Search Results (629)

Background/Objectives: Heart failure (HF) is associated with substantial morbidity, impaired quality of life (QOL), and reduced functional capacity. In selected patients with symptomatic HF despite Optimal Medical Therapy (OMT), Cardiac Contractility Modulation (CCM) may be a therapeutic option. Identifying patients most likely to benefit from CCM remains an unmet need. The Predict-CCM study aims to evaluate long-term clinical and objective outcomes after CCM therapy and to assess the predictive value of pre-implant low-dose dobutamine stress echocardiography (LDDSE). Methods and Results: Predict-CCM is an independent, non-profit, multicenter, observational cohort study conducted in Italy, with both retrospective and prospective enrollment. The primary endpoint is the proportion of subjects with a clinical response to CCM at 12 months, defined as a ≥1-class reduction in NYHA class. Secondary clinical endpoints include reductions in HF-related hospitalizations, changes in QOL assessed by the Minnesota Living with Heart Failure Questionnaire (MLHFQ), and changes in NT-proBNP levels from baseline to follow-up. Outcomes will be evaluated in the overall cohort and in two subcohorts stratified by pre-implant LDDSE response: (1) reduction in left ventricular end systolic volume (LVESV) ≥ 15% (DeltaLVESV ≥ 15%); and (2) reduction in LVESV < 15% (DeltaLVESV < 15%). Assuming a 70% clinical response rate at 12 months, the estimated sample size is 120 patients. The study was approved by the Ethics Committee in March 2025. Enrollment will continue for 2 years, with a 12-month follow-up period after implant for each subject. Conclusions: This study may provide new criteria for patient selection and outcome assessment in CCM therapy. Left ventricular contractile reserve assessed by stress echocardiography may be a promising predictor of response. Full article

Background/Objectives: Cognitive impairment is highly prevalent in atrial fibrillation (AF) and frequently occurs in the absence of overt stroke, implicating non-embolic mechanisms. We hypothesized that atrial remodeling and impaired cerebral hemodynamics are associated with mild cognitive impairment (MCI) in permanent AF. Methods: In this cross-sectional study, 252 stroke-free patients with permanent AF receiving direct oral anticoagulants (DOACs) underwent transthoracic echocardiography and transcranial Doppler (TCD) assessment of middle cerebral artery flow. Peak systolic velocity (PSV), end-diastolic velocity (EDV), and resistive index (RI) were analyzed. Multivariable logistic regression identified factors independently associated with MCI, and receiver operating characteristic (ROC) curves evaluated discriminative performance. Results: MCI was present in 40% of patients (101/252). AF-MCI patients were older and showed greater left atrial remodeling, reflected by increased left atrial diameter and left atrial volume index (LAVI) (both p ≤ 0.001), without differences in left ventricular systolic function. TCD demonstrated reduced EDV and increased RI in the MCI group (all p ≤ 0.01), whereas PSV showed minimal differences. In multivariable analysis, age, LAVI, and average RI were independently associated with MCI. Age showed excellent discrimination (AUC 0.858), whereas maximum RI demonstrated moderate discrimination (AUC 0.645; p < 0.001 for comparison). Conclusions: In stroke-censored permanent atrial fibrillation, cognitive impairment was associated with atrial remodeling and impaired diastolic cerebral perfusion, consistent with a potential contribution of chronic hypoperfusion and increased microvascular resistance. Combined echocardiographic and cerebral hemodynamic assessment may help characterize hemodynamic patterns associated with cognitive impairment in AF. Full article

