BACKGROUND: Management of hypertension (HTN) in obstructive hypertrophic cardiomyopathy (oHCM) is challenging because blood pressure (BP)-directed therapies may exacerbate left ventricular outflow tract (LVOT) obstructio...BACKGROUND: Management of hypertension (HTN) in obstructive hypertrophic cardiomyopathy (oHCM) is challenging because blood pressure (BP)-directed therapies may exacerbate left ventricular outflow tract (LVOT) obstruction. Cardiac myosin inhibitors (CMIs), such as mavacamten, reduce hypercontractility and LVOT gradients, but management of concomitant BP-directed therapies in routine practice remains uncertain. METHODS: We conducted a retrospective single-center cohort study of adults with oHCM treated with mavacamten. Patients were stratified by pre-existing HTN status, with clinical, medication, BP, and echocardiographic data collected at baseline and approximately three months. BP-directed therapies included renin-angiotensin system inhibitors, mineralocorticoid receptor antagonists, and diuretics. Beta-blockers and calcium channel blockers were described separately because of their common use for LVOT obstruction, symptom control, or arrhythmia/rate control. RESULTS: Among 34 patients, 23 (67.6%) had pre-existing HTN. At three months, BP-directed therapies among patients with HTN included renin-angiotensin system inhibitors in 11, mineralocorticoid receptor antagonists in 11, and diuretics in 4; no patient without baseline HTN received BP-directed therapy. LVOT gradients decreased significantly in the HTN and non-HTN groups, from 77.1 to 27.0 mmHg and from 66.3 to 19.3 mmHg, respectively (both p < 0.05). Systolic and diastolic BP remained stable in both groups, and no patient developed incident HTN. CONCLUSION: Following mavacamten initiation, LVOT gradients improved and BP remained stable in patients with and without HTN. These findings suggest that individualized BP management is feasible during CMI therapy and support prospective evaluation.
BACKGROUND: Kawasaki disease (KD) is associated with various myocardial injuries, including myocardial perfusion abnormality. This study aims to assess the distribution of myocardial perfusion abnormality in patients wit...BACKGROUND: Kawasaki disease (KD) is associated with various myocardial injuries, including myocardial perfusion abnormality. This study aims to assess the distribution of myocardial perfusion abnormality in patients with KD and explore their relationships with left ventricular (LV) remodeling. METHODS: This prospective single-center study enrolled children with KD who underwent fully quantitative CMR rest perfusion. Myocardial blood flow (MBF) was measured and corrected based on the heart rate-blood pressure product (MBFcor). Statistical analyses included ANOVA, Pearson correlation and multivariate linear regression. RESULTS: Eighty-seven patients with KD (mean age, 7.5 ± 2.2 years) and 33 age- and sex-matched controls (mean age, 8.2 ± 2.8 years) were included. Global MBFcor was lower in patients than in controls, especially among patients during the acute phase. Subgroup analysis showed that patients with Z score ≥ 5 had significant decreases in global MBFcor, as well as regional MBFcor in the territories of the left anterior descending artery (LAD) and left circumflex artery (LCX) (p < 0.05 for all). Global MBFcor and regional MBFcor in the territories of the LAD and LCX were correlated with Z score among patients with KD. Covariate-adjusted multivariable regression analyses demonstrated that Z score and the acute phase were independently associated with global MBFcor. Furthermore, global MBFcor was negatively associated with increased LV mass index. CONCLUSIONS: Fully quantitative CMR rest first-pass perfusion revealed decreased myocardial perfusion in children with KD. Z score and the acute phase were independently associated with decreased myocardial perfusion; decreased MBFcor was associated with LV mass index.
