Hongqi Shenmai Yin attenuates adverse cardiac remodeling following myocardial infarction via inhibition of STING-dependent PANoptosis.

A machine learning approach using echocardiographic and hematological parameters to classify cerebral small vessel disease burden.

Isolated T-Wave Inversion in Lead aVL: A Diagnostic Blind Spot in Emergency Department Chest Pain Evaluation.

Cardio-oncology has emerged as a pivotal discipline aimed at preserving cardiovascular health in patients undergoing contemporary cancer therapies. Despite growing awareness of treatment-related cardiac injury, the evidence base supporting preventive strategies and standardized safety assessment remains fragmented. This review critically appraises randomized controlled trials evaluating pharmacological and non-pharmacological interventions for the prevention of cancer therapy-related cardiac dysfunction. In parallel, we examine how cardiovascular events are monitored, defined, and reported in major oncology trials, with particular emphasis on patient selection criteria and the use of structured surveillance protocols. Across drug classes repurposed from heart failure (HF) prevention and treatment, including neurohormonal antagonists, angiotensin receptor-neprilysin inhibition, lipid-lowering therapies, as well as exercise-based interventions, randomized evidence has demonstrated modest and inconsistent benefits. Reported effects are largely confined to subclinical alterations, such as changes in left ventricular systolic function, myocardial deformation parameters, or circulating cardiac biomarkers. By contrast, convincing reductions in clinically meaningful outcomes, including overt HF, treatment interruption, or cardiovascular mortality, remain limited. Concurrently, oncology trials frequently exhibit heterogeneous cardiovascular event definitions, incomplete safety reporting, and systematic exclusion of patients with pre-existing cardiac disease, thereby constraining external validity and obscuring the true burden of cardiotoxicity and competing cardiovascular risks. Advancing the field will require a paradigm shift toward individualized, risk-enriched prevention strategies anchored in clinically relevant endpoints. Broader inclusion of patients with stable cardiovascular comorbidities, managed under structured specialist supervision, alongside standardized frameworks for cardiovascular safety monitoring and reporting, is essential. Emerging artificial intelligence, as enabled tools applied to cardiac imaging, electrocardiography, and remote monitoring offer a promising opportunity to harmonize early detection of cardiotoxicity across trial sites and refine phenotyping of treatment-related cardiac injury. Integrating these elements into future trial design will be critical to ensure that therapeutic progress in oncology is not undermined by preventable cardiovascular harm.

The aim of this study was to compare preoperative right ventricle-to-left ventricle (RV/LV) ratios by computed tomography angiography (CTA) and echocardiography and evaluate treatment outcomes of ultrasound-assisted catheter-directed thrombolysis (USAT) or mechanical thrombectomy (MT) in patients with intermediate-risk pulmonary embolism (PE). We retrospectively identified patients treated for intermediate-risk PE from 2018 to 2023 defined by systolic blood pressure (BP) >90 mmHg and right ventricle dysfunction defined by RV/LV ratio >0.9 via echocardiogram. RV/LV ratios were also evaluated on diagnostic CTA for comparison to echocardiogram values. Patients underwent USAT or MT based on thrombus location and contraindications to thrombolysis. Primary outcomes were intensive care unit (ICU) length of stay (LOS), hospital LOS, and 30-day and 1-year survival. Secondary outcomes included RV/LV change post-treatment on echocardiography, concomitant deep vein thrombosis (DVT), elevated cardiac biomarkers, blood transfusion, history of DVT/PE or malignancy, and imaging modality comparison in determination of RV/LV and RV/LV changes. Of 120 patients from a single center treated for intermediate-risk PE, 100 underwent USAT and 20 MT. There was no difference in ICU LOS (2.4 vs 2.6 days; P = .67) or hospital LOS (4.8 vs 5.7 days; P = .41) for USAT and MT, respectively. There was no difference in 30-day (98% vs 100%), or 1-year survival (96% vs 90%). MT patients had greater incidence of blood transfusion (25% vs 5%; P = .011). CTA overestimated RV/LV ratios preoperatively compared with echocardiography (1.4; SD, 0.4 vs 1.3; SD, 0.2; P = .027). Patients undergoing MT were more likely to have identified lower extremity DVT compared with patients undergoing USAT (90% vs 65%; P = .033). Other secondary outcomes showed no significant differences between treatment groups. Both USAT and MT provide excellent short-term and intermediate outcomes in patients with intermediate-risk PE, similar survival rates, similar post-treatment change in right heart dysfunction, and comparable ICU and hospital stays. MT is associated with higher transfusion rates, so caution should be exercised in patients felt to be at risk from further blood loss. These findings support individualized, anatomy- and risk-based selection of catheter-based therapy within a multidisciplinary PE response framework.