Introduction: Hypertrophic cardiomyopathy (HCM) is a common myocardial disease worldwide and is associated with heart failure symptoms and sudden cardiac death. In a subset of patients, it may produce dynamic left ventricular outflow tract obstruction (LVOTO) and systolic anterior motion (SAM)-related mitral valve dysfunction through drag forces and altered mitral–septal geometry. In contrast, subaortic stenosis caused by a subaortic membrane is an uncommon congenital lesion that may lead to fixed subvalvular LVOTO in adulthood. The coexistence of these entities is rare and can substantially complicate diagnosis and management. Case presentation: A 51-year-old woman with HCM, paroxysmal atrial fibrillation, and heart failure presented with acute decompensation and cardiogenic shock. After initial hemodynamic stabilization and cardioversion for atrial fibrillation with rapid ventricular response, multimodality imaging with transthoracic and transesophageal echocardiography, coronary computed tomography angiography, and cardiac magnetic resonance demonstrated dual LVOTO, with a dynamic component related to HCM/SAM physiology and a fixed component caused by an elongated subaortic membrane, accompanied by severe SAM-related mitral regurgitation. Echocardiography showed a resting peak LVOT gradient of 49 mmHg, increasing to 85 mmHg with the Valsalva maneuver. After exclusion of obstructive coronary artery disease and evaluation for selected phenocopies, the patient underwent septal myectomy, subaortic membrane resection, and adjunctive mitral valve plication. Early postoperative echocardiography showed reduction in the maximum provoked LVOT gradient to 38 mmHg and improvement of mitral regurgitation from severe to mild. At 3-month follow-up, she remained in sinus rhythm, improved to New York Heart Association functional class II, and had no documented readmissions for heart failure. Conclusions: Combined fixed and dynamic LVOTO due to concomitant subaortic membrane and HCM is exceedingly rare. Accurate diagnosis requires a high index of suspicion and a multimodality imaging strategy to define the obstructive mechanisms and support mechanism-based surgical management and avoid incomplete treatment when a coexisting fixed lesion is present. Full article

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

Background: Renal dysfunction is common in patients hospitalized with acute decompensated heart failure (ADHF) and represents a key component of cardiorenal syndrome. However, the relationships between renal impairment, cardiorenal biomarkers, and echocardiographic markers of myocardial function remain incompletely characterized in ADHF populations. Methods: We conducted a cross-sectional analysis of 144 consecutive patients hospitalized with ADHF. Renal dysfunction was defined as an estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m². Clinical, laboratory, and echocardiographic parameters were compared according to renal function. Correlation analyses, multivariable logistic regression, and receiver operating characteristic (ROC) curve analyses were performed to evaluate associations between renal dysfunction, cardiorenal biomarkers, and myocardial functional indices. Results: Patients with renal dysfunction were older (p = 0.002) and more frequently had diabetes mellitus (p = 0.006). Echocardiographic evaluation demonstrated significantly lower systolic mitral annular velocity (S′) (p < 0.001) and higher E/e′ ratios (p < 0.001) in patients with renal dysfunction, whereas left ventricular ejection fraction (p = 0.133) and global longitudinal strain (GLS) (p = 0.121) were similar between groups. Log-transformed NT-proBNP and albuminuria were significantly correlated with S′, GLS, and E/e′ (all p < 0.001). In multivariable analysis adjusted for clinically relevant confounders, chronic kidney disease (OR 8.16, 95% CI 2.13–31.34; p = 0.002) and the E/e′ ratio (OR 2.01, 95% CI 1.52–2.66; p < 0.001) remained independently associated with renal dysfunction. ROC analysis showed that E/e′ had the strongest ability to distinguish between patients with and without renal dysfunction (AUC 0.887, 95% CI 0.834–0.941; p < 0.001). Conclusions: Renal dysfunction in ADHF is associated with echocardiographic markers reflecting impaired longitudinal myocardial function and elevated filling pressure, with E/e′ emerging as the strongest echocardiographic correlate. The integration of echocardiographic parameters with cardiorenal biomarkers may improve the characterization of the cardiorenal profile in patients hospitalized with ADHF. Full article

Background: Perioperative cardiovascular risk assessment remains challenging in non-cardiac surgery, particularly in older patients and those with multiple comorbidities. Traditional models rely largely on clinical history and may not fully reflect current cardiovascular functional status. This study aimed to derive and assess the apparent performance of a new composite score, PERFORM-CV, integrating clinical, laboratory, and echocardiographic data. Methods: We conducted a prospective two-center cohort study including 503 non-cardiac surgical patients with cardiovascular comorbidity. The Revised Cardiac Risk Index (Lee/RCRI) and the AUB-HAS2 index were calculated according to their original published definitions as raw point totals ranging from 0 to 6; without additional normalization. The PERFORM-CV score was derived from univariable and multivariable analyses, with continuous predictors dichotomized using ROC-derived thresholds. Results: Emergency admission, chronic heart failure, and elevated serum creatinine remained independently associated with in-hospital mortality. Lower left ventricular ejection fraction, lower mitral annular plane systolic excursion (MAPSE), lower hemoglobin, and atrial fibrillation also contributed to the final composite score. ROC analysis showed good discrimination for PERFORM-CV (AUC 0.852; 95% CI 0.806–0.897; p < 0.001), comparable to Lee/RCRI (AUC 0.860; 95% CI 0.818–0.901; p < 0.001) and higher than AUB-HAS2 (AUC 0.779; 95% CI 0.731–0.826; p < 0.001). Conclusions: PERFORM-CV showed good apparent discrimination in the derivation cohort and may complement established bedside risk tools by incorporating echocardiographic and laboratory data. The ROC-derived thresholds should be interpreted as data-driven derivation cut-offs; resampling-based internal validation and external validation are required before broader clinical use. Full article