BACKGROUND: Medication non-adherence is a major challenge in stroke prevention in atrial fibrillation (AF), yet no validated tool exists to identify patients at risk of non-adherence at the time of oral anticoagulation (...BACKGROUND: Medication non-adherence is a major challenge in stroke prevention in atrial fibrillation (AF), yet no validated tool exists to identify patients at risk of non-adherence at the time of oral anticoagulation (OAC) initiation. METHODS: In this retrospective cohort study at a large tertiary centre in New York City (2015-2023), adults with AF and a CHA₂DS₂-VASc score ≥ 2 initiating OAC were included. Predicted medication adherence was quantified using the Medication Adherence Score (MAS), a validated algorithm incorporating demographic, socioeconomic, and geographic attributes, dichotomised as high (MAS ≥80) or low (MAS <80). The primary outcome was ischaemic stroke within 12 months, analysed using Fine-Gray competing-risk regression. RESULTS: Of 11,233 eligible patients, 4035 (35.9%) had high and 7198 (64.1%) had low predicted adherence. Most patients received a direct oral anticoagulant (DOAC, 70.3%), 10.7% received warfarin, and 19.0% switched agents. Ischaemic stroke occurred in 6.2% of patients. High predicted adherence was associated with significantly lower stroke risk (sHR 0.67; 95% CI 0.56-0.80), with 12-month cumulative incidences of 5.08% vs. 7.97%. Continuously modelled MAS confirmed a dose-response relationship (HR 0.98 per unit increase; 95% CI 0.97-0.99). Results were consistent after excluding patients with prior stroke (sHR 0.66; 95% CI 0.53-0.83). CONCLUSIONS: In AF patients initiating OAC, low predicted medication adherence is independently associated with increased ischaemic stroke risk. The MAS may support early identification of high-risk patients, enabling targeted adherence interventions at OAC initiation.
BACKGROUND: Severe tricuspid regurgitation (TR) is increasingly recognized as a major determinant of outcomes, yet its mechanistic trajectory under contemporary medical therapy remains insufficiently defined. OBJECTIVES:...BACKGROUND: Severe tricuspid regurgitation (TR) is increasingly recognized as a major determinant of outcomes, yet its mechanistic trajectory under contemporary medical therapy remains insufficiently defined. OBJECTIVES: To characterize the longitudinal evolution of severe TR managed conservatively and to define a reproducible congestion-right ventricle-renal phenotype associated with clinical outcomes. METHODS: We conducted a longitudinal observational cohort including 40 consecutive patients with at least severe TR. Serial assessments at baseline and 6, 12, 18, and 24 months included clinical status, echocardiography, biomarkers, and treatment data. The primary endpoint was a composite of heart failure hospitalization or all-cause death. Associations between right ventricular (RV) function, NT-proBNP, diuretic intensity, and renal function were evaluated. RESULTS: Patients were elderly (78.5 ± 5.5 years), predominantly female, with atrial functional TR (95%) and atrial fibrillation (93%). Persistent congestion was observed throughout follow-up, with sustained high-dose diuretic use (≥80 mg/day in 57.5% at baseline, remaining stable over time). Renal function declined progressively (eGFR 50.2 ± 10 to 43.5 ± 11 mL/min/1.73 m; p < 0.01), while NT-proBNP increased significantly (median ~ 1700 to >3000 pg/mL; p < 0.01). During longitudinal follow-up, recurrent heart failure events and progressive renal impairment were frequently observed. Renal impairment and diuretic intensity were independently associated with adverse outcomes. Strong correlations linked RV dysfunction, biomarker activation, diuretic burden, and renal decline. CONCLUSIONS: Severe TR follows a structured, congestion-driven trajectory linking venous congestion, RV dysfunction, renal impairment, and clinical events. This study defines a reproducible cardiorenal phenotype and supports earlier, mechanism-based intervention strategies.