Preliminary comparative evaluation of an immunofluorescence point-of-care system and central laboratory platforms for measuring cardiac biomarkers.

This study aimed to determine the prognostic value of baseline serum cardiac biomarkers measured at emergency department admission in patients with acute ischemic stroke undergoing reperfusion therapy. This retrospective cohort study evaluated data from 433 AIS patients treated with intravenous thrombolysis (IVT), mechanical thrombectomy (MT), or combined therapy. Serum lactate dehydrogenase, creatine kinase, plasma N-terminal pro-brain natriuretic peptide, and high-sensitivity cardiac troponin T levels were analyzed. Stroke severity, functional outcomes, hemorrhagic transformation, and mortality were assessed. Continuous variables were evaluated using the Shapiro-Wilk test, Kruskal-Wallis ANOVA, and post-hoc pairwise comparisons. Diagnostic efficacy was calculated using ROC-AUC and the Youden Index. Independent risk factors were identified via Multivariate Logistic Regression analysis. High-sensitivity cTnT predicted functional prognosis at both discharge and 3 months, whereas LDH predicted outcomes exclusively at 3 months. Elevated CK and LDH levels correlated significantly with stroke etiology. An hs-cTnT value > 10.5 pg/mL independently increased the risk of poor discharge prognosis (OR: 1.725, p < 0.05). In multivariate logistic regression, age, baseline NIHSS, and hs-cTnT were independent risk factors for poor discharge outcomes. For 3-month mRS scores, the optimal prognostic cut-off values were > 200 U/L for LDH (p = 0.003) and >10.5 pg/mL for hs-cTnT (p = 0.007). In the final multivariate model, baseline NIHSS, stroke etiology, LDH (>200 U/L, OR: 1.845, p < 0.05), and hs-cTnT (>10.5 pg/mL, OR: 1.685, p < 0.05) emerged as independent risk factors for a poor 3-month prognosis. Integrating admission cardiac biomarkers into clinical evaluation scores significantly enhances risk stratification and predictive accuracy in acute ischemic stroke management.

Oxidative stress and inflammation, in particular, are crucial factors in the pathogenesis of myocardial infarction (MI). Isoproterenol (ISO) is frequently preferred for creating experimental MI models because it reflects the pathophysiology of MI in humans. ThepurposeofthisstudywastoidentifypotentialalterationsinOTULINandprogranulin(PRGN)levelsatvariousstagesduringandfollowingcardiacremodelinginexperimentalMIcausedbyISO. The study consisted of control groups and ISO groups (ISO-6-h, ISO-24-h, ISO-3-day, and ISO-7-day) representing important time points in experimental MI and subsequent cardiac remodeling. The experimental MI model induced by ISO was validated by increased serum cardiac markers and histopathological changes in the heart tissue. Furthermore, it was determined that oxidative stress and inflammation, important factors in MI pathophysiology, emerged in the heart tissue after ISO administration. However, in the ISO-7-day group, a significant reduction in oxidative stress and inflammation was observed along with cardiac remodeling. In the experimental MI model, a time-dependent decrease in cardiac OTULIN levels was observed, while conversely, an increase in cardiac PRGN levels was detected. These time-dependent dynamic changes in cardiac OTULIN and PRGN suggest that both may play a role in processes related to MI and cardiac remodeling. In conclusion, endogenous OTULIN and PRGN may be associated with oxidative stress and inflammation in cardiac remodeling during and after experimental MI. This reveals the potential of OTULIN and PRGN as cardiac biomarkers in MI prognosis and suggests they could also be molecular targets for therapeutic strategies.

