ABSTRACT Pregnancy poses substantial risks for women with Pulmonary Arterial Hypertension (PAH). This study aimed to evaluate maternal and neonatal outcomes in a contemporary PAH cohort under modern management, specifically investigating whether vasoreactive status warrants distinct clinical recommendations. We conducted a retrospective, longitudinal cohort study of PAH pregnancies managed at our institution between February 2010 and December 2023, comparing clinical characteristics, maternal complications, long‐term outcomes, and neonatal parameters between vasoreactive and non‐vasoreactive patients. Among 29 patients, 8 underwent pregnancy termination, and 21 proceeded with the pregnancy; 7 (33.3%) of whom were vasoreactive. Non‐vasoreactive patients experienced significantly higher rates of major complications (35.7% vs. 0%, p = 0.039) and minor complications (92.9% vs. 0%, p < 0.001). Complications in the non‐vasoreactive subgroup included prostacyclin initiation (78.6%), inotropic support (35.7%), mechanical circulatory support (14.3%), and one death (7.14%). All neonates born to non‐vasoreactive patients were delivered preterm and showed a trend toward higher complication rates (84.6% vs. 42.9%, p = 0.054). Over a median 5‐year follow‐up, two non‐vasoreactive patients died, whereas none of the vasoreactive patients lost their vasoreactive profile. In conclusion, despite advances in management, pregnancy in PAH remains associated with substantial maternal and neonatal morbidity. Vasoreactive patients, however, exhibit a distinctly favorable prognosis for both mother and offspring, which suggest the need for tailored recommendations for this subgroup.

BACKGROUND:Left atrial macroreentrant tachycardias (LAMRTs) are increasing, particularly following atrial fibrillation ablation. Conventional ablation strategies based on activation mapping are limited by the presence of multiple inducible circuits and high recurrence rates. The potential benefit of a substrate-guided approach targeting reproducible anatomical reentry pathways remains unknown. We hypothesize that a substrate-guided approach, targeting reproducible anatomical pathways sustaining reentry rather than only inducible tachycardias, will improve rhythm control and clinical outcomes compared with conventional ablation strategies. OBJECTIVE:The goal of this trial is to determine whether substrate-guided catheter ablation is superior to activation-guided ablation in reducing atrial arrhythmia recurrence in patients with LAMRT. METHODS:The SLICE-LAMRT trial is an investigator-initiated, prospective, multicenter, randomized (1:1) study conducted at 12 centers in Spain. Patients and clinical event adjudicators are blinded to treatment allocation. Patients with LAMRT and significant left atrial low-voltage substrate are randomized to either a conventional activation-guided ablation strategy, based on high-density mapping and entrainment pacing of clinical and inducible tachycardias, or a substrate-guided approach consisting of a predefined left atrial ablation line set. This study has been registered at ClinicalTrials.gov (NCT05842499). The primary endpoint is atrial tachyarrhythmia recurrence and time to first recurrence after a 3-month blanking period. Secondary endpoints include procedural performance, acute efficacy, major clinical outcomes (including hospitalizations and mortality), and echocardiographic parameters. Safety endpoints include procedure-related adverse events such as death, stroke, cardiac tamponade, vascular complications, and other major complications. CONCLUSION:The SLICE-LAMRT trial will provide the first randomized evidence comparing substrate-guided and activation-guided ablation strategies in LAMRT. By addressing a major unmet clinical need, this study may inform and refine ablation strategies for atypical atrial flutter and support a shift toward substrate-based approaches in complex atrial arrhythmias.

