Search Results (207)

Introduction: Kawasaki disease (KD) is an acute systemic vasculitis and the leading cause of acquired pediatric heart disease in high-income countries. Coronary artery aneurysms (CAA) represent the most severe complication and drive long-term cardiovascular risk. Despite improved outcomes with early intravenous immunoglobulin therapy, follow-up strategies remain heterogeneous, particularly for patients showing CAA regression. Dynamic risk stratification based on coronary Z-scores has been proposed, but long-term real-world data are still needed to optimize surveillance. Methods: We conducted a single-center, retrospective study including pediatric patients (age 1 month–18 years) with KD complicated by CAA, followed at Bambino Gesù Children’s Hospital (Rome) between 1999 and 2024. Coronary involvement was assessed using Boston Z-scores of the right coronary artery, left main coronary artery, and left anterior descending artery. CAA severity over time was analyzed using a composite MAX SCORE (highest Z-score among coronary branches) along with the 1-YEAR MAX SCORE (highest MAX SCORE reached within the 1 year of disease). The distribution and timing of cardiac computed tomography angiography (CCTA) and exercise stress testing (EST) during follow-up were analyzed in relation to coronary severity. Results: Among 502 KD patients, 122 (24.3%) developed CAA; 113 were included in the analysis. Mean age at diagnosis was 24.6 months (M/F 3.5:1). Multivessel involvement was observed in 72%, most frequently affecting the left anterior descending artery. Long-term follow-up ≥10 years was available for 31.9% of patients. Most changes in coronary severity occurred within the first year after disease onset, with complete CAA regression in 76.1% of patients. Conversely, 53% of patients affected by giant aneurysms at 12 months showed persistent severe disease at last follow-up. EST (164 tests in 40 patients) was almost universally negative for inducible ischemia (163/164), whereas CCTA (47 exams in 35 patients) was preferentially performed early and in higher-risk patients. Test prescription correlated more closely with 1-YEAR MAX SCORE than with contemporaneous severity. Echocardiography showed systematic differences compared with CCTA for right coronary and left anterior descending artery Z-scores. Discussion: In our experience, early coronary status was closely associated with the intensity of long-term surveillance strategies in KD. The 1-YEAR MAX SCORE was associated with subsequent patterns of coronary evolution, and the continuous 1-year Maximum Z-score showed good discriminatory ability for persistent CAA on ROC analysis, pending external validation. While the low rate of positive findings on EST raises questions about its diagnostic yield in real-world practice, CCTA provided detailed anatomical characterization. Overall, these findings suggest that early coronary severity may help inform individualized, severity-driven follow-up strategies, warranting confirmation in prospective multicenter studies. Full article

Background: Renal artery resistive index (RI) may reflect renal–vascular adaptation in preterm neonates, but its ability to distinguish early hypertension from acute kidney injury (AKI) remains uncertain. Methods: This prospective cohort study enrolled preterm neonates born at 28–34 weeks’ gestation at Dr. Hasan Sadikin Hospital, Indonesia. Renal Doppler ultrasonography was performed at 72 h of life to measure the RI of the right and left renal arteries. Blood pressure was assessed during the first postnatal week using repeated non-invasive oscillometric measurements. AKI was defined according to neonatal Kidney Disease: Improving Global Outcomes criteria. Associations between RI, early-onset hypertension, and AKI were evaluated using bivariate analyses, receiver operating characteristic curves, and exploratory adjusted logistic regression. Results: Of 113 eligible infants, 77 completed follow-up evaluation. Higher RI values were associated with early-onset hypertension in univariable analyses for both the right (p = 0.010) and left (p = 0.038) RI. RI thresholds > 0.94 for the right renal artery and >0.87 for the left renal artery were associated with increased risk of hypertension. RI values did not differ significantly between infants with and without AKI. Exploratory adjusted analyses showed attenuation of side-specific associations, whereas the higher bilateral RI value suggested a modest hypertension-related signal. Conclusions: In this cohort of clinically stable surviving preterm neonates, renal artery RI showed a clearer association with early-onset hypertension than with AKI classified using the study’s operational KDIGO approach. RI may provide adjunctive physiological information regarding vascular impedance and early cardiovascular–renal adaptation, but it should not be interpreted as a specific or stand-alone biomarker of hypertension or kidney injury. These findings are hypothesis-generating and require validation in larger multicenter cohorts using serial renal and hemodynamic assessments. Full article

