Maria Carmo Pereira Nunes

Infective endocarditis (IE) is characterized by systemic inflammation, yet the contribution of cytokine network dysregulation to clinical outcomes remains poorly understood. We aimed to evaluate cytokine co-expression patterns in IE and identify immune network signatures associated with in-hospital mortality and major complications. We conducted a prospective cohort study of adult patients hospitalized with IE at a quaternary public hospital in Brazil (2012–2024). Serum cytokines and chemokines were measured at one to three time points during hospitalization. Weighted topological overlap (wTO) and Co-expression Differential Network Analysis (CoDiNA) were used to characterize cytokine interactions in baseline. Logistic mixed-effects models assessed associations between individual cytokines and in-hospital mortality. Of 305 screened patients, 160 met inclusion criteria (41 deaths; in-hospital mortality 25.6%). Survivors exhibited dense, integrated cytokine interaction networks, whereas non-survivors showed markedly fragmented networks with loss of connectivity across multiple cytokines. IFN-γ and IL-1RA formed a preserved but isolated axis in fatal cases, while IL-7 displayed outcome-specific connectivity in patients with infectious complications. A distinct triad involving IFN-γ, IL-1RA, and IL-6 differentiated patients with cardiac complications. In multivariable models adjusted for age, sex, and sampling time, CCL2 was independently associated with in-hospital mortality. Immune network disruption is strongly associated with adverse outcomes in IE. Distinct cytokine signatures, including altered interactions of IFN-γ, IL-1RA, IL-6, IL-7, and CCL2, identify high-risk patients and reveal potential biological pathways underlying clinical deterioration.

In severe rheumatic mitral stenosis (MS), left ventricular (LV) systolic function is often considered preserved based on ejection fraction. However, longitudinal myocardial mechanics may be impaired and may improve after relief of inflow obstruction. The regional pattern of strain recovery following percutaneous mitral balloon valvuloplasty (PMBV), and its prognostic implications remain uncertain. To characterize global and regional LV strain response following PMBV, identify determinants of limited strain recovery, and evaluate its association with long-term outcomes. In 190 patients with severe symptomatic MS undergoing PMBV, LVGLS was measured by speckle-tracking echocardiography before and within 48 h after intervention. Absence of meaningful recovery was defined as ≤ 15% relative GLS improvement. The secondary endpoint was cardiovascular death or subsequent mitral valve replacement. PMBV significantly increased mitral valve area and reduced transmitral gradients, with concomitant improvement in GLS despite unchanged ejection fraction. Strain recovery demonstrated a distinct basal-to-apical gradient, with the greatest improvement in basal segments. In 29% of patients, absent GLS improvement was observed. Limited recovery was independently associated with larger baseline valve area, reduced leaflet displacement, lower pre-procedural left atrial pressure, and higher post-procedural pulmonary artery pressure. Over 48 months of follow-up, adverse outcomes were independently predicted by age, advanced NYHA class, smaller post-procedural valve area, higher residual gradient, and greater mitral regurgitation severity. Absence of GLS improvement was not associated with long-term events. In severe rheumatic MS, PMBV leads to an immediate improvement in LV longitudinal mechanics, characterized by a distinct basal predominance of recovery. This response appears largely load-mediated and does not independently translate into improved prognosis, which is primarily determined by procedural success and the degree of residual valve obstruction.