Treatment of sarcoma includes high-dose anthracyclines, which can cause cardiotoxicity. This study assesses the correlation of cardiac biomarkers and echocardiographic parameters on asymptomatic cardiotoxicity in sarcoma patients treated with anthracyclines. Consecutive patients diagnosed with sarcoma and treated with anthracyclines were included in this retrospective cohort study using registry data. Echocardiography was performed before start of anthracycline chemotherapy (baseline), after completing treatment (short-term follow-up), and 6-12 months after termination of treatment (long-term follow-up). The primary endpoint was the occurrence of asymptomatic cardiotoxicity at short-term follow-up. We included 44 patients (29.6% female) with a median age of 28.9 [22.2-38.7] years. Baseline left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS) decreased significantly from 58.4% ± 5.0% to 54.2% ± 9.3% (p = 0.013) and -19.1% ± 2.2% to -17.2% ± 3.5% at short-term follow-up (p = 0.002), respectively. After Cycle 1, 86.5% of the patients showed NT-proBNP ≥ 125 ng/L compared to 3.9% at baseline (p < 0.001), and after completion of therapy, 65.5% had elevated cardiac Troponin T (cTnT) ≥ 14 ng/L compared to 11.5% at baseline (p = 0.003). Asymptomatic cardiotoxicity was observed in 30 patients (68.2%). Mean follow-up was 2.4 [1.5-2.9] years. cTnT ≥ 14 ng/L after Cycle 4 was associated with cardiotoxicity (HR: 3.75 [1.28-11.0], p = 0.016), and NT-proBNP per 100 units increase after Cycle 1 was associated with an increased risk of mortality (HR: 1.36 [1.004-1.85], p = 0.047). Sarcoma patients treated with high-dose anthracyclines are at increased risk of developing cardiac dysfunction as assessed by LVEF and GLS. cTnT and NT-proBNP levels increase significantly during treatment and can be valuable markers to improve the risk stratification of patients treated with high-dose anthracyclines.

Prevalence and characterization of normotensive shock in intermediate-high risk acute pulmonary embolism patients

ABSTRACT Background Dynamic changes in inflammatory and cardiac biomarkers following acute ischemic stroke may better reflect the underlying pathophysiological response than static measurements. However, their prognostic significance after successful mechanical thrombectomy remains unclear. Methods The study was designed as a retrospective cohort study and included 48 patients with large vessel occlusion who underwent successful endovascular recanalization (TICI 2b–3) treatment at a tertiary stroke center and were dynamically monitored with troponin and complete blood count tests. NLR and hs-cTnI (ng/L) values were evaluated before the procedure and repeated 16–24 hours later. Results In the first regression model, unfavorable (mRS 3–6) outcome, age and NLR at 16–24 h showed results close to statistical significance (p = .056 and .061, respectively) and the model was found to be significant (p < .001, Nagelkerke R2: 0.567, AUC = 0.883). In the second regression model, which evaluated functional dependency or mortality (mRS: 4–6) NLR at 16–24 h were found to be significantly predictive (p = .041), and the model was evaluated as significant (p < .001, Nagelkerke R2 = 0.613 and AUC = 0.924). ΔNLR was found to be positively and significantly associated with mRS 4–6, and Δ hs-cTnI was found to be positively and significantly associated with both mRS 4–6 and mRS 6 (p < .05). Conclusion Early dynamic increases ΔNLR and Δ hs-cTnI were significantly tied to functional dependence and mortality only in unadjusted analyses. Due to sample size limitations and multicollinearity, the independent prognostic value of these dynamic shifts remains exploratory and requires validation in larger and adjusted cohorts.