BACKGROUND: Ischemic heart disease (IHD) presents a growing global health burden across diverse geographic and socioeconomic settings. Clinical practice guidelines are typically developed by professional societies in hig...BACKGROUND: Ischemic heart disease (IHD) presents a growing global health burden across diverse geographic and socioeconomic settings. Clinical practice guidelines are typically developed by professional societies in high-income countries, often with limited consideration of implementation barriers in other healthcare settings. We sought to understand clinicians' use of IHD guidelines in their practice, perceived deficiencies, implementation barriers, and differences between doctors practicing in high-income countries (HIC) or in low-/middle-income countries (LMIC). METHODS: An internet-based, international survey of physicians treating patients with IHD, (July 26, 2025-November 15, 2025), inquiring about participants' demographics, experience, and views of IHD guidelines as related to their practice. RESULTS: Responses were provided by 587 clinicians from 97 countries. Approximately half (51.8%) considered the IHD guidelines as mostly or fully applicable in their country, a view more preponderant in HIC (67.3%) than in LMIC (48.8%; p = 0.0125). Most (63.2%) thought IHD guidelines were highly applicable in HIC, but only 9.0% deemed the same for LMIC. The greatest barriers to guideline implementation were their being mostly relevant for HIC (72%), and cost, with the latter selected more frequently by the LMIC than the HIC group (61.7% v 20.4%; p < 0.00001). Desires for future guidelines included availability in digital format, and inclusion of co-authors from LMIC. CONCLUSIONS: Survey respondents indicated that current IHD guidelines do not address the needs of clinicians and patients in LMIC as effectively as they do for those in HIC. Respondents advocated for future guidelines to have specific recommendations for differing socio-economic environments, and consideration of cost reimbursement.
BACKGROUND: In patients with hypertrophic cardiomyopathy (HCM), identifying the underlying mechanism of unexplained syncope is crucial for preventing sudden cardiac death (SCD) and managing recurrences. We evaluated the...BACKGROUND: In patients with hypertrophic cardiomyopathy (HCM), identifying the underlying mechanism of unexplained syncope is crucial for preventing sudden cardiac death (SCD) and managing recurrences. We evaluated the effectiveness of a novel stepwise diagnostic algorithm for the etiological assessment of syncope in a clinical HCM cohort. METHODS: We retrospectively applied the algorithm to consecutive HCM patients with unexplained syncope referred to the Syncope or Cardiomyopathy Units at Careggi University Hospital (Florence, Italy) between May 2004 and July 2024. RESULTS: Among 43 patients (mean age 54.9 ± 17.4 years; 56% male), the cause of syncope was identified at Step 1 (initial evaluation) in 22 cases (51.2%): hypotensive in 18 and arrhythmic in 4. An obstructive mechanism (LVOTO) was the primary cause in 1 additional case (2.3%). Autonomic assessment (Step 3: Tilt Testing, Carotid Sinus Massage, and ABPM) provided diagnostic findings in 11 patients (25.5%). Implantable Loop Recorders (ILR, Step 4) were deployed in 13 patients (30.2%), revealing significant asystole in 2 (15.3%) and excluding arrhythmia in 1 (7.6%) during recurrences. Overall, the algorithm established a diagnosis in 88.3% of cases. Over a mean follow-up of 82.8 ± 50.6 months, no SCD occurred; 6 patients received an ICD. CONCLUSION: A structured, stepwise diagnostic approach clarified the cause of syncope in nearly 90% of HCM patients, potentially optimizing long-term risk stratification and reducing unnecessary device implantation.
BACKGROUND: Identifying patients with nonischemic dilated cardiomyopathy (NIDCM) who are at increased risk for life-threatening ventricular arrhythmias remains a clinical challenge. The Fibrosis-4 (FIB-4) index, a noninv...BACKGROUND: Identifying patients with nonischemic dilated cardiomyopathy (NIDCM) who are at increased risk for life-threatening ventricular arrhythmias remains a clinical challenge. The Fibrosis-4 (FIB-4) index, a noninvasive marker originally developed to evaluate liver fibrosis, has been shown to be associated with increased risk of adverse events in several cardiovascular diseases. This study aimed to investigate the relationship between FIB-4 levels and arrhythmic risk in patients diagnosed with NIDCM. METHODS: A total of 1233 consecutive patients with NIDCM (714 men; 59.6 ± 12.4 years) were evaluated. The primary endpoint was the composite major arrhythmic event, including sudden cardiac death (SCD), documented sustained ventricular tachycardia or fibrillation, or appropriate implantable cardioverter defibrillator (ICD) therapy. Cardiovascular death and all-cause death were also evaluated as the secondary endpoints. RESULTS: During a median follow-up period of 70 months (interquartile range: 60 to 85 months), the primary endpoint was developed in 367(29.8%) patients. ROC analysis showed that using a cut-off level of 1.67, FIB-4 predicted the occurrence of the composite primary endpoint with a sensitivity of 66% and specificity of 81%. On multivariate analysis, after adjusting for other confounding factors, FIB-4 ≥ 1.67 remained independently associated with arrhythmic risk (HR: 4.88, 95% CI: 3.92-6.07, p < 0.001). CONCLUSIONS: This study showed that the FIB-4 index is an independent predictor of major arrhythmic events and death in patients with NIDCM. As a readily available index, FIB-4 may offer additional value in identifying high-risk patients who may benefit from closer monitoring or prophylactic interventions in this patient population.
