection fraction (LVEF) <50%; (ii) genetic testing; (iii) baseline cardiac magnetic resonance (CMR); (iv) 12-month follow-up echocardiographic data. LVRR was defined as LVEF increase ≥10% or LVEF ≥50% (if baseline LVEF <45%) at 12 months. Outcome measures were: (i) all-cause mortality, heart transplant, or left ventricular assist device implantation (D/HT/LVAD); (ii) sudden cardiac death or major ventricular arrhythmias (SCD/MVA). Arrhythmogenic genes studied were LMNA, DSP, FLNC, and RBM20. Among 1757 DCM/NDLVC with genetic data, 616 met eligibility (462 DCM, 154 NDLVC; age 51 ± 14 years, 34% female). LVRR occurred in 314 patients (51%): 251 (54%) in DCM and 63 (41%) in NDLVC (p = 0.004). Independent predictors of LVRR within 1 year included titin truncating variants, absence of arrhythmogenic genes, and absence of LGE ring-like pattern. In patients with LVEF <35%, only the presence of LGE ring-like pattern and arrhythmogenic genes remained independently related to a lower rate of LVRR and increased SCD/MVA risk. CONCLUSION:In a large genetically and CMR characterized DCM/NDLVC cohort, arrhythmogenic genotypes and LGE ring-like pattern were inversely related to LVRR, particularly in patients with LVEF <35%.

INTRODUCTION:Maximal effort, defined by a respiratory exchange ratio (RER) ≥ 1.10, is crucial for accurate interpretation of cardiopulmonary exercise testing (CPET). Standard tests rely on non-metabolic thresholds, such as peak predicted heart rate (ppHR) ≥ 85 %, double product (DP) ≥ 20,000 bpm*mmHg and peak metabolic equivalent of task (MET) ≥ 5.0. This study aimed to assess the effectiveness of non-metabolic thresholds in detecting maximal effort, compared with the RER ≥ 1.10 criterion. METHODS:We retrospectively analyzed stable patients who underwent CPET from 2022 to 2023, regardless of test indication, history of heart failure (HF), or medication use. All patients also performed transthoracic echocardiography. RESULTS:Among 239 middle-aged patients (53 ± 14 years, 67 % male), 86 % achieved a RER ≥ 1.10, and 65 % had a diagnosis of HF. Non-metabolic thresholds correctly identified maximal efforts (RER ≥ 1.10) in 75 % of the cases (AUC < 0.600). Misclassified cases were more likely to have a history of atrial fibrillation (AF), paced rhythm, HF, and beta-blockers or RAAS inhibitors use. These patients exhibited lower VO2 peak and higher VE/VCO2 slope. Multivariable analysis identified HF history (OR 4.8, CI 95 % 1.6-15.6, p: 0.005), low resting DP (≤ 7500 mmHg*bpm), and ramp protocol as independent predictors of discordant tests. CONCLUSION:Non-metabolic thresholds misclassified up to 25 % of tests with RER ≥ 1.10 as non-maximal, potentially leading to inaccurate interpretation. In patients with HF, poor expected functional capacity and low DP, direct referral to CPET-equipped facilities may provide more accurate assessment than relying on non-metabolic thresholds.

Septic cardiomyopathy (SCM) is an acute, reversible myocardial dysfunction occurring in the context of sepsis, independent of ischemic heart disease. Despite its frequent occurrence in critically ill patients, SCM remains poorly defined and underdiagnosed. This article provides clinicians with a practical guide for the recognition and management of SCM, with particular attention to the role of bedside echocardiography. Echocardiography is emphasized as both a diagnostic and hemodynamic monitoring tool to optimize treatment strategies in patients with sepsis and septic shock. Advanced techniques such as speckle-tracking echocardiography enhance sensitivity for detecting subclinical myocardial impairment and support differential diagnosis. Real-time echocardiographic assessment allows tailored therapy and may improve patient outcomes. Key elements include the recognition of characteristic echocardiographic patterns, integration of global longitudinal strain analysis, and the use of echocardiographic findings to guide hemodynamic management decisions.

The first European Society of Cardiology (ESC) guidelines on the management of cardiomyopathies (CMPs), published 1 year ago, remain highly relevant. These guidelines provide a comprehensive framework to manage the complexity of CMPs, consolidating previous approaches. All CMPs are now addressed systematically in one document. The ESC recommends a 'CMP-oriented' approach, emphasizing thorough clinical assessments and phenotype-first categorization into hypertrophic, dilated, arrhythmogenic, restrictive, and non-dilated left ventricular CMP. Despite the utility of this method, certain classifications, such as arrhythmogenic right ventricular CMP and the novel non-dilated left ventricular CMP, raise controversies. Key advances in the guidelines include the use of genetic testing and cardiac magnetic resonance imaging to refine diagnoses and inform treatment, especially for high-risk genotypes. These guidelines advocate for personalized, multidisciplinary care. Overall, they represent a significant step forward but highlight the evolving nature of CMP management as scientific understanding progresses.

