B-type natriuretic peptide levels predict long-term mortality in a large cohort of adults with congenital heart disease.

BACKGROUND AND AIMS: Many adult patients with congenital heart disease (ACHD) are still afflicted by premature death. Previous reports suggested natriuretic peptides may identify ACHD patients with adverse outcome. The study investigated prognostic power of B-type natriuretic peptide (BNP) across the spectrum of ACHD in a large contemporary cohort. METHODS: The cohort included 3392 consecutive ACHD patients under long-term follow-up at a tertiary ACHD centre between 2006 and 2019. The primary study endpoint was all-cause mortality. RESULTS: A total of 11 974 BNP measurements were analysed. The median BNP at baseline was 47 (24-107) ng/L. During a median follow-up of 8.6 years (29 115 patient-years), 615 (18.1%) patients died. On univariable and multivariable analysis, baseline BNP [hazard ratio (HR) 1.16, 95% confidence interval (CI) 1.15-1.18 and HR 1.13, 95% CI 1.08-1.18, respectively] and temporal changes in BNP levels (HR 1.22, 95% CI 1.19-1.26 and HR 1.19, 95% CI 1.12-1.26, respectively) were predictive of mortality (P < .001 for both) independently of congenital heart disease diagnosis, complexity, anatomic/haemodynamic features, and/or systolic systemic ventricular function. Patients within the highest quartile of baseline BNP (>107 ng/L) and those within the highest quartile of temporal BNP change (>35 ng/L) had significantly increased risk of death (HR 5.8, 95% CI 4.91-6.79, P < .001, and HR 3.6, 95% CI 2.93-4.40, P < .001, respectively). CONCLUSIONS: Baseline BNP and temporal BNP changes are both significantly associated with all-cause mortality in ACHD independent of congenital heart disease diagnosis, complexity, anatomic/haemodynamic features, and/or systolic systemic ventricular function. B-type natriuretic peptide levels represent an easy to obtain and inexpensive marker conveying prognostic information and should be used for the routine surveillance of patients with ACHD.

Prognostic significance of subpulmonary left ventricular size and function in patients with a systemic right ventricle.

AIMS: To assess the additional prognostic significance of echocardiographic parameters of subpulmonary left ventricular (LV) size and function in patients with a systemic right ventricle (SRV). METHODS AND RESULTS: All adults with an SRV who underwent transthoracic echocardiography in 2010-18 at a large tertiary centre were identified. Biventricular size and function were assessed at the most recent examination. The study endpoint was all-cause mortality or heart/heart-lung transplantation. We included 180 patients, with 100 (55.6%) males, with a mean age of 42.4 ± 12.3 years, of whom 103 (57.2%) had undergone Mustard/Senning operations and 77 (42.8%) had congenitally corrected transposition of great arteries. Over 4.9 (3.8-5.7) years, 28 (15.6%) patients died and 4 (2.2%) underwent heart or heart-lung transplantation. Univariable predictors of the study endpoint included age, New York Heart Association functional Class III or IV, history of atrial arrhythmias, presence of a pacemaker or cardioverter defibrillator, high B-type natriuretic peptide, and echocardiographic markers of SRV and subpulmonary LV size and function. On multivariable Cox analysis of echocardiographic variables, indexed LV end-systolic diameter [ESDi; hazard ratio (HR) 2.77 (95% confidence interval, CI) 1.35-5.68, P = 0.01], LV fractional area change [FAC; HR 0.7 (95% CI 0.57-0.85), P = 0.002), SRV basal diameter [HR 1.66 (95% CI 1.21-2.29), P = 0.005], and SRV FAC [HR 0.65 (95% CI 0.49-0.87), P = 0.008] remained predictive of mortality or transplantation. On receiver-operating characteristic analysis, subpulmonary LV parameters performed better than SRV markers in predicting adverse events. CONCLUSION: SRV basal diameter, SRV FAC, LV ESDi, and LV FAC are significantly and independently associated with mortality and transplantation in adults with an SRV. Accurate echocardiographic assessment of both SRV and subpulmonary LV is, therefore, essential to inform risk stratification and management.

Differential biventricular adaption to pulmonary vascular disease in patients with idiopathic/heritable and congenital heart disease: a prospective cardiac magnetic resonance and invasive study.