Background: Lipoproteins are molecules composed of phospholipids and apolipoproteins that transport triacylglycerol and cholesterol in blood and are implicated in the development of many diseases. Methods: In this study, we fill a knowledge gap by precisely characterizing the apolipoprotein profile (with Bio-Plex Human Apolipoprotein Assay) in three metabolically separate groups of individuals (lean individuals and obese individuals without and with metabolic syndrome) and at four distinct time points (0, 3, 6, and 12 months post bariatric surgery). Results: Obese patients had a higher baseline ApoB/ApoA1 ratio, which returned to the reference level over the follow-up period. The above is of clinical importance, as the ratio is a predictor of adverse cardiovascular events common in obese subjects. Interestingly, plasma concentrations of most of the investigated apolipoproteins appeared to be relatively stable at the onset of the experiment, with changes observed later in time. We detected significant drops in the levels of ApoC3, ApoD, and ApoH that occurred as early as three months post intervention. On the other hand, the levels of ApoA2, ApoE, and ApoJ increased with time. Of the above, ApoE is known to be involved in the removal of TAGs and cholesterol from the blood. Conversely, ApoJ appears to be one of the determinants of the tissues’ responsiveness to insulin. Thus, it may be an indicator of the reduced insulin resistance observed a few months after the surgery. Conclusions: Overall, the investigated proteins have a documented role in the development and progression of vascular pathologies. Hence, our results may be interpreted as a sign of improved cardiovascular fitness of our patients. Full article

Per- and polyfluoroalkyl substances (PFAS) are persistent environmental contaminants increasingly associated with cardiovascular disease. Identifying early manifestations of vascular aging before the onset of overt disease is essential for improving cardiovascular risk stratification and prevention. Emerging evidence suggests that PFAS exposure contributes to early vascular and atherosclerotic alterations detectable by imaging techniques, including increased carotid intima–media thickness (CIMT), arterial stiffness, and endothelial dysfunction. In contrast, evidence for associations with coronary artery calcium progression and coronary stenosis remains scarce. Mechanistically, PFAS exposure promotes endothelial dysfunction, oxidative stress, chronic inflammation, lipid dysregulation, and genetic and epigenetic modifications, all of which contribute to premature vascular aging and metabolic disturbances. The integration of imaging and molecular biomarkers may provide complementary insights into the structural, functional, and biological processes underlying PFAS-related vascular damage; however, to date, this field remains largely unexplored. This narrative review summarizes current evidence on imaging and molecular biomarkers of PFAS-induced vascular aging and discusses their potential role in cardiovascular risk assessment. It also highlights key knowledge gaps and the need for robust epidemiological and multi-omics studies to validate these biomarkers, clarify causal mechanisms, and support their application in cardiovascular and environmental health surveillance. Full article

Rotavirus infection is a major cause of acute gastroenteritis in children, which is characterized by fever, emesis, and diarrhea. In some children, rotaviral infection can spread beyond the gastrointestinal tract and affect the nervous system, kidneys, liver, or pancreas. There are relatively few longitudinal studies of such long-term sequalae. One area of interest has been damage to pancreatic beta islet cells, the lack of which causes type 1 diabetes mellitus. This chronic disease can be life threatening, especially in young children, and is associated with lifelong elevated risks of cardiovascular disease, neuropathy, nephropathy, and retinopathy. This narrative review summarizes the scientific evidence relevant to rotavirus infection and early-onset type 1 diabetes. The results of epidemiologic, animal, and laboratory research indicate that rotavirus infection increases the risk of type 1 diabetes in young children (<5 years of age). Rotavirus vaccination is associated with lower incidence rates; the data suggest a somewhat stronger effect with the pentavalent vaccine than the monovalent vaccine. Continued surveillance of both rotavirus infection and type 1 diabetes are necessary, considering the increases in vaccine hesitancy. The benefits of rotavirus vaccination should be discussed with parents and individuals planning to have children. Full article