Background and Objectives: The introduction of portable ultrasound devices has transformed clinical practice in emergency medicine. Diagnostic accuracy and patient safety have been enhanced by point-of-care ultrasonography (POCUS), which has become a fundamental diagnostic and procedural tool. In addition to the standard clinical evaluation, POCUS provides quick patient assessments, allowing for the exclusion of life-threatening conditions and prognostication in different critical situations. Tissue Doppler imaging (TDI), as an advanced echocardiographic technique, offers additional quantitative data by measuring myocardial velocities, thereby improving the evaluation of systolic and diastolic ventricular function. The purpose of this review is to highlight the potential use of TDI in multiple acute and critical conditions. Materials and Methods: We conducted a narrative review of the main application topics for TDI. Results: TDI is an essential diagnostic and prognostic tool for acute coronary syndromes, assessing systolic or diastolic dysfunction, and etiological diagnosis of acute heart failure. It helps differentiate cardiogenic pulmonary edema from acute respiratory distress syndrome and identifies right ventricular systolic dysfunction in acute pulmonary embolism. TDI also facilitates distinctions between hypertension emergencies and urgencies and contributes to the stratification of atrial fibrillation reoccurrence risk. Furthermore, it aids in the differentiation of constrictive pericarditis from other restrictive cardiomyopathy patterns. In intensive care settings, TDI is particularly valuable during mechanical ventilation weaning, where elevated E/E' values serve as a predictor of weaning failure. Due to its accessibility, rapid execution, and high reproducibility, it is suitable for longitudinal monitoring. Conclusions: TDI enhances the diagnostic precision, guides therapeutic strategies, and provides critical prognostic insights across a wide range of time-sensitive clinical scenarios, solidifying its role as an indispensable tool in modern emergency and critical care practice.

Cardiac adipose tissue is normally present in the epicardium, but a variable amount can also be present in the myocardium, particularly in the subepicardial regions of the right ventricular anterolateral and apical regions. Pathological adipose tissue changes may occur in both ischemic (previous myocardial infarction) and nonischemic (previous myocarditis, arrhythmogenic cardiomyopathy, lipomatous hypertrophy of the interatrial septum, cardiac lipomas and liposarcomas) conditions, with or without extensive replacement-type myocardial fibrosis. Cardiac magnetic resonance is the gold standard imaging technique to characterize myocardial tissue changes and to distinguish between physiological and pathological cardiac fat deposits. In this review, we present the most common conditions presenting with myocardial fatty infiltration or with fatty replacement and the best magnetic resonance sequences to detect them, providing a comparison with histological findings and discussing their clinical significance.

Arrhythmogenic cardiomyopathy (ACM) is a cardiac disorder characterized by structural alterations of the myocardium, which predisposes individuals to ventricular arrhythmias and increases the risk of sudden cardiac death. Initially described as arrhythmogenic right ventricular cardiomyopathy, the involvement of the left ventricle (LV) has been subsequently recognized, leading to the classification of various phenotypes under LV non-dilated cardiomyopathy. The clinical spectrum of ACM ranges from life-threatening ventricular arrhythmias to overt heart failure, sometimes presenting with acute myocarditis-like episodes and extracardiac symptoms, further contributing to the disease's heterogeneity. Diagnosis relies on imaging modalities, such as echocardiogram and cardiac magnetic resonance imaging, to detect areas of fibro-fatty replacement and/or non-ischemic ventricular scarring, integrated with genetic analysis. The 2023 European Society of Cardiology guidelines on Cardiomyopathies underscore the importance of a comprehensive diagnostic approach, combining imaging and genetics for arrhythmic risk stratification and comprehensive patient management. Growing evidence on genotype-phenotype correlation, along with the validation of specific predictive scores, is improving ACM clinical management and promoting personalized treatment tailored to individual and familial characteristics.