Background: Left ventricular global longitudinal strain (GLS) measured by speckle-tracking echocardiography (STE) has become a key marker of myocardial systolic function, yet normal reference values remain heterogeneous, and the magnitude of physiological sex differences is not fully defined. We performed a systematic review and meta-analysis to establish pooled GLS reference estimates in healthy individuals, quantify sex-related differences, and contextualize deformation findings relative to conventional systolic function. Methods: A systematic search of PubMed, Scopus, and EMBASE identified observational studies reporting GLS in healthy adults assessed by two-dimensional or three-dimensional STE. Random-effects meta-analysis using standardized mean differences (SMD) compared GLS between women and men. Descriptive pooled reference values were derived using weighted median and interquartile range (IQR) reconstruction from study-level distributions. Meta-regression analyses explored demographic, clinical, and methodological sources of heterogeneity. A complementary analysis evaluated sex-related differences in left ventricular ejection fraction (LVEF) within the same populations. Results: Thirty-two studies, including 19,157 healthy individuals, were analyzed. The pooled population had a weighted median age of 47.5 years and 53% female participants. Overall, GLS demonstrated a weighted median of 20.3% (IQR 17.8–22.5). Women showed higher GLS values than men (20.8% [18.4–23.1] vs. 19.4% [17.0–21.6]). Meta-analysis of 28 studies confirmed significantly greater GLS in females (SMD 0.487, 95% CI 0.409–0.565; p < 0.001), with consistent findings across imaging modalities and no subgroup interaction. Between-study heterogeneity was substantial (I² = 82.7%), although effect direction was uniform. Meta-regression analyses identified no significant moderators, and sensitivity analyses confirmed stable estimates without publication bias. Segmental analysis demonstrated a physiological base-to-apex strain gradient. In contrast, LVEF was largely comparable between sexes, with no clinically meaningful difference (SMD 0.257, 95% CI 0.186–0.327; p < 0.001), indicating preserved global systolic performance despite differences in myocardial deformation. Conclusions: GLS demonstrates a consistent physiological range in healthy populations, with women exhibiting higher longitudinal deformation than men, independent of the imaging modality. These findings support the adoption of sex-specific GLS reference values and highlight the complementary roles of deformation and volumetric indices in improving the interpretation of myocardial function and reducing misclassification in clinical practice. Full article

Background/Objectives: Acute coronary syndromes (ACS) encompass a spectrum of clinical entities from unstable angina to non–ST-segment elevation myocardial infarction (NSTEMI) and ST-segment elevation myocardial infarction (STEMI), all associated with significant morbidity and mortality. Inflammation plays a central role in the pathophysiology of ACS, contributing to atherosclerotic plaque destabilization, myocardial injury, and adverse clinical outcomes. Inflammatory biomarkers, together with N-terminal pro–B-type natriuretic peptide (NT-proBNP), are increasingly used for risk stratification, yet their prognostic value across different ACS presentations remains unclear. This study aimed to assess the prognostic value of inflammatory status in patients with acute coronary syndromes in a single-center cohort. Methods: This prospective observational study included 100 consecutive patients with ACS and elevated inflammatory biomarkers, enrolled in 2024–2025 at a tertiary cardiovascular center. Inflammatory status was assessed by using C-reactive protein (CRP), neutrophil-to-lymphocyte ratio (NLR) and systemic immune-inflammation index (SII); NT-proBNP was also measured. The primary endpoint was in-hospital MACE, defined as cardiovascular death, recurrent myocardial infarction, stroke, urgent coronary revascularization, or acute heart failure requiring escalation of therapy. Multivariable logistic regression and ROC analyses were performed. Results: Among the 100 ACS patients, half experienced in-hospital MACE. Compared with those without events, patients with MACE were older (p = 0.003) and had higher inflammatory biomarkers—CRP (p < 0.001; strongest association), NLR (p = 0.030), and SII (p = 0.042)—as well as higher NT-proBNP (p = 0.002). Patients with MACE also showed reduced renal function (p < 0.001) and lower left ventricular systolic function, reflected by reduced LVEF (p = 0.001), indicating concomitant renal impairment and ventricular dysfunction. Hypertension was more prevalent in the MACE group (p = 0.028), and new-onset atrial fibrillation was significantly more common among these patients (p < 0.001). In multivariable analysis, LVEF emerged as an independent predictor of short-term outcomes (OR 0.934 per 1% increase; p = 0.047). Conclusions: Inflammatory activation appears closely linked to the occurrence of in-hospital adverse events in patients with acute coronary syndromes. While left ventricular ejection fraction remained an independent determinant of short-term outcomes, inflammatory biomarkers may provide complementary insight into the inflammatory burden accompanying ACS. Full article