The global burden of diabetes mellitus and its chronic complications—including premature atherosclerotic cardiovascular disease and microvascular impairments such as nephropathy, retinopathy, and neuropathy—highlights the need for improved strategies for the early identification of individuals at risk of carbohydrate metabolism disorders. Growing evidence suggests that alterations in the microcirculatory bed occur concomitantly with, or may even precede, the development of cardiovascular disease. The eye, owing to its transparent anatomical structures, provides a unique opportunity for the in vivo assessment of microvascular changes and offers valuable insights into other vascular territories, serving as a potential “window” into cardiometabolic disorders. Recent advances in microcirculation imaging have enabled detailed, non-invasive evaluation of the retinal microvasculature. Techniques such as scanning laser Doppler flowmetry (SLDF), adaptive optics (AO), optical coherence tomography angiography (OCTA), and laser speckle flowgraphy (LSFG) allow for quantitative assessment of the retinal microvascular bed, demonstrating partial correlation with invasive measures of vascular function and sensitivity to therapeutic interventions. The integration of these imaging modalities into clinical and research settings may facilitate the early detection of microvascular dysfunction, improve risk stratification, and support the monitoring of disease progression and treatment efficacy in patients with carbohydrate metabolism disorders. Therefore, this review aims to summarize the current evidence on retinal microvascular alterations in carbohydrate metabolism disorders assessed using advanced imaging techniques, focusing primarily on early, subclinical retinal changes that precede the onset of diabetic retinopathy. Full article

Background: Acute exacerbation of obstructive airway disease (AEOAD) is a major cause of hospitalization, morbidity, and premature mortality in India. Hospitalized patients for the same are predominantly treated with short-acting bronchodilators, which require frequent administration and are associated with systemic adverse effects. Despite the availability of nebulized long-acting muscarinic antagonists (LAMAs) with quick onset of action, such as glycopyrronium, their role in acute care remains unclear in India. Methods: A pan-India expert opinion-building initiative was conducted among 220 pulmonologists across Tier I–II cities through 13 structured advisory meetings between April 2025 and July 2025. The final expert perspectives were then categorized into recurrent insights, raised in 75% or more meetings, and variable insights, raised in <75% of all meetings. Results: Experts reported that AEOAD management commonly involved initial stabilization with SABA/SAMA followed by transition to triple therapy with nebulized glycopyrronium, formoterol, and budesonide. Nebulized glycopyrronium was perceived to provide rapid and sustained bronchodilation with fewer cardiovascular side effects compared to short-acting agents. Benefits were reported in patients with frequent exacerbations, high sputum burden, and bronchiectasis. Operational advantages included reduced dosing frequency and nursing workload. Experts also noted potential improvements in hospital stay and readmissions; however, these observations were based on clinical experience rather than controlled data. Conclusions: Indian pulmonologists agreed that early initiation of nebulized glycopyrronium (with formoterol and budesonide) in hospitalized AEOAD may improve symptom control, lower exacerbation burden, reduce reliance on short-acting bronchodilators and corticosteroids, and shorten hospital stays. Full article

Myxomatous mitral valve disease (MMVD) is the most common acquired cardiac disease in small-breed dogs and shows particularly high prevalence and early onset in Cavalier King Charles Spaniels (CKCS). Although MMVD is considered a complex, polygenic disease, the clinical relevance of individual genetic variants remains incompletely understood. The angiotensin-converting enzyme (ACE) gene variant rs850683722 has previously been associated with altered ACE activity and differences in renin–angiotensin–aldosterone system-related responses in dogs with MMVD. The aim of this study was to determine the prevalence of rs850683722 in a Polish population of CKCS dogs and to assess whether this variant is associated with the clinical course of MMVD. A total of 105 CKCS dogs were included in the study. All dogs underwent standardized cardiovascular evaluation, including echocardiography, electrocardiography, and systolic blood pressure measurement. MMVD diagnosis and staging were performed according to current ACVIM consensus criteria. Genotyping of the rs850683722 variant was performed using Sanger sequencing for 95 dogs, while next-generation sequencing data was obtained for 10 dogs. Genotype distribution, allele frequencies, conformity with the Hardy–Weinberg equilibrium (HWE), sex-related differences, and associations between genotype and age at progression to selected MMVD stages or the primary clinical endpoint were assessed statistically. The most frequent genotype was AA, detected in fifty-nine dogs, followed by GG in thirty-seven dogs and AG in nine dogs. When dogs carrying at least one A allele were considered variant-positive, the overall prevalence of the variant-positive genotype was 64.8%. The calculated allele frequencies were 0.605 for the A allele and 0.395 for the G allele. The observed genotype distribution deviated markedly from the Hardy–Weinberg equilibrium, mainly because of a pronounced deficit of heterozygous dogs. No significant association was detected between genotype and sex. Genotype was also not significantly associated with age at progression to stage B2 or stage C. A statistically significant difference in age of death was demonstrated by genotype, but this difference was not reflected in the survival analysis. The rs850683722 variant was highly prevalent in the studied Polish CKCS population, with a frequency comparable to previously reported data for this breed. Despite its documented biological association with ACE activity and RAAS-related responses, the variant was not significantly associated with the clinical progression of MMVD in this cohort. These findings suggest that rs850683722 alone seems unlikely to be a reliable marker for predicting the severity or rate of MMVD progression in Polish CKCS dogs. Further studies including larger cohorts, longer follow-up, pedigree information, and the direct assessment of RAAS activity may help clarify whether this variant has stage-dependent or treatment-related clinical relevance. Full article