Martini M, Masini M, Rigato I
… +13 more, Parodi A, Brizzi LF, Iezzi L, Marra MP, De Gaspari M, Pinci S, Cecere A, Celeghin R, Marinas MB, Basso C, Corrado D, Pilichou K, Bauce B
Int J Cardiol
· 2026 Jun · PMID 42372975
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BACKGROUND: Arrhythmogenic cardiomyopathy (ACM) is a genetic heart muscle disease primarily associated with life-threatening ventricular arrhythmias. Improved arrhythmic risk stratification and therapies have enhanced su...BACKGROUND: Arrhythmogenic cardiomyopathy (ACM) is a genetic heart muscle disease primarily associated with life-threatening ventricular arrhythmias. Improved arrhythmic risk stratification and therapies have enhanced survival, making heart failure (HF) an increasingly relevant clinical issue. This study aims to characterize HF in ACM patients and identify variables associated with its occurrence. METHODS: This retrospective, single-center study included 657 ACM patients diagnosed according to the 2010 Revised Task Force Criteria and Padua criteria. HF was defined as hospitalization due to HF symptoms. Clinical, electrocardiographic, imaging and genetic data were compared between patients with and without HF. RESULTS: HF occurred in 48 patients (7.3%). Those with HF were more often probands (p = 0.007) and showed more ECG abnormalities, including T-wave inversions in right (p = 0.004) and lateral leads (p < 0.001) and low QRS voltages in precordial and peripheral leads (p < 0.001). Genetic analysis revealed a higher prevalence of Desmoplakin (DSP) (p = 0.03) and Desmin (p = 0.002) genetic variants. Imaging showed increased ventricular volumes and reduced biventricular systolic function (p < 0.001). The arrhythmic burden was also higher (p = 0.022). Variables associated with HF occurrence were DSP genetic variants (OR = 3.08, p = 0.01), low QRS voltages in peripheral leads (OR = 3.76, p = 0.002), and reduced left ventricular ejection fraction (EF) (OR = 0.89, p < 0.001) and right ventricular EF (OR = 0.93, p < 0.001). CONCLUSIONS: HF in ACM reflects a more severe phenotype with biventricular dysfunction and high arrhythmic burden. Genetic (DSP), electrocardiographic, and imaging markers may contribute to early identification of patients at higher risk and support earlier intervention strategies.
Maggioni AP, Orso F, Lucci D
… +2 more, De Luca L, Colivicchi F
Int J Cardiol
· 2026 Jun · PMID 42361988
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BACKGROUND AND AIM: Randomised clinical trials (SELECT and SOUL) demonstrated that semaglutide, a GLP-1 receptor agonist, reduces the combined outcome measure of atherothrombotic events or cardiovascular mortality in pat...BACKGROUND AND AIM: Randomised clinical trials (SELECT and SOUL) demonstrated that semaglutide, a GLP-1 receptor agonist, reduces the combined outcome measure of atherothrombotic events or cardiovascular mortality in patients with coronary artery disease, both with and without diabetes. Because real-world populations may differ from trial cohorts, we assessed the proportion of patients potentially eligible for semaglutide using the criteria set out by the regulatory authorities based on the SELECT and SOUL results. METHODS AND RESULTS: Patients whose clinical characteristics were comparable to those of patients enrolled in the SELECT and SOUL trials were identified within the START and BRING-UP prevention registries. Among 12,430 patients, 623 were excluded because of severe renal impairment or ongoing GLP-1 receptor agonist therapy. The final population included 11,807 patients: 8682 without diabetes and 3125 with diabetes. Among non-diabetic patients, 3689 (42.5%) were SELECT-like, defined as overweight or obese individuals with established coronary disease. Among diabetic patients, 3059 (97.9%) were SOUL-like, defined as individuals aged ≥50 years with cardiovascular disease. Overall, 6748 of 12,430 patients (54.3%) theoretically fulfilled eligibility criteria for semaglutide treatment in real-world cardiology practice. CONCLUSIONS: According to the criteria set out by the regulatory authorities based on the SELECT and SOUL trial results, a large proportion of patients with coronary artery disease managed by cardiologists may be potentially eligible for semaglutide therapy. Identifying the target population for this therapeutic strategy may help clinicians and healthcare authorities estimate unmet clinical needs and evaluate the sustainability of innovative approaches for secondary cardiovascular prevention.