BACKGROUND:Outcomes after heart transplantation remain highly variable, and traditional risk models perform poorly in this heterogeneous population. We sought to identify clinically meaningful recipient subgroups and assess their prognostic implications using latent class analysis (LCA). METHODS:We analyzed all adult recipients of a first isolated heart transplantation in Spain. LCA based on pretransplant characteristics identified recipient phenogroups, whose 5-y all-cause mortality was compared using Cox models and internally validated with bootstrap resampling and Harrell's C-statistics. RESULTS:Among 3683 recipients (74.5% male), 3 phenogroups were identified. Phenogroup 1 (41.3%) included younger patients, more women, dilated cardiomyopathy, and fewer comorbidities. Phenogroup 2 (22.1%) comprised older men with ischemic cardiomyopathy and high comorbidity burden. Phenogroup 3 (36.6%) represented urgent transplants with frequent circulatory support, ventilation, and longer ischemia. Five-year mortality was 24.0%, 28.5%, and 33.0% across groups ( P < 0.001). Compared with phenogroup 1, mortality risk was higher in phenogroup 2 (HR = 1.20; 95% confidence interval, 1.02-1.41) and phenogroup 3 (HR = 1.47; 95% confidence interval, 1.28-1.69). Causes of death differed, graft failure predominating in phenogroup 1 and infection in phenogroups 2 and 3. Internal validation confirmed high model stability (entropy 0.99) and modest discrimination (optimism-adjusted C-statistic 0.55). CONCLUSIONS:LCA identified 3 reproducible clinical phenogroups with distinct prognoses and mechanisms of death. Recognizing these patterns may refine posttransplant surveillance and guide phenotype-based management strategies.

Urinary sodium (UNa) is a powerful predictor of adverse events in acute heart failure (AHF), although its etiopathogenic mechanism remains poorly understood. Previous studies highlight the importance of venous congestion on renal function in AHF. Our objective was to evaluate the relationship between right ventricular (RV) function and UNa, as well as their prognostic interaction in AHF. We prospectively analyzed 101 patients hospitalized for AHF, divided into high or low natriuresis groups based on the median natriuretic response to a furosemide stress test. We performed a comprehensive echocardiographic assessment of RV size and function. The clinical outcome was a 6-month composite of all-cause mortality, heart failure rehospitalization, or heart transplantation. The median age was 65 (56–80) years, with 63.4

Background Cytomegalovirus (CMV) infection is associated with worse outcomes after heart transplant (HT). CMV mismatch (donor positive, recipient negative serology, D+/R-) increases the risk of infection. Guidelines recommend 3 to 6 months of antiviral prophylaxis in these patients. An increase in primary CMV infections at our center prompted us to analyses this population in search of improvement. Methods From 185 adult HT receptors in 10 years, we selected those with CMV D+/R-. Patients were followed until October 2023. We evaluated the patterns of transmission of CMV in accordance with current recommendations. Results We assessed 35 HT recipients with CMV mismatch (median age of 48.8 ± 13.8 years, 71% men). Median follow-up was 5.5 years [1.9-7.4]. Median duration of CMV prophylaxis was 3.7 (±2.1) months post-HT. CMV infection occurred in 74% of patients (96% within the first 6 months after ending prophylaxis) and CMV disease in 26%. Half of them required hospital admission. One third had concomitant infections by other microorganisms. There were no significant differences in the duration of prophylaxis between patients with and without CMV infection. Survival on follow-up was 77%. 2 patients died during CMV infection due to other infection. Conclusions CMV infection rate in D+/R- HT receptors remains high even after the prophylactic period recommended by current guidelines. A better knowledge of CMV-transmitted infection, coupled with the pursuit of a suitable equilibrium between the prevention of infection and rejection, have the potential to enhance the outcomes of this high-risk population through tailored protocols.

INTRODUCTION AND OBJECTIVES:Worsening renal function (WRF) is a frequent complication in acute heart failure (AHF) with a controversial prognostic value. We aimed to study the usefulness of natriuresis to evaluate WRF. METHODS:We conducted an observational, prospective, multicenter study of patients with AHF who underwent a furosemide stress test. The patients were classified according to whether WRF was present or absent and according to the median natriuretic response. The main endpoint was the combination of mortality, rehospitalization due to HF, and heart transplant at 6 months of follow-up. RESULTS:One hundred and fifty-six patients were enrolled, and WRF occurred in 60 (38.5%). The patients were divided into 4 groups: a) 47 (30.1%) no WRF/low UNa (UNa ≤ 109 mEq/L); b) 49 (31.4%) no WRF/high UNa (UNa >109 mEq/L); c) 31 (19.9%) WRF/low UNa and d) 29 (18.6%) WRF/high UNa. The parameters of the WRF/low UNa group showed higher clinical severity and worse diuretic and decongestive response. The development of WRF was associated with a higher risk of the combined event (HR, 1.88; 95%CI, 1.01-3.50; P=.046). When stratified by natriuretic response, WRF was associated with an increased risk of adverse events in patients with low natriuresis (HR, 2.28; 95%CI, 1.15-4.53; P=.019), but not in those with high natriuresis (HR, 1.18; 95%CI, 0.26-5.29; P=.826). CONCLUSIONS:Natriuresis could be a useful biomarker for interpreting and prognosticating WRF in AHF. WRF is associated with a higher risk of adverse events only in the context of low natriuresis.