Background and Clinical Significance: Childhood-onset Sjögren’s disease (cSjD) is a rare autoimmune disorder that remains challenging to diagnose because of its heterogeneous clinical presentation and the frequent absence of classic sicca symptoms at disease onset. Recurrent parotitis and systemic manifestations often predominate in pediatric patients, contributing to diagnostic delay and potential irreversible glandular damage. Early recognition is essential to prevent complications and improve long-term outcomes. Case Presentation: We report the case of a 17-year-old female diagnosed with primary Sjögren’s disease following a prolonged history of recurrent parotid involvement and progressive glandular dysfunction. Comprehensive evaluation revealed positive anti-SSA antibodies, hypergammaglobulinemia, characteristic salivary gland ultrasonography abnormalities, and a positive minor salivary gland biopsy, resulting in fulfillment of all domains of the 2016 ACR/EULAR classification criteria. The patient also exhibited unusual vascular findings, including carotid atheromatous calcifications in the absence of traditional cardiovascular risk factors. Conclusion: This case highlights the diagnostic complexity of cSjD and underscores the value of a multimodal diagnostic approach integrating clinical assessment, serology, imaging, and histopathology. The presence of early vascular abnormalities broadens the spectrum of potential extraglandular manifestations and emphasizes the need for comprehensive evaluation and long-term monitoring in affected patients. Full article

Background and Objectives: To investigate prognostic risk factors and determine the incidence, clinical characteristics, and predictors of heart failure (HF) development in pediatric patients with end-stage kidney disease (ESKD) secondary to steroid-resistant nephrotic syndrome (SRNS). Materials and Methods: We conducted a retrospective cohort study of pediatric patients diagnosed with ESKD secondary to nephrotic syndrome (NS) between 2014 and 2020. Patients were stratified based on clinical outcomes and the occurrence of HF during follow-up. Comparative analyses of clinical characteristics, laboratory parameters, and cardiac assessments were performed across groups. Multivariate logistic regression was used to identify independent risk factors for HF development within the first year and for adverse prognosis at five years. Results: The cohort comprised 172 children with ESKD secondary to NS. Multivariate logistic regression identified HF as an independent risk factor for adverse long-term outcomes in pediatric patients with ESKD. During follow-up, HF developed in 27 patients (15.7%) within the first year after ESKD diagnosis, and in 45 patients (26.2%) by the end of five years. Early HF onset (within the first year) was associated with a significantly reduced five-year survival rate. Independent risk factors for HF development included elevated cardiac troponin I levels (OR = 6.786, 95% CI: 2.326–19.799), a history of cardiac arrhythmias (OR = 2.951, 95% CI: 1.260–6.912), and the presence of left heart enlargement (OR = 23.669, 95% CI: 2.876–194.827), and valvular regurgitation at the initial post-ESKD diagnosis evaluation. Conclusions: HF is associated with markedly reduced survival. Crucially, our findings demonstrate that pre-existing cardiovascular structural abnormalities—specifically left heart enlargement—and elevated cTnI are robust, early predictors of HF. These findings necessitate a paradigm shift in pediatric ESKD management, we advocate for the implementation of systematic baseline echocardiographic and biomarker screening at the immediate onset of ESKD. Identifying these subclinical, yet modifiable, structural changes provide a critical therapeutic window for targeted anti-remodeling interventions to significantly improve long-term prognosis. Full article