Simioni L, Loureiro T, Faucherre Y
… +9 more, Cioffi GM, Jelisejevas J, Bennar W, Beretta GS, Puricel S, Meier P, Togni M, Cook S, Skalidis I
Int J Cardiol
· 2026 Jun · PMID 42361987
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BACKGROUND: Obesity is increasing in all regions of Switzerland. Multiple studies have described the "obesity paradox" suggesting a protective effect of obesity on the occurrence of major adverse cardiovascular events (M...BACKGROUND: Obesity is increasing in all regions of Switzerland. Multiple studies have described the "obesity paradox" suggesting a protective effect of obesity on the occurrence of major adverse cardiovascular events (MACE) after ST-segment elevation myocardial infarction (STEMI) treated with percutaneous coronary intervention (PCI). OBJECTIVE: This study aimed to assess the impact of obesity on MACE in STEMI patients undergoing PCI. METHODS: We analyzed data from the Fribourg STEMI Fast-Track prospective registry in a retrospective, single-center cohort study. Adult patients were classified as obese (BMI ≥ 30 kg/m) or non-obese (BMI < 30 kg/m) and followed for 12 months. The primary endpoint was a composite MACE including all-cause death, recurrent acute coronary syndrome (ACS) (STEMI, NSTEMI and unstable angina (UA)), stroke, stent thrombosis, unscheduled revascularisation, and major bleeding (BARC 3-5). Secondary endpoints included stratification according three obesity stages to evaluate 1-year MACE-free survival, as well as assessment of individual MACE components, delays in care, mode of presentation, and clinical and procedural characteristics. Kaplan-Meier analysis with log-rank testing and Cox regression were used to evaluate outcomes. RESULTS: A total of 1043 patients were included between June 2008 and October 2025, of whom 214 (21%) were obese and 829 (79%) were non-obese. Obese patients were slightly younger (60.00 (53.00, 70.00) vs 62.00 (53.00, 72.00) years, p = 0.037), with a similar proportion of women (21% vs 25%, p = 0.299). At 12 months, MACE-free survival was similar between groups (log-rank p = 0.76), and obesity was not associated with MACE after adjustment. No differences were observed in individual components of the composite endpoint. Pre-hospital delay was comparable, whereas first medical contact-to-revascularisation (FMC-to-REVASC) time was longer in obese patients (0.78 vs 0.57 h, p < 0.001), with no difference in total ischemic time. Obese patients were less likely to present via ambulance (31% vs 38%) and more likely to self-present to the emergency department (32% vs 24%; p = 0.037). Clinical presentation, procedural characteristics, and coronary anatomy were similar between groups. CONCLUSIONS: In this contemporary STEMI cohort, obese patients treated with primary PCI did not experience higher 1-year MACE rates than non-obese patients. However, obesity was associated with differences in care pathways and longer in-hospital delays, without impact on clinical outcomes.