Renal transplantation improves the survival and quality of life of patients with end-stage renal disease. Cardiovascular disease is the leading cause of morbidity and mortality in renal transplant recipients. The bidirectional relationship between renal and heart disease creates a unique clinical scenario that demands a comprehensive and personalized approach. This expert consensus, drafted by the Spanish Society of Transplantation, the Spanish Society of Cardiology, and the Spanish Society of Nephrology, aims to assess current practices and propose strategies for the management of heart disease in renal transplant recipients. A panel of Spanish nephrologists and cardiologists with expertise in renal and heart transplantation reviewed the scientific evidence concerning the current management of heart disease in renal transplant recipients. Subsequently, consensus statements were created through a 2-round Delphi methodology, resulting in 30 statements covering key topics such as the identification of renal transplant candidates, the management of heart disease in renal transplant recipients, and eligibility for combined heart-kidney transplantation in patients with both end-stage renal disease and cardiac disease. These consensus statements provide expert guidance for the management of heart disease in renal transplant recipients, an area where published clinical evidence remains limited.

Introducción y objetivos El fracaso primario del injerto (FPI) grave es la principal causa de muerte tras el trasplante cardiaco (TxC). Este estudio analizó la evolución temporal y la mortalidad del FPI grave, identificó factores de riesgo y desarrolló un modelo predictivo en una cohorte contemporánea. Métodos Se analizaron retrospectivamente 2.029 TxC realizados entre 2010-2020 en 14 centros españoles. Se compararon pacientes con y sin FPI grave. Se realizó un análisis de regresión logística para identificar predictores de FPI grave y generar una puntuación de riesgo. Se evaluó el comportamiento del modelo (calibración, discriminación). Resultados La incidencia de FPI grave fue del 10%, y aumentó en los últimos 5 años (8 vs 11%). La mortalidad a 30 días y 1 año disminuyó significativamente (59,1 vs 38,8% y 69,7 vs 58,8%, respectivamente). Los predictores de FPI grave incluyeron oxigenador extracorpóreo de membrana (ECMO) (OR=2,79), dispositivos de asistencia ventricular (DAV) pretrasplante (OR=2,11), relación de peso donante/receptor (D/R) <0,8 (OR=2,11) y cardiopatía congénita (OR=2,11). Se creó una puntuación de riesgo que mostró buena calibración pero una capacidad discriminatoria pobre. Conclusiones Aunque la incidencia de FPI grave aumentó, la mortalidad disminuyó notablemente. Los predictores de FPI grave incluyeron cardiopatía congénita, relación de peso D/R <0,8 y uso de ECMO o DAV pretrasplante. El modelo predictivo mostró buena calibración, pero capacidad discriminatoria moderada.