Background: Risk stratification in patients with bicuspid aortic valve (BAV) and severe aortic stenosis (AS) remains challenging. Valvulo-arterial impedance (Zva), an integrated marker of global left ventricular (LV) afterload, has shown prognostic value in tricuspid AS; however, data in BAV are limited. This study aimed to evaluate the association of Zva with LV remodeling, symptoms, and all-cause death in patients with BAV and severe AS. Methods: In this retrospective, two-center cohort study, 147 patients with severe AS and BAV were included. Zva was calculated at the time of the first echocardiographic diagnosis of severe AS. The study endpoint was all-cause mortality. Results: Over a median follow-up of 9.8 years, 24 patients (16%) died. A Zva threshold of 5 mmHg/mL/m² was identified as optimal by ROC analysis. Patients with Zva ≥ 5 mmHg/mL/m² showed higher mortality rates (29% vs. 10%; p = 0.003), more advanced symptoms (NYHA III-IV: 41% vs. 9%; p < 0.001), adverse LV remodeling, lower LVEF (60% (IQR 36–66) vs. 66% (IQR 61–71); p = 0.001), and worse LV global longitudinal strain (14.8% ± 2.7 vs. 16.5% ± 3.0; p = 0.016). Zva ≥ 5 mmHg/mL/m² was independently associated with worse long-term survival after adjustment (HR 2.885; 95% CI 1.119–7.438; p = 0.028). Conclusions: Among patients with BAV and severe AS, an increased Zva was associated with more advanced symptoms, adverse LV remodeling, impaired LV systolic function, and worse long-term survival, and might therefore help in risk stratification of these patients. Full article

Heart failure (HF) affects approximately 64 million people globally. HF often coexists with chronic kidney disease. HF may affect the heart during diastolic filling, systolic ejection, or both. Conventionally, HF is categorized by left ventricular ejection fraction (LVEF). One of the leading causes of death in chronic kidney disease (CKD) patients of cardiovascular origin increase hospitalizations and worsen quality of life by causing fluid and electrolyte overload. As kidney function declines, increases risk of development of HF in CKD, with a negative impact and worse prognosis in these patients. This narrative review provides healthcare professionals—including nephrologists, car-diologists, internists, and general practitioners—with evidence-based strategies to iden-tify and manage this complex comorbidity, aiming to reduce hospitalization and mor-tality in CKD patients. By synthesizing recent findings on risk stratification, diagnostic modalities, and individualized treatment—particularly for patients undergoing renal replacement therapy—clinicians can enhance volume management and optimize patient outcomes. Considering the increasing prevalence of chronic kidney disease and associated cardiovascular comorbidities, this review addresses pathogenic mechanisms, diagnostic approaches, pharmacological treatments, and dialytic therapy modifications. Full article