Meucci MC, Pontecorvo S, Di Brango C
… +9 more, Lillo R, Iannaccone G, Luigetti M, Recupero C, Locorotondo G, Lanza GA, Lombardo A, Burzotta F, Graziani F
Int J Cardiol
· 2026 Jun · PMID 42349692
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BACKGROUND: Left atrioventricular coupling index (LACI) has emerged as a powerful marker of cardiac remodeling across a variety of cardiac diseases, however its prognostic value in the setting of transthyretin amyloid ca...BACKGROUND: Left atrioventricular coupling index (LACI) has emerged as a powerful marker of cardiac remodeling across a variety of cardiac diseases, however its prognostic value in the setting of transthyretin amyloid cardiomyopathy (ATTR-CM) remains largely unexplored. METHODS: Patients with ATTR-CM who underwent prospective evaluation comprising full echocardiographic assessment between 2021 and 2025 were included. LACI was measured as the ratio between the left atrial (LA) and the left ventricular (LV) end-diastolic volumes. The population was stratified based on LACI terciles. The study endpoint was all-cause mortality. RESULTS: A total of 202 patients (median age 80 years, 80% male) were included, with a predominance of wild-type subtype (70%). LACI terciles cutoffs were: ≤59.5% (first tercile), from 59.5% to 88.1% (second tercile) and > ≥88.1% (third tercile). Higher LACI terciles were associated with a greater prevalence of wild-type disease and atrial fibrillation (AF) and more advanced NAC stage. Higher LACI terciles were associated with significantly smaller LV volumes and larger LA volumes, as well as worse parameters of LV systolic and diastolic function. Three-year survival rates progressively declined across increasing LACI terciles (97%, 68% and 55%, p < 0.001). LACI demonstrated higher discriminatory power for predicting 3-year mortality (AUC 0.789, 95% CI 0.717-0.861), in comparison to LA dimensional parameters. After adjusting for age, NAC stage, AF and LV longitudinal strain, LACI terciles remained significantly associated with all-cause mortality (adjusted HR 1.942, 95% CI 1.078-3.499; p = 0.027). CONCLUSIONS: In patients with ATTR-CM, increasing LACI is associated with markers of disease severity and worse long-term survival.
Lenselink C, Lau YH, Huang W
… +9 more, Ewe SH, Chiong SC, Ng CT, Ricken K, Lipsic E, Voors A, Lam CSP, Yeo KK, Yap J
Int J Cardiol
· 2026 Oct · PMID 42331183
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BACKGROUND: Early risk stratification in patients after acute myocardial infarction (AMI) is critical for guiding therapy and resource allocation. While left ventricular ejection fraction (LVEF) is routinely assessed by...BACKGROUND: Early risk stratification in patients after acute myocardial infarction (AMI) is critical for guiding therapy and resource allocation. While left ventricular ejection fraction (LVEF) is routinely assessed by echocardiography, novel markers offer additional prognostic utility but are not widely assessed due to time constraints or limited expertise. Artificial intelligence (AI) enables rapid, fully automated analysis of echocardiograms, producing standardized, comprehensive measurements. We evaluated the utility of AI-derived echocardiographic parameters on top of clinical variables in predicting outcomes post-AMI. METHODS: Consecutive AMI patients undergoing invasive coronary angiogram were included. Echocardiograms were analyzed using Us2.ai software. Independent predictors of one-year all-cause mortality and major adverse cardiac events (MACE) were assessed using Cox regression. Clinical, echocardiographic, and combined models were compared. RESULTS: Among 1001 patients, aged 64 years (54, 72) and predominantly male (78.1%), 161 (16.1%) died during follow-up. AI-echocardiographic markers independently associated with one-year all-cause mortality or MACE included lower LVEF, greater LV wall thickness, lower LV mass, greater LA area, lower LA reservoir strain and lower aortic valve area. For one-year mortality, the combined model demonstrated superior discrimination compared with the clinical model alone (AUC 0.85 vs. 0.81; p = 0.018). Similarly, for one-year MACE, the combined model showed improved discrimination compared with the clinical model (AUC 0.80 vs. 0.74; p < 0.001) and yielded the lowest Akaike's and Bayesian Informations. CONCLUSION: Combining AI-derived echocardiographic parameters, together with traditional clinical risk factors, provides incremental prognostic value post-AMI. AI tools that automate complex assessments accurately and reproducibly may enhance risk stratification.