BACKGROUND:Wide antral circumferential ablation (WACA) is considered the gold standard for pulmonary vein isolation (PVI) in atrial fibrillation (AF) ablation. Single shot devices of increasing diameter, delivering both thermal and pulsed field ablation, are being introduced in clinical practice. However, benefit of ablating larger antral areas on long-term efficacy remains unclear. OBJECTIVE:Our trial aims to determine whether ablation of a larger antral area with a larger single-shot ablation device improves rhythm outcomes compared to traditional single-shot PVI. METHODS:WIDER-PVI is a prospective, multicenter, randomized controlled trial enrolling patients with paroxysmal AF of any duration or persistent AF diagnosed within the two years prior to ablation. Participants are randomized 1:1 to undergo PVI using either a single-shot device with standard (28-mm cryoballoon, control group) or larger (31-mm cryoballoon, experimental group) antral coverage. The dual primary endpoints are [1] freedom from atrial tachyarrhythmia recurrence lasting >30 s at 12 months, and [2] atrial arrhythmia burden, both assessed via wearable or implantable rhythm monitoring systems. Secondary endpoints include acute procedural metrics (procedure duration, left atrial dwell time, fluoroscopy exposure), need for balloon size crossover, recurrence patterns, repeat ablation rates, and cardiovascular events during follow-up. This study has been registered at ClinicalTrials.gov (NCT06698159). CONCLUSION:WIDER-PVI is the first randomized trial to evaluate whether a larger-diameter single-shot device with enhanced antral coverage improves rhythm outcomes compared to standard single-shot PVI. Its findings may guide future ablation strategies, device design, and clinical decision-making in AF treatment.

Background: Noninvasive techniques for diagnosing combined postcapillary pulmonary hypertension (CpcPH) are unavailable. Objective: To assess the diagnostic performance of cardiac magnetic resonance (CMR)-based four-dimensional (4D)-flow analysis in identifying CpcPH. Methods: Prospective observational study of heart failure (HF) patients with suspected pulmonary hypertension (PH) who underwent simultaneous CMR and right heart catheterization. The 4D-flow biomarkers were calculated using an automatic pipeline. A predictive model including 4D-flow biomarkers associated with CpcPH with a p-value < 0.20 was built to determine the diagnostic performance of 4D-flow analysis to identify CpcPH. Results: A total of 46 HF patients (55.4 ± 14 years, 63% male) with confirmed PH (19 [41%] isolated postcapillary PH [IpcPH], 27 [59%] CpcPH) were included. No differences were found in baseline characteristics, echocardiography, or CMR anatomical and functional parameters, except for a higher Doppler-estimated systolic pulmonary pressure and larger pulmonary artery in CpcPH patients. The 4D-flow CMR analysis was performed in 31 patients (67%). The maximal peak velocity (67.1 [62.2–77.5] cm/s—IpcPH vs. 58.2 [45.8–66.0] cm/s—CpcPH; p = 0.021) and maximal helicity (339.9 [290.0–391.8]) cm/s2—IpcPH vs. 226.0 (173.5–343.7) cm/s2—CpcPH; p = 0.026) were significantly lower in patients with CpcPH. A maximal multivariable model including sex, maximal average, and peak velocities, Reynolds number, flow rate, and helicity showed fair diagnostic performance (area under the curve: 0.768 [95%-CI: 0.572–0.963]; sensitivity: 100%; specificity: 55%). Conclusions: In HF patients with PH, 4D-flow-derived maximal peak velocity and maximal helicity were significantly lower in CpcPH patients. A multiparametric model including maximal 4D-flow-derived biomarkers showed good diagnostic performance for identifying CpcPH.

Introducción y objetivos Este informe actualiza los datos sobre el trasplante cardiaco en España, incluyendo los procedimientos realizados en 2024. Se analiza la evolución de las características de receptores y donantes, el procedimiento quirúrgico, la inmunosupresión y la supervivencia en la última década (2015-2024). Métodos Se recopilaron datos del Registro español de trasplante cardiaco, que se actualiza anualmente. Se analizaron 347 trasplantes realizados en 2024 y la evolución de los procedimientos en los años 2015-2023 (n=2.721). Resultados En 2024, se realizó un 6,8% más de trasplantes que en 2023. No hubo cambios significativos en edad y sexo de los receptores, pero aumentó la proporción de trasplantes urgentes (47,0%). Se observó una mayor utilización de dispositivos de asistencia circulatoria, especialmente del oxigenador extracorpóreo de membrana. La edad promedio de los donantes mostró un ligero repunte, pero la tendencia a su reducción sigue siendo significativa. La donación en asistolia representó el 29,1% de los trasplantes en 2024. La supervivencia al primer año ha mejorado, alcanzando el 85,2% en el periodo 2021-2023. Conclusiones El número de trasplantes sigue en aumento, alcanzando cifras cercanas al máximo histórico, impulsado por la expansión de la donación en asistolia. La mejoría en la supervivencia refleja la madurez de los programas de trasplante, la optimización del procedimiento y las mejores condiciones pretrasplante de los receptores.