Inflammatory myocardial involvement has been reported in canine leishmaniosis (CanL); however, studies evaluating the degree of myocardial dysfunction in affected dogs are limited. This prospective study aimed to investigate myocardial involvement in dogs with CanL using conventional and speckle-tracking echocardiography (STE), focusing on the assessment of left ventricular systolic function and myocardial strain. Symptomatic, initially untreated dogs with a diagnosis of leishmaniosis and free from other vector-borne diseases or underlying heart diseases were enrolled (Leish group). Healthy dogs matched for age, body weight, breed, and sex were selected for the control group (C group). At the time of inclusion (T0) and at each follow-up, laboratory tests as well as conventional echocardiographic examination and STE were performed. For strain analysis, apical longitudinal long-axis 4-chamber, 3-chamber, and 2-chamber views were used (2C, 3C, 4C, respectively) to obtain the average global longitudinal strain (GLSAV), which is recognised to have the maximum reliability as an indicator of left ventricular dysfunction in humans. The software obtains GLSAV by averaging the longitudinal strain values from all left-ventricular segments derived from the multiple apical views. After enrolment, dogs were treated with a combination of meglumine and allopurinol and were monitored for six months. Clinical-pathological and echocardiographic data were collected at follow-up at 1, 3, and 6 months after the start of treatment (T1, T2, T3) and compared between the two study groups using appropriate statistical tests. Sixteen dogs composed the C group and nine dogs the Leish group. At T0, none of these dogs had abnormalities in cardiac auscultation, plasma cardiac troponin concentration was within the reference range, and standard echocardiographic examination excluded underlying cardiac diseases. The comparison between C and Leish groups did not show a statistically significant difference in any of the strain parameters analysed (GLSAV, GLS4C, GLS3C, GLS2C). Moreover, strain values in the Leish group did not change significantly over time. In conclusion, in this preliminary study on a limited population of dogs with leishmaniosis, both conventional echocardiography and STE failed to reveal clear changes suggestive of left ventricular systolic dysfunction secondary to possible myocarditis or as a consequence of the systemic disease in dogs with active leishmaniosis. However, further STE studies in larger cohorts of dogs with leishmaniosis are needed to confirm and expand our findings. Full article

Obesity is a chronic, highly prevalent disease affecting nearly one-third of the global population and represents a major independent risk factor for heart failure (HF), particularly heart failure with preserved ejection fraction (HFpEF). Excess adiposity—especially visceral and epicardial adipose tissue (EAT)—acts as an active endocrine and immune organ, promoting chronic low-grade inflammation, oxidative stress, endothelial dysfunction, and adverse myocardial remodeling. Expanded EAT exerts both paracrine inflammatory effects and mechanical constraint on the myocardium, contributing to diastolic dysfunction, microvascular impairment, atrial arrhythmogenesis, and elevated filling pressures despite preserved systolic function. Evidence demonstrates a dose–response relationship between increasing body mass index and incident HF. Clinically, obesity-related HFpEF is characterized by concentric left ventricular hypertrophy, impaired relaxation, increased plasma volume, reduced exercise tolerance, and relatively low natriuretic peptide levels, complicating diagnosis. HF management includes traditional treatment with diuretics, renin-angiotensin system inhibitors, β-blockers, mineralocorticoid receptor antagonists, and angiotensin receptor-neprilysin inhibitors. These agents widely remain foundational as they primarily target hemodynamic and neurohormonal pathways in HF. In contrast, sodium–glucose cotransporter 2 inhibitors consistently reduce HF hospitalizations across the ejection fraction spectrum, while glucagon-like peptide-1 receptor agonists and dual incretin therapies (e.g., tirzepatide) promote substantial weight loss, improve symptoms, and demonstrate promising anti-remodeling effects in obesity-related HFpEF. Recognizing obesity-driven HF as a distinct cardiometabolic entity supports an integrated therapeutic strategy combining structured weight reduction with guideline-directed HF polypharmacotherapy to address both hemodynamic burden and upstream adiposity-related mechanisms. Full article