The interventional echocardiographer (IE) plays a crucial role in structural heart interventions, yet faces significant risks from ionizing radiation, often greater than those encountered by the primary interventional cardiologist (IC). This elevated exposure is due to the IE's close proximity to the patient's head and, consequently, to the X-ray source, combined with a general lack of dedicated protective equipment designed for their position. Despite growing awareness of radiation safety in the catheterization lab, the specific protection needs of IEs remain under-recognized. Recent studies have shown that IEs can receive up to 11 times more radiation than ICs during procedures guided by transesophageal echocardiography (TEE), such as transcatheter edge-to-edge repair or left atrial appendage closure. These findings, together with the recent reduction in recommended dose thresholds for deterministic effects like cataract formation, emphasize the urgent need to implement effective protective measures. Radiation exposure can be significantly reduced by following the core principles of radiation safety: time, distance, and shielding. Key strategies include optimizing the IE's position based on expected fluoroscopic projections, using dedicated mobile or ceiling-mounted shields, adopting lightweight personal protective equipment, and encouraging the use of low-dose imaging protocols. Ongoing education and training, targeted not only at IEs but also at ICs, is essential to reinforce safe practices and promote a culture of radiation awareness. Technological innovations offer promising solutions. New shielding systems like the Eggnest® and Rampart® have demonstrated effective protection for staff near the patient's head. Disposable radiation-reducing drapes and the development of robotic systems for remote TEE manipulation may further enhance safety without compromising workflow or image quality. Advances in imaging hardware and software also support dose reduction without sacrificing clinical effectiveness. Finally, computational dosimetry methods may soon allow for more accurate and individualized exposure monitoring, overcoming the limitations of conventional dosimeters. In summary, improving radiation protection for IE must become a priority. A combination of strategies is necessary to ensure long-term safety and sustainability in this rapidly evolving field.

Previous studies demonstrated that integrase-strand-transfer-inhibitors (INSTIs) promote adipocyte differentiation, while nucleoside-reverse-transcriptase-inhibitors (NRTIs) tenofovir-alafenamide-fumarate (TAF) and tenofovir-disoproxil-fumarate (TDF), inhibit adipogenesis. NRTIs were shown to counteract the pro-adipogenic effects of INSTIs[6]. However, the effects of non-nucleoside-reverse-transcriptase-inhibitors (NNRTIs) and of the novel long-acting INSTI cabotegravir (CAB), on adipogenesis, alone or in combination with NRTIs or other INSTIs, remain unclear. This study aims to elucidate the impact of NNRTIs and recent INSTIs on adipogenesis. 3T3-L1 cells were used as an adipogenesis in vitro model. The NNRTIs doravirine (DOR) and rilpivirine (RPV) were tested alone and in combination with DTG, CAB, TDF, TAF. Adipogenesis was assessed by Oil-Red-O-staining and by measuring expression-levels of peroxisome-proliferator-activated-receptor-gamma (PPARγ) and CCAAT/enhancer-binding-protein-alpha (C/EBPα). Moreover, Fibroblast-marker ER-TR7 was assessed by immunohistochemistry. CAB, DOR, and RPV promoted adipogenesis, with CAB and DOR showing greater effects. In combination, NNRTIs enhanced the adipogenic effects of CAB and DTG. Conversely, TAF and TDF, when paired with RPV or DOR, inhibited adipogenesis. NNRTIs and CAB increased ER-TR7 expression, suggesting fibroblastic differentiation. Finally, NNRTIs and INSTIs promote adipogenesis and induce fibroblastic features in 3T3-L1 cells. Contrarily, TAF and TDF exhibited an antagonistic effect on adipogenesis when combined with certain antiretrovirals, supporting our previous research.

AIMS:Arrhythmic risk stratification in patients with non-ischaemic dilated cardiomyopathy (DCM) remains challenging. The LGE-dispersion mapping is a novel method for the quantification of tissue heterogeneity through the Global Dispersion Score (GDS). We sought to evaluate the usefulness of GDS in arrhythmic risk stratification of DCM patients. METHODS AND RESULTS:Consecutive non-ischaemic DCM patients underwent cardiac magnetic resonance imaging. GDS was calculated in LGE images. During a follow-up of 3.3 years (2 to 6 years), the combined endpoint of sudden cardiac death and appropriate implantable cardioverter-defibrillator intervention was considered. The final population included 510 patients (mean age was 56 ± 15 years). Left ventricular ejection fraction (LVEF) was >35% in 241 patients (47%). LGE was present in 225 patients (45%). Median extent of LGE was 12% of LV mass [interquartile range (IQR) 6-20%]. Among patients with positive LGE, GDS was 0.14 (IQR 0.08-0.20). During follow-up 81 patients had malignant ventricular arrhythmias (8 SCD, 73 appropriate ICD interventions). At Kaplan-Meier analysis, patients with GDS > 0.10 had worse prognosis than those with lower values of GDS (P < 0.0001). At multivariate analysis, GDS > 0.10 (HR 2.9, 95% CI: 1.7-5, P = 0.0002) was an independent predictor of events. The prognostic value of GDS was confirmed in subgroups of patients with LVEF ≤ 35% and >35%. CONCLUSION:GDS is a useful marker to identify DCM patients at higher risk for malignant arrhythmic events regardless of LVEF and extent of LGE.