Aims:Toxic oil syndrome (TOS) was one of the first described forms of drug-induced pulmonary arterial hypertension (PAH). Its long-term clinical evolution remains poorly understood. The objectives of the present study were to provide new clinical, pathological and genetic insights into TOS-associated PAH (TOS-PAH), and to evaluate its long-term outcomes. Methods:Patients diagnosed with TOS-PAH and included in the Spanish Registry of PAH (REHAP) were prospectively analysed. Results:59 new cases were diagnosed between 1997 and 2025 (63% female; median age 47 years), including several in the past two decades. The median interval between TOS exposure and PAH diagnosis was 270.8 months (interquartile range (IQR) 204.9-398.0). Patients diagnosed in earlier periods were younger, with more advanced functional impairment and more severe haemodynamics. In contrast, recent cohorts showed a higher prevalence of cardiovascular and respiratory comorbidities. No significant differences were observed in overall or transplant-free survival across decades (p=0.677). Median transplantation-free survival was 97.2 months (IQR 64.2-199.4). Three patients achieved complete haemodynamic resolution. Genetic testing was negative in all evaluated patients. Pathological findings were comparable with those observed in other PAH forms, with some cases with significant venous remodelling. Conclusions:TOS-PAH remains a distinct clinical entity, with new cases diagnosed decades after toxic exposure. Despite differences in presentation over time, its long-term clinical course appears similar to that of other PAH types.

Introduction and objectives: The multiparametric implantable cardioverter-defibrillator HeartLogic index has proven to be a sensitive and timely predictor of impending heart failure (HF) decompensation. We evaluated the impact of a standardized follow-up protocol implemented by nursing staff and based on remote management of alerts.Methods: The algorithm was activated in HF patients at 19 Spanish centers. Transmitted data were analyzed remotely, and patients were contacted by telephone if alerts were issued. Clinical actions were implemented remotely or through outpatient visits. The primary endpoint consisted of HF hospitalizations or death. Secondary endpoints were HF outpatient visits. We compared the 12-month periods before and after the adoption of the protocol.Results: We analyzed 392 patients (aged 69 ± 10 years, 76% male, 50% ischemic cardiomyopathy) with implantable cardioverter-defibrillators (20%) or cardiac resynchronization therapy defibrillators (80%). The primary endpoint occurred 151 times in 86 (22%) patients during the 12 months before the adoption of the protocol, and 69 times in 45 (11%) patients (P < .001) during the 12 months after its adoption. The mean number of hospitalizations per patient was 0.39 ± 0.89 pre- and 0.18 ± 0.57 postadoption (P < .001). There were 185 outpatient visits for HF in 96 (24%) patients before adoption and 64 in 48 (12%) patients after adoption (P < .001). The mean number of visits per patient was 0.47 ± 1.11 pre- and 0.16 ± 0.51 postadoption (P < .001).Conclusions: A standardized follow-up protocol based on remote management of HeartLogic alerts enabled effective remote management of HF patients. After its adoption, we observed a significant reduction in HF hospitalizations and outpatient visits.