Aging is a significant risk factor for cardiovascular diseases. The prevalence of heart failure increases with age, making it a leading cause of morbidity and mortality. We investigated age-associated changes in expression of Nuclear Factor (Erythroid-derived 2)-Like 2 (NFE2L2 or NRF2) in the myocardium of humans, rhesus monkeys, Fischer rats, and C57BL/6 mice. NRF2 is a transcription factor that orchestrates the expression of genes involved in antioxidant and detoxification responses. Analyses of RNA-seq data from the Genotype-Tissue Expression (GTEx) project, which contains left ventricular samples from 294 male donors, revealed a trend of age-associated declines in NRF2 transcripts and several of its downstream genes (SOD1, SOD2, CAT, GCLM, and AKR1B). Age-dependent decreases in NRF2 protein expression were observed in the myocardium of Rhesus monkeys and Fischer rats. To determine whether NRF2 loss contributes to myocardial aging, we evaluated cardiac function of NRF2 knockout mice (KO) at 19 and 24 months of age. At 19 months, the NRF2 KO mice exhibited diastolic dysfunction, characterized by an increased end-diastolic volume (EDV) and end-systolic volume (ESV), accompanied by a reduced ejection fraction (EF) and fractional shortening (FS), indicative of early onset of heart failure. The NRF2 KO mice displayed premature aging phenotypes and had reduced lifespans. Our findings support the trend of NRF2 signaling decline with age, and that loss of NRF2 accelerates the maladaptive cardiac remodeling and functional deterioration associated with aging. Full article

Background and Aims: Atherosclerotic cardiovascular disease (ASCVD) remains a leading cause of mortality worldwide, with lipid abnormalities playing a central role in disease development. While the causal role of low-density lipoprotein cholesterol (LDL-C) in ASCVD is well-established, the long-term population impact of combined lipid profiles, particularly the HDL-C/LDL-C ratio, remains less clearly quantified. This study aimed to estimate the lifetime burden of cardiovascular outcomes associated with different lipid risk profiles using a patient-level simulation framework. Methods: The authors analyzed projected lifetime ASCVD events across four HDL-C/LDL-C risk strata, ranging from low (≥0.45) to very high (<0.25), using the National Health Model Database of Projected and Estimated Outcomes (NHM-DPEO)—a digital twin of national healthcare systems built from multiple data sources, including national health and demographic statistics and estimates from the relevant literature. The framework is structured as a patient-level simulation model that projects individual health trajectories over a lifetime horizon. Model outputs were assessed for plausibility by comparison with published epidemiological estimates. Results: The NHM simulation revealed a strong, graded relationship between lipid profiles and cardiovascular survival. Life expectancy declined from 80.2 years in the lowest risk group (HDL-C/LDL-C ≥ 0.45) to 63.0 years in the very-high-risk group (HDL-C/LDL-C < 0.25), a reduction of 17.2 years, with 13.7 fewer QALYs. Similarly, participants with LDL-C > 5.0 mmol/L had a life expectancy 13.4 years shorter than those with LDL-C < 3.1 mmol/L. The burden of ASCVD increased exponentially with worsening lipid ratios: MI events rose from 5000 to 73,090 per 100,000 births, with onset in the highest risk group occurring as early as age 20. Ischaemic heart disease followed a similar pattern, showing up to 92% of events attributable to elevated lipid risk. While ischaemic stroke risk displayed a more complex pattern due to earlier MI mortality in high-risk groups, overall cardiovascular mortality and lifetime event burden were dominated by LDL-driven disease. These findings demonstrate that sustained LDL-C reduction and balanced HDL-C/LDL-C ratios confer substantial survival benefits across both sexes and all age groups. Conclusions: This study shows that lipid balance has a decisive influence on cardiovascular survival. Sustained LDL-C reduction and favourable HDL-C/LDL-C ratios markedly extend life expectancy and delay the onset of MI and IHD. The magnitude of this survival benefit highlights the need for early and continuous lipid control as a cornerstone of ASCVD prevention. The NHM quantifies these lifetime effects, offering valuable insights for targeted strategies that improve both longevity and quality of life. Full article