Ischemic cardiomyopathy is defined as coronary artery disease accompanied by left ventricular dysfunction with an ejection fraction equal to or less than 40%. The substrate of ischemic cardiomyopathy is heterogeneous, characterized by the coexistence of normal, stunned, hibernating, and scarred myocardium within the same myocardial region. Altogether, these components may represent different phases of a single pathological process. It is well-established that the assessment of isolated myocardial viability and ischemia alone has failed to reliably guide the indication for coronary artery bypass grafting (CABG). CABG in patients with low ejection fraction carries a significant risk of perioperative mortality and morbidity, largely related to the development of postcardiotomy shock. Preoperative optimization with pharmacologic or mechanical circulatory support (MCS) is often essential; the decision requires integrating multiple complex factors, including clinical presentation, response to optimization therapy, myocardial viability, the presence of hibernating or scarred myocardium, left ventricular end-systolic volume index, coronary angiography findings, hemodynamic assessment, and the Pulmonary Arterial Pressure Index score. A preoperative evaluation that incorporates anatomical, morphological, functional, and hemodynamic domains enables more precise selection and timing of MCS. Preemptive left ventricular unloading mitigates the physiological impact of cardiopulmonary bypass, preserves end-organ perfusion, and reduces the need for high-dose vasopressors. However, the risk–benefit ratio remains uncertain and may be associated with serious complications. Careful judgment regarding the indications for MCS has the potential to enhance the safety of CABG in high-risk patients, but robust, long-term, prospective studies are needed to determine its true impact on clinical outcomes. In this review, we will examine the indications and criteria for the use of MCS in patients with advanced ischemic cardiomyopathy, as well as the various devices available for preoperative or intraoperative support, including technical considerations, advantages and disadvantages, and associated complications. Full article

Background: Severe aortic stenosis (AS) increases left ventricular afterload and disrupts ventricular–vascular coupling. Transcatheter aortic valve replacement (TAVR) promptly relieves valvular obstruction, but its immediate effects on blood pressure-dependent arterial load and ventricular–vascular interactions are not fully clarified. Estimated pulse wave velocity (ePWV), derived from age and mean arterial pressure, is a convenient surrogate of global arterial load. The study aimed to assess ePWV before and after TAVR and its relationship with ventricular function and inflammatory biomarkers. Methods: In this retrospective observational study, 100 elderly patients with severe AS undergoing TAVR underwent detailed clinical, laboratory, and echocardiographic assessments before and after the procedure. Arterial stiffness was quantified using ePWV, while left ventricular geometry and systolic function were evaluated by standard echocardiography. Post-procedural reassessment was performed at hospital discharge (median 8 days after TAVR). Results: TAVR led to a modest but significant reduction in ePWV (from 12.79 ± 1.54 to 12.39 ± 1.54 m/s, p < 0.01) and improvement in left ventricular ejection fraction (LVEF) (from 44.89 ± 9.2% to 46.7 ± 7.95%, p < 0.01). Higher baseline ePWV correlated with unfavorable left ventricular remodeling and systolic dysfunction, and post-procedural ePWV remained linked to right ventricular performance. Before TAVR, ePWV and LVEF were both associated with inflammatory biomarkers, relationships that disappeared after intervention. Conclusions: Overall, ePWV functioned as an integrated measure of ventricular–vascular interaction and global hemodynamic load, though its interpretation post-TAVR requires caution due to direct blood pressure dependence and confounding by acute procedural inflammation. Full article

The role of circulating microRNAs in the pathophysiology of cardiac remodeling in primary hypertension (PH) remains incompletely understood. Left ventricular global longitudinal strain (LV GLS) is a sensitive marker of subclinical systolic dysfunction and can be used to monitor early cardiac involvement in cardiovascular and renal diseases. To the best of our knowledge, this is the first study to demonstrate an association between circulating miR-16 and LV GLS in children. The study aimed to evaluate the expression levels of miR-16-5p, -21-5p, -27a-3p, -27b-3p, -133a-3p, and -145-5p in untreated children with PH and examine their associations with LV GLS. 50 children with PH and 57 normotensive controls were evaluated for circulating microRNA expression levels and echocardiographic parameters, including LV GLS. Comprehensive anthropometric, biochemical, blood pressure, and arterial indices were also assessed. Among the analyzed microRNAs, miR-16-5p exhibited a positive association with LV GLS (R = 0.305, p = 0.031), whereas miR-27b-3p demonstrated a negative association (R = −0.330, p < 0.001). Compared with controls, hypertensive children exhibited significantly higher (i.e., less negative) LV GLS (r = 0.29, p = 0.002), indicating early systolic dysfunction occurring already at an early stage of the disease. In conclusion, these findings support the idea that specific microRNAs might play a differential role in early myocardial functional alterations in pediatric PH. Higher miR-16 expression levels may be associated with impaired myocardial deformation, potentially reflecting its involvement in early maladaptive myocardial remodeling. Furthermore, LV GLS may represent a sensitive and clinically informative marker of early myocardial dysfunction beyond traditional echocardiographic parameters in this population. Full article