Objective This study aimed to determine the prevalence of non-adherence to preventive interventions, its clinical consequences, and factors associated with non-adherence to secondary prevention measures, with a special emphasis on sex and gender. Methods Prospective observational study of patients hospitalized for acute myocardial infarction (AMI) in whom an evaluation of adherence to medication, Mediterranean diet, physical activity, and cardiac rehabilitation was performed after 6 and 12 months, with systematic assessment of predictors including patient-, disease-, psychological-, social-, and gender-related factors using self-administered questionnaires. Results Of 503 patients included, 101 (20,1%) were females. At one year, 85% of patients did not adhere to at least one of the recommendations with no differences between females and males. However, two factors more frequent in females, caregiver burden (adjusted OR, 1.45; 95%CI, 1.08-1.94) and depressive symptoms (adjusted OR, 1.40; 95%CI, 1.03-1.92) predicted non-adherence to all measures together. Chronic kidney disease (aOR, 3.24; 95%CI, 1.02-10.48) and being female (aOR, 2.21; 95%CI, 1.18-4.13) were associated with non-adherence to the Mediterranean diet; diabetes with organ damage (aOR, 12.06; 95%CI, 1.93-7.69) and older age (aOR, 0.96 per year; 95%CI, 0.93-0.99), among others, with physical activity; and higher body mass index with cardiac rehabilitation participation (aOR, 1.07; 95%CI, 1.002-1.14) and completion (aOR, 1.14; 95%CI, 1.03-1.26) Conclusion Adherence to all secondary prevention measures after AMI remains very low and is associated with several gender-related factors. Multidisciplinary intervention strategies targeting the most vulnerable patient groups, such as females or patients with diabetes, obesity, chronic kidney disease, or depression, are warranted.

BACKGROUND AND METHODS:Heart transplant recipients (HTr) have a higher probability of suffer from severe coronavirus disease-2019 (COVID-19) in comparison to general population, but their risk has changed over the course of the pandemic in relation to various factors. We conducted a prospective study including all HTr at risk of COVID-19 in a tertiary center between February 2020 and October 2022. The aim was to analyze how the prognosis (incidence of pneumonia and mortality) of COVID-19 in HTr has evolved over time, contextualizing variants, vaccination, and other treatments.RESULTS:Of 308 HTr included, 124 got the infection (39.2%). COVID and non-COVID HTr had similar baseline characteristics. COVID-19 patients with pneumonia had a poorer prognosis than those with less severe presentations, with a higher rate of hospitalization (93.3 vs. 14.1%, p < .001) and death (41.0 vs. 1.2%, p < .001). Multivariate analysis identified age ≥60 years (odds ratio [OR] 3.65, 95% confidence interval [CI] 1.16-11.49, p = .027), and chronic kidney disease ≥3a (OR 4.95, 95% CI 1.39-17.54, p = .014) as predictors of pneumonia. Two-dose vaccination (OR 0.20, CI 95% 0.05-0.72, p = .02) and early remdesivir administration (OR 0.17, CI 0.03-0.90, p = .037) were protective factors. Over the course of the pandemic considering three periods in the follow-up (prevaccination February-December 2020, postvaccination January-December 2021, and post early remdesivir indication January-October 2022), we observed a reduction in pneumonia incidence from 62% to 19% (p < .001); and mortality (from 23% to 4%, p < .001).CONCLUSIONS:The prognosis of COVID-19 in HTr has improved over time, likely due to vaccination and early administration of remdesivir.

El trasplante cardiaco (TxC) sigue siendo la mejor opción terapéutica para pacientes con insuficiencia cardiaca (IC) avanzada. Los criterios de distribución pretenden garantizar un acceso equitativo al TxC y priorizar a los pacientes en situaciones clínicas más comprometidas.

Limited research has been conducted on sex disparities in heart transplant (HT). The aim of this review is to analyse the available evidence on the influence of sex and gender-related determinants in the entire HT process, as well as to identify areas for further investigation. Although women make up half of the population affected by heart failure and related mortality, they account for less than a third of HT recipients. Reasons for this inequality include differences in disease course, psychosocial factors, concerns about allosensitisation, and selection or referral bias in female patients. Women are more often listed for HT due to non-ischaemic cardiomyopathy and have a lower burden of cardiovascular risk factors. Although long-term prognosis appears to be similar for both sexes, there are significant disparities in post-HT morbidity and causes of mortality (noting a higher incidence of rejection in women and of malignancy and cardiac allograft vasculopathy in men). Additional research is required to gain a better understanding of the reasons behind gender disparities in eligibility and outcomes following HT. This would enable the fair allocation of resources and enhance patient care.