Radiation-induced heart disease (RIHD) remains aclinically significant consequence of thoracic radiotherapy (RT). Historically, the mean heart dose (MHD) has served as the primary metric for cardiac risk estimation. However, accumulating evidence demonstrates that MHD inadequately captures the heterogeneous dose distribution across functionally distinct cardiac substructures and poorly predicts specific cardiovascular endpoints. This narrative review synthesizes recent evidence (2013-2025) on the transition from whole-heart dosimetry to substructure-level dose-volume analysis in thoracic RT, encompassing dose-response relationships for specific cardiac substructures, advances in artificial intelligence (AI)-driven auto-segmentation, modern cardiac-sparing delivery techniques, biomarker-guided surveillance, pharmacologic cardioprotection, and normal tissue complication probability (NTCP) modeling. Astructured literature search was conducted across PubMed, Scopus, and Web of Science databases (January 2013-March 2025) using predefined search terms. Studies reporting cardiac substructure dose-response relationships, auto-segmentation performance, cardiac-sparing techniques, biomarkers, pharmacologic interventions, and NTCP models were included. Substructure-specific dose metrics-particularly dose to the left anterior descending artery (LAD), heart base, left ventricle (LV), and cardiac conduction system-predict coronary events, arrhythmias, and overall survival with substantially greater accuracy than MHD. Deep learning auto-segmentation now achieves ≥ 94% clinical acceptability for cardiac chambers, enabling routine substructure-based planning. Deep inspiration breath hold (DIBH) reduces heart and LAD doses by 36-42%, and proton beam therapy (PBT) offers superior cardiac sparing across all tumor sites, though randomized cardiac outcome data remain pending. Statins demonstrate acompelling retrospective cardioprotective signal (up to 66% reduction in major adverse cardiac events), but prospective validation is lacking. The 2022 European Society of Cardiology (ESC) cardio-oncology guidelines and the 2024 American Radium Society (ARS) appropriate use criteria provide the current clinical framework. The paradigm shift from MHD to substructure-level cardiac dosimetry represents atransformative advance in thoracic RT. Integration of AI-driven segmentation, advanced delivery techniques, biomarker surveillance, and pharmacologic cardioprotection into routine clinical workflows is essential for precision cardiac risk mitigation in irradiated patients.

BackgroundTraditional diagnostic criteria for hypoxic-ischemic encephalopathy (HIE) rely heavily on documented fetal acidemia, which may be missing or unavailable in resource-limited settings. This study evaluated the diagnostic utility of multi-organ biomarkers in identifying neonates with HIE who do not meet classic acidemic criteria ("non-classic HIE").MethodsThis clinical population study analyzed 416 full-term and late-preterm neonates over 3years at a tertiary neonatal intensive care unit (NICU). Participants were categorized into "classic HIE" (acidemia present) and "non-classic HIE" (no acidemia but presenting with clinical encephalopathy). Cardiac (Troponin-I), renal (urea/creatinine), hepatic (ALT/AST), and hematological (neutrophil-to-lymphocyte ratio [NLR]) biomarkers were evaluated to predict HIE severity and short-term outcomes.ResultsOf the cohort, 54.8% (n = 228) were classified into the non-classic HIE group. Within this group, 49.1% presented with mild, 43.4% with moderate, and 7.5% with severe clinical features, confirming systemic hypoxia despite "normal or near-normal" initial blood gases. Significant elevations in cardiac Troponin-I and AST were observed in the mild-to-severe classic HIE groups compared to the non-classic cohort (p < 0.001). Troponin-I showed high performance (AUC = 0.711) in predicting moderate-to-severe HIE across both cohorts. The NLR was significantly higher in all infants with clinical evidence of moderate-to-severe hypoxic insult.ConclusionsMulti-organ biomarkers, particularly Troponin-I and NLR, offer valuable adjunctive metrics reflecting the severity of systemic hypoxic insults. They assist in identifying asphyxiated neonates when early blood gases are inconsistently captured or fail to show fetal acidemia.