Background/Objectives: Exercise training (ET) can improve wound healing and prevent the recurrence of skin lesions. Aerobic ET stimulates the NAD+-dependent deacetylase sirtuin 1 (SIRT1). The beneficial effects of ET and SIRT1 activation in wound healing have been characterized when considered separately. This study aimed to investigate the potential role of SIRT1 as a mediator of the effects of sera isolated from athletes who regularly participate in aerobic ET (middle-distance running, MDR) on cells primarily involved in wound healing. Methods: Human keratinocytes, fibroblasts and endothelial cells were conditioned with sera from middle-distance runners and age-matched sedentary subjects (sed). Cell motility, angiogenesis and the expression of key biomarkers of cell activation were evaluated in the presence or absence of the selective SIRT1 inhibitor EX-527. Results: Higher SIRT1 activity was detected in all of the cell lines conditioned with the MDR group sera compared with that in the cells in the sed group sera. The involvement of SIRT1 was demonstrated by EX-527’s selective inhibition. Alongside the increase in SIRT1 activity, a marked increase in migration, invasion and angiogenesis was observed. The levels of E-cadherin decreased while those of integrin β1 and vinculin increased in the keratinocytes and fibroblasts conditioned with the MDR group sera compared to these values with the sed group sera, respectively. Increased levels of differentiation markers, such as involucrin in the keratinocytes, FAP1α in the fibroblasts and CD31 in the endothelial cells, were observed with the MDR group sera compared to these values using the sed group sera. Conclusions: The ex vivo/in vitro approach used here links aerobic ET-induced SIRT1 activity to proper tissue regeneration.

Fabry disease or Anderson-Fabry disease is an X-linked lysosomal storage disorder caused by a deficiency of α-galactosidase A (GLA), leading to systemic accumulation of globotriaosyl-ceramide (Gb3). Initially described in 1898 as a dermatological condition, Fabry disease is now recognized as a progressive multisystem disorder with significant cardiac involvement. Cardiomyopathy in Fabry disease arises from Gb3 accumulation in cardiac tissue, resulting in fibrosis, left ventricular hypertrophy (LVH), diastolic dysfunction, and heart failure. The deacylated derivative, lysoGb3, serves as a biomarker of cardiac involvement. Diagnosis relies on enzyme assays, genetic testing, and advanced cardiac imaging modalities like echocardiography and cardiac MRI. Management strategies are centered around enzyme replacement therapy, and prognosis varies due to phenotypic heterogeneity and severity of disease progression. Psychological and social burdens further complicate patient care. However, underdiagnosis remains a concerning issue, particularly in individuals with unexplained cardiomyopathies. Early recognition through increased clinical awareness and genetic screening is crucial for timely intervention. Ongoing research is essential to develop new therapies targeting the genetic and metabolic roots of the disease. This systematic review comprehensively examines current evidence regarding the mechanisms, diagnosis, treatment, and prognosis of cardiomyopathy associated with Fabry disease, providing insights that may enhance clinical practice and guide future research initiatives.

AIMS:To assess the prognostic value of LL criteria in AM. METHODS:257 consecutive hemodynamically stable patients fulfilling updated LL criteria for diagnosis of clinically suspected AM (presenting with chest pain, troponin raise and no obstructive coronary artery) were enrolled. CMR imaging was performed using 1.5-T scanners following Updated LL criteria. Patients were divided into two groups accordingly to the combination of LL criteria: those with AM diagnosis made using the "original" LL Criteria (DOC), who exhibited both myocardial edema on T2-STIR images and non-ischemic late gadolinium enhancement (LGE), and those in whom diagnosis requiring at least one "mapping" Criteria (DMC) group, where the diagnosis was made either solely on the basis of mapping criteria (T2 + T1 and/or ECV) or by combination of only one original plus ≥1 mapping criterion. Cardiac death, resuscitated cardiac arrest, appropriate implantable cardioverter-defibrillator (ICD) shock, heart failure hospitalization and myocarditis recurrence were considered as cardiac events during the follow-up. RESULTS:Final population included 210 patients. During a median follow-up of 57 months, cardiac events were recorded in 31 patients, all of them occurred in the DOC group and none in DMC group. The Kaplan-Meier curves analysis showed that DOC group (p < 0.0001), LGE presence (particularly if midwall-septal/ring-like pattern, p < 0.0001) and a higher number of LL criteria (p = 0.0002) were associated with worse prognosis. At multivariate analysis the number of LL criteria, DOC and midwall septal/ring-like LGE pattern were confirmed to be independent predictors of major cardiac events. CONCLUSIONS:In patients with hemodynamically stable AM, conventional LL criteria including edema at T2-STIR and positive LGE provide significant prognostic information, while mapping criteria had a limited role.