BACKGROUND: Chagas disease (ChD), a neglected cardiovascular condition, affects 7.5 to 10.5 million people worldwide. Opportunistic screening during routine electrocardiography may allow earlier detection of unrecognized infections, enabling timely antiparasitic therapy or optimized cardiac care. This study prospectively evaluated the feasibility and diagnostic accuracy of an artificial intelligence (AI)–enabled ECG model enriched with 3 epidemiological questions (AI-ECG-EPI model) as an opportunistic screening for ChD in endemic regions of Brazil. METHODS: We conducted a prospective study embedded in the Telehealth Network of Minas Gerais, Brazil, across 107 municipalities in hyperendemic and endemic regions. From October 2023 to September 2024, adults undergoing routine tele-ECGs were eligible. The primary exposure was the output of the AI-ECG-EPI model: all positive individuals and a 3:1 sample of negative individuals were invited for serology (index test–dependent sampling), the reference standard. Weighted analyses (inverse probability) accounted for this sampling design. Diagnostic metrics included sensitivity, specificity, predictive values, likelihood ratios, area under the receiver operating characteristics curve, and area under the precision recall curve. The AI-ECG-EPI model was compared with both an epidemiological questions model and an AI ECG–only model. RESULTS: Among 75 779 eligible ECGs, the AI-ECG-EPI model was available for 59 154 individuals; 6812 (11.5%) screened positive. A total of 7804 selected were invited for serology, and 3509 completed testing (2517 positive; 992 negative). ChD was confirmed in 36.8% of positive and 9.3% of negative individuals. The weighted prevalence of ChD was 12.2%. Sensitivity was 34.3%, specificity 91.6%, harmonic mean of precision and recall score 0.52, and diagnostic odds ratio 5.69. The AI-ECG-EPI model showed higher discrimination than both the epidemiological questions model and AI ECG–only model (area under the receiver operating characteristics curve, 77.6% versus 70.0% and 64.5%, respectively; P <0.001). Precision recall curves showed higher precision across most recall levels. Exploratory analysis suggested improved risk reclassification (net reclassification improvement, 0.503). Performance was higher in women and in individuals with Chagas cardiomyopathy. CONCLUSIONS: In this community-based study, an AI-ECG-EPI model integrated into a public telecardiology network enabled feasible opportunistic screening for ChD in primary care. It showed acceptable diagnostic accuracy, with higher discrimination than epidemiological questions and AI ECG–only models, and identified many previously undiagnosed patients in endemic regions, supporting its potential role in scalable screening strategies. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02646943.

Objective: Apical aneurysm is a hallmark of Chagas cardiomyopathy (CCM) and has long been implicated in thromboembolic complications. However, its independent contribution to cardioembolic (CE) stroke and the mechanisms underlying this association remain incompletely understood. This study evaluated the association between apical aneurysm and CE stroke and assessed the prognostic implications of CE stroke in patients with CCM. Methods: In this prospective cohort study, 518 patients with confirmed CCM were enrolled at a tertiary referral centre between 2007 and 2022. Baseline evaluation included clinical assessment, electrocardiography and echocardiography. Ischaemic stroke subtype was classified using the Causative Classification System. Logistic regression analyses examined factors associated with CE stroke. Genetic matching was used to assess the association between apical aneurysm and CE stroke while causal mediation analysis evaluated the contribution of left ventricular (LV) thrombus. Cox proportional hazards models assessed factors associated with all-cause mortality or heart transplantation. Results: At enrolment, 73 patients (14.1%) had a history of CE stroke. In multivariable analyses, New York Heart Association (NYHA) functional class III/IV, lower LV ejection fraction and LV thrombus were independently associated with prior CE stroke, whereas apical aneurysm was not. However, matched analyses demonstrated a significant association between apical aneurysm and CE stroke, of which 63.3% was mediated through LV thrombus formation. During a mean follow-up of 4.9 years, 174 patients died and 22 underwent heart transplantation. NYHA functional class III/IV, right-sided heart failure, left atrial enlargement and lower LV ejection fraction were independently associated with the composite outcome of death or heart transplantation, whereas neither prior CE stroke nor apical aneurysm was associated with adverse outcomes. Incident CE stroke occurred in 41 patients (9%) and was independently associated with prior CE stroke and LV thrombus. Conclusion: In CCM, CE stroke is primarily driven by LV thrombus formation. Apical aneurysm increases embolic risk mainly through thrombus mediation, while prior CE stroke identifies patients at increased risk for recurrence. These findings support targeted stroke prevention strategies focused on thrombus detection and anticoagulation.

