Federico Gutiérrez-Larraya

BACKGROUND: Patients with congenital or acquired right ventricular outflow tract dysfunction frequently require pulmonary valve replacement and are exposed to repeated surgical interventions due to prosthetic valve degeneration. The PULSTA self-expanding transcatheter pulmonary valve was designed to address a broad spectrum of native and surgically repaired right ventricular outflow tract anatomies. This study reports the midterm safety, hemodynamic performance, and durability outcomes of the prospective, multinational PULSTA CE approval trial (PULSTA Carpentier Edwards). METHODS: This premarket, multicenter, nonrandomized study enrolled 58 patients across 11 centers in 6 countries. Successful PULSTA implantation was achieved in 57 patients (98.3%), including 4 valve-in-valve procedures. Patients were followed for a median duration of 4.1 years. Primary end points included procedural or device-related serious adverse events, hemodynamic improvement, and sustained valve function. RESULTS: At 6 months, cardiac magnetic resonance imaging demonstrated significant reverse right ventricular remodeling, with marked reductions in right ventricular end-diastolic volume index, end-systolic volume index, and pulmonary regurgitation fraction (all P <0.001). Valve performance remained stable throughout follow-up, with 93.8% of patients exhibiting mild or less pulmonary regurgitation at 4.1 years. Freedom from reintervention was 98.2% at 5 years. One patient required a PULSTA-in-PULSTA implantation due to paravalvular leakage, and one case of infective endocarditis was successfully managed with antibiotic therapy. No stent fractures or structural valve deterioration were observed. CONCLUSIONS: The PULSTA transcatheter pulmonary valve demonstrated high procedural success, durable valve function, and sustained hemodynamic benefits. Its adaptability to diverse right ventricular outflow tract anatomies and favorable safety profile supports its role as an effective therapeutic option for patients with right ventricular outflow tract dysfunction. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03983512.

Background/Objectives: Acute rejection remains a major challenge in pediatric heart transplantation (HT), with limited tools for early diagnosis. In adult HT recipients, microcirculatory dysfunction, as measured by the index of microcirculatory resistance (IMR), has been identified as a potential biomarker of rejection. However, its role in pediatric populations is largely unexplored. This pilot study aimed to evaluate the association between coronary microcirculatory dysfunction and acute rejection in pediatric heart transplant recipients, as well as its relationship with echocardiographic alterations. Methods: This prospective, single-center study included 10 pediatric HT recipients who underwent routine coronary angiography and endomyocardial biopsy. The IMR, coronary flow reserve (CFR), and fractional flow reserve (FFR) were assessed. Acute rejection was classified as either acute cellular rejection (ACR) or antibody-mediated rejection (AMR) based on ISHLT criteria. Echocardiographic parameters included left ventricular ejection fraction (LVEF), global longitudinal strain (GLS), right ventricular (RV) dysfunction, and diastolic function. Patients were followed for a median of 9.7 months [IQR: 7.0–11.7]. Results: Patients with a history of acute rejection (40%, n = 4) were exclusively found in the IMR ≥ 15 group (66.7%), while no cases were observed in the IMR < 15 group (0%; p = 0.04). During follow-up, only one patient experienced acute rejection, occurring in the IMR ≥ 15 group, although the difference between groups was not statistically significant (p = 0.39). Both LVEF and GLS were worse in patients with IMR ≥ 15 compared to IMR < 15 (62.5% vs. 76.3% and −17.3% vs. −18.8%, respectively), although these differences did not reach statistical significance. No complications were reported during coronary physiology assessment. Conclusions: Microcirculatory dysfunction, as measured by IMR, was significantly associated with a history of acute cellular rejection in pediatric heart transplant recipients. While its predictive value for acute rejection during follow-up remains unclear due to the small sample size, this pilot study highlights the safety and feasibility of coronary physiology assessment in this population. Larger studies are needed to validate these findings and establish pediatric-specific diagnostic thresholds.

Advanced heart failure and pulmonary hypertension significantly compromise patients' quality of life. This has led to the development of technologies such as the CardioMEMS device for their management. Although its use is widely approved for adults with advanced heart failure [1], its application in pediatrics [2], especially outside conventional heart failure scenarios [3,4], is innovative and considered compassionate due to the lack of approval by regulatory entities such as the FDA and CE marking for this age group. On the other hand, cardiac catheterizations in pediatric patients, especially diagnostic procedures to assess pulmonary pressures, are not without risks [5].