Current approaches for preoperative cardiovascular risk prediction remain suboptimal. CT-derived body composition metrics may provide objective markers of cardiometabolic health, yet their predictive value for postoperative cardiovascular events remains unclear. We included patients with cardiovascular disease or risk factors undergoing major noncardiac surgery in the prospective, multicenter PREVENGE-CB (PREdiction of Vascular Events after Noncardiac surGEry with Cardiac Biomarkers) cohort and its Nanfang extension. Preoperative abdominal CT scans were analyzed to quantify the area and radiodensity of skeletal muscle and adipose tissues at the third lumbar vertebral level. The primary outcome was composite cardiovascular events within 30 days after surgery. We used logistic regression models to evaluate the added predictive value of body composition metrics beyond guideline-recommended predictors. In the Nanfang cohort, the optimal subset of body composition metrics was selected by minimizing the Akaike Information Criterion for the primary outcome. Nested models were compared using measures of model fit, discrimination, risk reclassification, and net benefit. The findings were validated in the PREVENGE-CB cohort. Among 1594 patients, 211 (13.2%) had the primary outcome. Larger skeletal muscle and adipose areas were generally associated with lower risk, whereas higher adipose radiodensity and lower muscle radiodensity indicated higher risk. In the Nanfang cohort, an optimal subset of three body composition metrics-skeletal muscle area, muscle radiodensity and subcutaneous fat radiodensity-improved discrimination of the primary outcome over the Revised Cardiac Risk Index (increase in area under the curve [ΔAUC] = 0.136; 95% CI, 0.083 to 0.188), the Gupta Myocardial Infarction and Cardiac Arrest risk calculator (ΔAUC = 0.032; -0.002 to 0.065), and a refitted clinical model (ΔAUC = 0.035; 0.008 to 0.062). These findings were validated in the PREVENGE-CB cohort. CT-derived body composition metrics improved prediction of postoperative cardiovascular events beyond conventional clinical predictors.

Dysautonomia in idiopathic inflammatory myopathies (IIM) is an underrecognized and poorly characterized manifestation, despite its potential implications for disease prognosis and clinical management. In this study, we assessed autonomic dysfunction in patients with IIM and investigated its correlation with cardiac imaging biomarkers based on cardiac magnetic resonance imaging (CMRI). The study recruited clinically suspected IIM patients aged 10-60 years and age- and sex-matched healthy controls. Evaluations included myositis disease activity assessment tool (MDAAT), autonomic function testing (AFT), tilt table test (TTT), and CMRI with multiparametric mapping. Among 31 diagnosed cases of IIM, 28 patients underwent AFT and TTT. Of these, 12 had dermatomyositis, 7 had overlap myositis, 7 had immune-mediated necrotizing myopathy, and 2 had anti-synthetase syndrome. The mean age of onset was 33±12.92 years, with an average illness duration of 16.63±19.43 months, and a female predominance (F:M = 2.1:1). The patients exhibited a lower median total autonomic power (563.2, interquartile range [IQR] = 209.6-1964.6 vs 1606.5, IQR = 1048.6-2676; P = 0.003). The TTT was positive in 10.9% cases. The mean standard deviation of normal-to-normal intervals (SDNN) was lower among the patients (31.7 ± 22.3 vs 43.4 ± 13.7; P = 0.023). SDNN and total autonomic power were negatively correlated with native-T1-mapping (ρ = -0.537, P = 0.009; ρ = -0.638, P = 0.007). An SDNN cut-off of ≤28.68 had a sensitivity of 83.3% and specificity of 76.0% (area under the curve [AUC] = 0.773, P = 0.030), whereas a total power of ≤725.81 had a sensitivity of 83.3% and specificity of 74.0% (AUC = 0.760, P = 0.039) in diagnosing cardiac involvement in IIM. In this first-of-its-kind study integrating AFT and TTT with CMR to evaluate IIM, patients demonstrated significant autonomic dysfunction, with AFT parameters showing a correlation with CMR findings, thus indicating their potential as a simple predictor of cardiac involvement.