Background: Rheumatic heart disease (RHD) remains a major cause of morbidity and mortality in low-resource settings, underscoring the need for accurate and scalable screening approaches. The 2023 World Heart Federation (WHF) screening criteria were designed to facilitate task-shifting but real-world performance data are limited. We evaluated the diagnostic accuracy and operational performance of the 2023 WHF criteria in a large school-based screening programme in Uganda. Methods: We conducted a cross-sectional diagnostic accuracy study among 11 198 children aged 5–17 years screened between September and November 2024 in Lira District, Northern Uganda. All screen-positive children (n=522) and a stratified random sample of screen-negative children (n=3301) underwent confirmatory echocardiography. The index test was nurse-performed handheld echocardiography using a standardised three-view protocol. The reference standard was comprehensive echocardiography interpreted by a blinded expert adjudication panel using full WHF criteria. Diagnostic accuracy metrics included sensitivity, specificity, positive and negative predictive values and likelihood ratios. Partial verification bias was addressed using multiple imputation. Results: Among 3802 participants who had the reference standard test and no alternative cardiac diagnosis, 122 cases of RHD were identified. After accounting for partial verification bias, sensitivity was 60.0% (95% CI 46.6 to 73.5%) and specificity 96.3% (95% CI 96.0 to 96.7%). Positive and negative predictive values were 19.5% and 99.4%, respectively. Complete-case analysis overestimated sensitivity (80.3%) and underestimated specificity (89.0%). Missed cases were predominantly early-stage or aortic valve disease, with no advanced cases missed. Exploratory analysis using single-expert interpretation yielded comparable performance. Conclusions: In this large real-world evaluation, nurse-performed handheld echocardiographic screening using the 2023 WHF criteria demonstrated high specificity and negative predictive value, supporting its role as a scalable frontline triage strategy for RHD. After accounting for partial verification bias, sensitivity was moderate, with missed cases representing early-stage disease, highlighting opportunities to improve case detection through optimisation of screening workflows, training and technology.

Introduction: Acute rheumatic fever (ARF) remains a leading cause of pediatric cardiovascular morbidity and a major driver of rheumatic heart disease (RHD) in low- and middle-income countries. Early identification of children at highest risk for adverse outcomes is essential to guide timely management and referral, but remains challenging in resource-limited settings. This study aimed to characterize the clinical profile of pediatric ARF and identify readily available predictors of adverse outcomes in a high-endemic region of Brazil. Methods: We conducted a cohort study of children treated for ARF at a tertiary pediatric center in Feira de Santana, Brazil, between 2010 and 2023, including both retrospectively identified cases and a prospectively enrolled subset through the Acute Rheumatic Fever Diagnosis Collaborative (ARC) Network. Clinical, laboratory, treatment, and outcome data were obtained from hospital and outpatient records. The primary outcome was a composite of cardiac surgery or death. Independent predictors were identified using multivariable logistic regression with covariate selection based on clinical relevance and model parsimony. Model performance was assessed using discrimination (C-statistic) and risk reclassification metrics. Results: A total of 151 children were included (median age, 9 years; 46% female). Carditis was present in 76%, with moderate-to-severe involvement in 49%, predominantly affecting the mitral valve. During a median follow-up of 17.5 months, 20 children (13%) experienced the primary outcome. In multivariable analysis, absence of fever (OR 0.14, 95% CI 0.31–0.65), higher ESR (OR 1.04 per mm/h, 95% CI 1.01–1.07), and lower hematocrit (OR 0.85, 95% CI 0.74–0.98) were independently associated with adverse outcomes. Incorporating erythrocyte sedimentation rate (ESR) into the model improved risk prediction, with a net reclassification improvement (NRI) of 0.79 ( P = 0.005) and an integrated discrimination improvement (IDI) of 0.11 ( P = 0.032). The final model demonstrated good discrimination (C-statistic 0.82). Results were consistent after multiple imputation. Conclusions: In children with ARF, simple inflammatory and hematologic markers are independently associated with progression to severe outcomes. ESR, an inexpensive and widely accessible test, provides incremental prognostic information and may support scalable risk stratification strategies aimed at reducing progression to advanced RHD in resource-limited endemic settings.