Cardiotoxicity due to anthracyclines (CDA) affects cancer patients, but we cannot predict who may suffer from this complication. CDA is a complex trait with a polygenic component that is mainly unidentified. We propose that levels of intermediate molecular phenotypes (IMPs) in the myocardium associated with histopathological damage could explain CDA susceptibility, so variants of genes encoding these IMPs could identify patients susceptible to this complication. Thus, a genetically heterogeneous cohort of mice (n = 165) generated by backcrossing were treated with doxorubicin and docetaxel. We quantified heart fibrosis using an Ariol slide scanner and intramyocardial levels of IMPs using multiplex bead arrays and QPCR. We identified quantitative trait loci linked to IMPs (ipQTLs) and cdaQTLs via linkage analysis. In three cancer patient cohorts, CDA was quantified using echocardiography or Cardiac Magnetic Resonance. CDA behaves as a complex trait in the mouse cohort. IMP levels in the myocardium were associated with CDA. ipQTLs integrated into genetic models with cdaQTLs account for more CDA phenotypic variation than that explained by cda-QTLs alone. Allelic forms of genes encoding IMPs associated with CDA in mice, including AKT1, MAPK14, MAPK8, STAT3, CAS3, and TP53, are genetic determinants of CDA in patients. Two genetic risk scores for pediatric patients (n = 71) and women with breast cancer (n = 420) were generated using machine-learning Least Absolute Shrinkage and Selection Operator (LASSO) regression. Thus, IMPs associated with heart damage identify genetic markers of CDA risk, thereby allowing more personalized patient management.

Revista Española de Cardiología: Interventional Cardiology

En los pacientes con DCPT, la disfunción ventricular es inevitable, y más temprana en VU derechos. La deformación miocárdica por STE y RMC-FT parece promisoria. Objetivo: Analizar la función ventricular mediante STE y RMC-FT en pacientes con DCPT, en comparación con RMC convencional según la morfología del VU y la posible implicación en su diagnóstico temprano. Método: Se recogieron medidas del strain longitudinal y circunferencial por STE y RMC-FT, volúmenes ventriculares y FE por RMC en 64 pacientes con DCPT. Resultados: La morfología ventricular no se relacionó con disfunción por RMC. Los VU derechos tuvieron valores por STE y RMC-FT disminuidos respecto de los VU izquierdos, con FE similares. Existe correlación entre STE y RMC-FT, no equivalentes, con buena factibilidad y reproducibilidad. Conclusiones: La RMC-FT y el STE son técnicas útiles en el diagnóstico temprano y la vigilancia de la función ventricular en VU derechos con FE preservada.

Objectives: The aim of the study was first to quantify the diagnostic accuracy of predictive anatomical factors of aortic coarctation (CoA) and second to design a postnatal CoA probability algorithm according to gestational age (GA) in prenatal period. Methods: Global and according to GA diagnostic performance of cardiac anatomical variables using the ROC curve were evaluated in a retrospective cohort of fetuses with suspicion of CoA (2004–2020). A serial testing strategy to predict postnatal CoA by fetal echocardiography was designed. Results: 114 fetuses were included. Isthmus-to-ductal (I/D) ratio provided the best discrimination between healthy fetuses and those with CoA (AUC 0.91, 95% CI: 0.86–0.96, I/D < 0.74 sensitivity 96.3%, I/D < 0.6, specificity 92.5%) with good classification capacity in both the second and third trimesters of gestation. Isthmus z-score and pulmonary/aortic valve ratio increased accuracy in fetuses >28 and tricuspid/mitral valve ratio (TV/MV) in fetuses ≤28 weeks. Study of I/D plus TV/MV ratio in fetuses ≤28 and I/D ratio plus isthmus z-scores in fetuses >28 weeks allowed to correctly classify 91.8% of fetuses as high or low probability of postnatal CoA. Conclusions: Diagnostic discrimination of anatomic predictive factors for CoA varies according to GA. Specific algorithms according to GA increase accuracy in CoA’s prenatal prediction.