Mulibrey nanism is a rare autosomal recessive multisystem disorder caused by biallelic loss of function variants in TRIM37 encoding a peroxisomal E3 ubiquitin ligase. Initially described in Finland, where it remains most prevalent due to a founder mutation, the condition is now recognized worldwide and is characterized by severe prenatal-onset growth failure, distinctive craniofacial features, radiological abnormalities, ocular findings, and hepatopathy. Although its clinical spectrum extends far beyond these core manifestations, the major determinant of morbidity and mortality is progressive cardiovascular disease, including constrictive pericarditis and restrictive cardiomyopathy. Additional features include metabolic dysfunction such as insulin resistance and type 2 diabetes, gonadal insufficiency, skeletal abnormalities including fibrous dysplasia, and an increased risk of benign and malignant tumours. The clinical course evolves across the lifespan from early growth and developmental abnormalities to progressive multisystem disease in adolescence and adulthood. Recent advances have expanded understanding of TRIM37 function, linking it to mTORC1 TFEB signalling autophagy, centrosome integrity, extracellular matrix regulation, and immune cell function, providing mechanistic insights into tumour predisposition, skeletal pathology, and immune dysregulation. Management remains supportive and requires multidisciplinary care with emphasis on early recognition and treatment of cardiac disease, metabolic complications, and malignancy risk. Prognosis is variable but improves with early diagnosis and appropriate surveillance. This review summarises the clinical spectrum molecular mechanisms and current management of Mulibrey nanism and highlights priorities for future research. Full article

Cardiovascular diseases are the primary causes of mortality worldwide, often characterized by subtle onset and acute progression. Traditional ECG electrodes may cause skin irritation, limiting routine monitoring and early risk assessment. Relying on the advantages of non-contact monitoring, millimeter-wave radar-based cardiac monitoring combined with deep learning has become a popular research direction recently. To overcome the poor generalization of methods trained from single-source datasets, this study designed seven experimental scenarios covering wakefulness and sleep. A novel deep learning network consisting of encoder and decoder structures named PMG-SATNet was proposed. The encoder comprises a parallel multi-scale feature extraction module and a global temporal relationship modeling module to capture fine-grained local patterns and long-range dependencies. The decoder employs a temporal convolutional network augmented with a spectral attention mechanism to emphasize clinically relevant ECG frequency bands and suppress respiration and body motion interference. After being validated on the self-built dataset, PMG-SATNet outperformed baseline models in terms of Pearson correlation coefficient and root mean square error, with an improvement of 3.3% and 3.8%, and 16.4% and 23.8%, respectively. The validation results imply that PMG-SATNet is capable of recovering ECG signals from millimeter-wave radar-derived chest vibrations with high fidelity and can potentially be implemented in real-life cardiac health monitoring. Full article

Nitric oxide (NO) functions as a master integrative regulator of cardiovascular–kidney–metabolic (CKM) homeostasis, yet it displays a profound Janus face, defined by concentration- and context-dependent roles in both health and disease. This narrative review examines NO signaling from a life-course perspective, beginning with fetal programming, during which the NO–asymmetric dimethylarginine (ADMA) axis orchestrates placental development and nephron endowment. Perturbations during this critical window—such as maternal ADMA elevation—can imprint a maladaptive trajectory toward adult-onset hypertension and chronic kidney disease. In adulthood, this initially silent dysregulation of NO signaling is amplified by Western dietary patterns and environmental pollutants, culminating in the clinical manifestation of the CKM triad. This pathological transition is driven by eNOS uncoupling and ADMA accumulation, which shift redox balance toward peroxynitrite formation and precipitate mitochondrial bioenergetic failure. Moreover, while constitutive NO production is essential for vascular homeostasis, pathological induction of inducible NOS generates excessive NO fluxes that promote insulin resistance and tissue injury. With advancing age, a progressive loss of NO resilience further exacerbates multi-organ vulnerability. To mitigate the cumulative burden of CKM disease, this review highlights developmental reprogramming strategies—such as perinatal L-citrulline supplementation and ADMA-lowering interventions—as interventions to restore physiological NO signaling. Integrating such early-life strategies with contemporary pharmacological therapies offers a coherent framework for maintaining NO bioavailability and extending health span across the life course. Full article