Int J Cardiol
· 2026 Jun · PMID 42331182
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AIMS: Diseases of the aorta are driven by chronic inflammation and matrix metalloproteinase activity. Vaccines such as Yellow Fever (YF) and BCG may be associated with vascular protection through "trained immunity", epig...AIMS: Diseases of the aorta are driven by chronic inflammation and matrix metalloproteinase activity. Vaccines such as Yellow Fever (YF) and BCG may be associated with vascular protection through "trained immunity", epigenetic reprogramming of innate immune cells that attenuates systemic inflammatory responses. We investigated the association between population-level vaccination coverage and aortic mortality using contemporary causal inference methods. METHODS AND RESULTS: This ecological study analyzed 27 Brazilian states over 29 years (1994-2022), encompassing 783 state-year observations and 185,429 deaths. Poisson fixed-effects models with state and year intercepts were employed to isolate within-state effects. States with high YF coverage (>80%) showed a 16% lower age-standardized aortic mortality compared to low-coverage states (IRR 0.84; 95% CI 0.76-0.93; P = 0.001). E-value analysis for this association was 1.67, indicating robustness against moderate unmeasured confounding. For BCG, associations followed a biologically plausible lag structure, peaking at 15 years post-vaccination (IRR 0.91 per 10 pp. increase; 95% CI 0.85-0.98; P = 0.009). Negative control analysis using Diphtheria-Tetanus-Pertussis (DTP) vaccine, which lacks trained immunity effects, showed no association with aortic mortality (IRR 1.02; P = 0.578), arguing against residual confounding from healthcare access. Causal mediation analysis suggested that 65% of the YF vaccine's association operated through pathways independent of infectious disease reduction. CONCLUSION: Population-level vaccination with YF and BCG is associated with lower aortic mortality in this ecological analysis. These hypothesis-generating findings, supported by negative control validation and temporal consistency across three decades, are compatible with a trained immunity pathway but require confirmation in prospective individual-level studies before causal conclusions can be drawn.
Minja NW, Pulle J, Xu X
… +14 more, Rwebembera J, Atala J, Oyella LM, Kamarembo J, Odong F, Nakagaayi D, de Loizaga S, Danforth K, Longenecker CT, Sable C, Beaton AZ, Okello E, Su Y, Watkins DA
Int J Cardiol
· 2026 Jun · PMID 42320685
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BACKGROUND: Rheumatic heart disease (RHD) interventions are currently being rolled out in Northern Uganda. We recently evaluated a programme to decentralise secondary antibiotic prophylaxis (SAP) from regional hospitals...BACKGROUND: Rheumatic heart disease (RHD) interventions are currently being rolled out in Northern Uganda. We recently evaluated a programme to decentralise secondary antibiotic prophylaxis (SAP) from regional hospitals to primary clinics in Lira and Gulu districts, finding equivalent adherence and high acceptability. The present study evaluated the cost implications of the programme. METHODS: We prospectively assessed costs from the purchaser, patient, and societal perspectives, comparing unit and total costs before and after programme implementation. We used a mixed costing approach, including ingredients-based and step-down costing for direct and indirect costs (respectively) to the purchaser. We assessed patient costs through exit surveys. Cost data were analysed using descriptive statistics and t-tests for changes after implementation. A sensitivity analyses was done around indirect costs. RESULTS: The programme reduced purchaser costs for clinical services (overheads, personnel and medications) by over 50% in both districts. Likewise, it significantly reduced patient costs, by lowering transport costs and productivity losses. To enable this, substantial investments were needed for implementation strategies ("programme costs") to support SAP delivery, especially for equipment and training. Our findings were robust in the sensitivity analysis. CONCLUSION: Compared to current practice, an RHD decentralisation programme reduced the unit cost of SAP to the purchaser, though this was attenuated by higher programme costs. The programme provided financial benefit to low-income households and reduced the volume of RHD care at hospitals. Future projects could seek to reduce programme costs, by streamlining training activities. Our findings can inform the design of RHD programmes in the region.