The role of autologous stem cell transplantation (ASCT) is central in AL amyloidosis and continues to be defined in the era of newer therapies. To evaluate contemporary patient selection, practice patterns, and outcomes, we conducted a retrospective, multicenter study across nine tertiary referral centers, including 1047 patients with AL amyloidosis who underwent ASCT between 2010 and 2020. Most patients (67.9%) received full-dose melphalan conditioning, and 66.5% received pre-ASCT induction therapy, predominantly proteasome inhibitor-based regimens. Day-100 all-cause mortality was 3.0%, representing a substantial improvement compared with historical cohorts. Post-ASCT hematological responses were satisfactory in 75.4% of patients. Among patients with paired assessments, ASCT deepened responses in 56.3% who had not achieved a complete response with induction therapy. With a median follow-up of 5.1 years, the median overall survival was 6.3 years. Independent predictors of inferior survival included age ≥60 years, bone marrow plasma cells ≥20%, pre-ASCT dFLC ≥40 mg/L, elevated cardiac biomarkers, lambda-restricted disease, reduced eGFRand reduced-dose conditioning. In this contemporary cohort, ASCT for AL amyloidosis demonstrated low early mortality, high rates of deep hematologic response, and durable survival in carefully selected patients. These findings support its role as an effective consolidative strategy, while its optimal positioning alongside emerging therapies requires further study.

Combined oral contraceptives are widely used and generally considered safe. However, they have been associated with arterial thrombosis, including myocardial infarction, particularly in women with cardiovascular risk factors. This case adds to the limited literature highlighting the potential for combined oral contraceptive-induced myocardial infarction in individuals without traditional cardiovascular risk factors. A 28-year-old non-smoking Iranian woman with no significant medical history presented with 11h of typical anginal chest pain radiating to the left arm and interscapular area. Electrocardiography revealed ST-segment elevations in leads V2-V5, and cardiac biomarkers confirmed myocardial infarction. She had been taking a second-generation combined oral contraceptive containing 150µg levonorgestrel and 30µg ethinyl estradiol for 13years. Emergent coronary angiography demonstrated a thrombotic occlusion in the mid-left anterior descending artery without evidence of underlying atherosclerosis. Successful reperfusion was achieved via balloon angioplasty without stenting. The patient remained stable, was discharged on optimal medical therapy, and advised to discontinue combined oral contraceptives. At 3-month follow-up, cardiac Computed Tomography Angiography revealed a patent left anterior descending artery with no residual stenosis, and echocardiography showed improved systolic function. This case underscores the potential for thrombotic myocardial infarction in young women using combined oral contraceptives, even in the absence of conventional risk factors. It highlights the importance of considering hormonal contraceptive history in the diagnostic workup of acute coronary syndromes in young females. In addition, it demonstrates that Balloon angioplasty without stent placement may be effective in selected cases of non-atherosclerotic thrombotic occlusion.

Heart failure (HF) continues to be a major global health burden, with persistent morbidity and mortality despite guideline-directed and device-based therapies. Evidence suggests the gut-heart axis is a critical and underrecognized contributor to HF progression. Alterations in cardiac output and systemic venous congestion in HF lead to intestinal hypoperfusion, mucosal edema, and loss of barrier integrity, increasing intestinal permeability, gut dysbiosis, and translocation of microbial products. This systemic translocation is associated with chronic low-grade inflammation that activates innate immune pathways that correlate with endothelial dysfunction, oxidative stress, fibroblast activation, and adverse cardiac remodeling. Gut-derived metabolites derived by microbial metabolism modulate cardiovascular health by altering the metabolic profiles. Dysbiosis results in loss of protective short-chain fatty acid (SCFA)-producing bacteria and enriches pro-inflammatory taxa such as trimethylamine N-oxide (TMAO)-producing bacteria. Elevated TMAO is associated with increased mortality and hospitalization in HF, whereas SCFAs enhance barrier integrity and immune tolerance. Secondary bile acids and uremic toxins such as indoxyl sulfate and p-cresyl sulfate further link dysbiosis to fibrosis and vascular stiffness. Circulating markers such as TMAO, lipopolysaccharide-binding protein (LBP), and soluble CD14 carry prognostic value beyond traditional cardiac biomarkers. This review highlights current experimental, translational, and clinical evidence describing gut dysbiosis and its molecular links to HF progression. Targeting the gut-heart axis represents a novel therapeutic approach in HF. Dietary modulation, probiotics/prebiotics, fecal microbiota transplantation, and inhibitors of microbial metabolic pathways show promise. Future research should emphasize microbiota-based interventions in HF management.

Cardiotoxicity from anti-leukemic therapies remains a major concern in pediatric hemato-oncology-often subclinical in the short term but potentially life-threatening in the long term. In children, who are exposed to cardiotoxic treatments at an early age and have long life expectancies, a proactive strategy for prevention, early detection, and management is essential. Anthracyclines remain a cornerstone of pediatric acute leukemia treatment but are associated with a risk of heart failure in approximately 10% of cases, particularly at cumulative doses exceeding 300mg/m2 of doxorubicin-equivalent. Dexrazoxane, once controversial, is now supported by robust data demonstrating both safety and cardioprotective efficacy. Its use is recommended alongside anthracyclines in patients receiving a cumulative dose≥300mg/m2 of doxorubicin-equivalent. Other agents -including tyrosine kinase inhibitors, immunotherapies, and CAR-T cells- also carry cardiotoxic potential, warranting tailored monitoring strategies. These multidisciplinary SFCE-endorsed recommendations emphasize the need for early and repeated assessment of cardiovascular risk factors throughout treatment. A dedicated heart team, involving pediatric cardiologists and pediatric hematologists, should coordinate active surveillance, including management of modifiable cardiovascular risk factors and systematic imaging with global longitudinal strain, which is more sensitive than ejection fraction in detecting subclinical dysfunction. Prospective pediatric studies are needed to define age-appropriate imaging thresholds, validate the role of cardiac biomarkers, and assess liposomal anthracycline formulations. If confirmed to be both safe and effective, such agents should be integrated into future treatment protocols to enhance long-term cardioprotection without compromising anti-leukemic efficacy.

Fabry disease (FD) is a rare lysosomal storage disorder with cardiac involvement. The efficacy of cardiac assessments in predicting disease progression is uncertain and few long-term studies have evaluated a clinically comprehensive approach in tracking cardiac outcomes. We developed a multi-modal framework integrating sex, genetics, clinical assessments, electrocardiography (ECG), imaging, and biomarkers to characterize the progression of cardiac involvement in FD and assess the predictive value of each modality for adverse cardiovascular outcomes. Our cohort encompassed 525 "visit years" across 98 participants (60 females; 60 with classic mutations; mean age at presentation: 42.5 ± 17). We defined four cardiac phenotypic clusters (CPC): abnormal ECG, elevated cardiac biomarkers, left ventricular hypertrophy (LVH) (by echocardiography or cardiac magnetic resonance [CMR]), and late gadolinium enhancement (LGE) (by CMR). The primary outcome was a composite of cardiac hospitalization, device implantation, or cardiovascular/cerebrovascular death. A CPC progression map was plotted, outlining the course of events in FD cardiomyopathy, where changes in ECG and the occurrence of hypertrophy precede increase in cardiac biomarkers and the formation of LGE. Mutation type (classic vs. late-onset) and sex (female vs. male) showed a significant link with a composite outcome of cardiac-related hospitalizations, device implantations (defibrillator/pacemaker), and cardiovascular or cerebrovascular mortality [Hazard ratio, HR (95% confidence interval, CI, p-value): 12.8 (3.5,46.7), p = 0.0001 and 0.09 (0.03,0.33), p = 0.0002, respectively]. The presence of LGE CPC was associated with an increased likelihood of encountering the composite outcome. We propose a readily-applied "4 domain CPC" model, that can be routinely used in clinical practice, as a prospective "guide-map" for FD cardiomyopathy progression. Its utility is demonstrated in showing the expected role of sex, mutation and CMR findings in the cardiac trajectory of FD.