AIMS: Despite shared pathophysiological mechanisms, patients with idiopathic/heritable pulmonary arterial hypertension (IPAH/HPAH) have a poorer prognosis than those with PAH after congenital heart defect repair. Ventricular adaption remains unclear and could provide a basis for explaining differences in clinical outcomes. The aim of this prospective study was to assess clinical status, haemodynamic profile, and biventricular adaptation to PAH in children with various forms of PAH. METHODS AND RESULTS: Consecutive patients with IPAH/HPAH or post-operative PAH were prospectively recruited (n = 64). All patients underwent a comprehensive, protocolized assessment including functional assessment, measurement of brain natriuretic peptide (BNP) levels, invasive measurements, and a cardiac magnetic resonance (CMR) assessment. A cohort of age- and sex-matched healthy subjects served as controls. Patients with post-operative PAH had a better functional class (61.5 vs. 26.3% in Class I/II, P = 0.02) and a longer 6-min walk distance (320 ± 193 vs. 239 ± 156 m, P = 0.008) than IPAH/HPAH. While haemodynamic parameters were not significantly different between IPAH/HPAH and post-operative patients, post-operative patients with PAH presented with higher left ventricular volumes and better right ventricular function compared with patients with IPAH/HPAH (P < 0.05). On correlation analyses, left ventricular volumetric parameters were highly correlated with BNP and 6-min walk test distance in this population. CONCLUSION: Despite comparable haemodynamic profiles, patients with post-operative PAH had less functional limitation than their IPAH/HPAH counterparts. This is potentially related to the differential biventricular adaptation pattern evident on CMR with better myocardial contractility and higher left ventricular volumes in post-operative patients with PAH, highlighting the importance of ventriculo-ventricular interaction in the setting of PAH.

Double outlet ventricles: review of anatomic and imaging characteristics.

Hearts with double outlet ventricles and concordant atrioventricular connections account for about 1%-3% of all cases of congenital heart disease. We review hearts with two ventricles and concordant atrioventricular connections with double outlet right ventricle (DORV), double outlet left ventricle (DOLV) and double outlet both ventricles (DOBV) from the morphological and clinical imaging perspectives. These hearts are a heterogeneous group of congenital cardiac malformations with a wide range of pathophysiologies that require an individualised surgical approach based on a precise understanding of the complex cardiovascular anatomy. Owing to their differing temporal, spatial and contrast resolutions, we propose that multimodality imaging provides optimal characterisation of various intracardiac morphological features of double outlet hearts. This approach aids clinical diagnosis for optimising treatment options across these malformations.

Association between Genotype, Presentation, and Outcome in Childhood Idiopathic and Hereditary Pulmonary Arterial Hypertension.

BACKGROUND: Paediatric-onset idiopathic/hereditary pulmonary arterial hypertension (IPAH/HPAH) is partially linked to genetic factors that may also affect treatment response and outcome. The relation between clinical characteristics and pathogenicity of gene variants in childhood IPAH/HPAH is still not well understood. METHODS: We retrospectively analyzed IPAH/HPAH paediatric patients aged between 3 months and 18 years under follow-up at a large tertiary referral center. Whole-exome sequencing focused on PAH high-risk genes was performed in all patients. Pathogenicity grading of gene variant sites was assessed using ClinVar and population frequencies. The association between gene variants and death was studied using Cox proportional multivariate models. RESULTS: Overall, 129 patients (54.3% females; 91.5% on PAH therapy) with a median age at diagnosis of 6.8 (IQR 3.4-10.7) years were included. A relevant PAH gene variant was detected in 95 patients (73.6%). The most common variants were in the BMPR2 (n = 43, 3%) gene. Over a median follow-up period of 27.6 months, 26 children died. The presence of a likely pathogenic genetic variant was significantly associated with survival (HR: 3.56, p = 0.005) on multivariable Cox analysis. The number of PAH-specific drugs at presentation was associated with better survival in the cohort with pathogenic variants (p = 0.02). CONCLUSIONS: Pathogenic/likely pathogenic genetic variants are prevalent in children with PAH and are related to a worse prognosis irrespective of other recognized risk factors in this population. Combination PAH therapy was associated with superior prognosis in children with pathogenic variants or BMPR2 variants. Therefore, proactive medical therapy should be employed in this population.

Right Heart Catheterization in Pediatric Pulmonary Arterial Hypertension: Insights and Outcome from a Large Tertiary Center.

Aim: To define the clinical characteristics, hemodynamics, and adverse events for pediatric patients with pulmonary arterial hypertension (PAH) undergoing right heart catheterization (RHC). Methods: The large referral single center data of 591 diagnostic RHC procedures performed between 2005 and 2020 on pediatric PAH patients was retrospectively collected and analyzed. Results: A total of 591 RHC procedures performed on 469 patients with congenital heart disease (CHD)-PAH (median age 8.8 years, 7.9% New York Heart Association (NYHA) class > II, 1.5% with syncope) and 122 patients with idiopathic PAH (median age of 9.0 years, 27.0% NYHA class > II, 27.0% with syncope) were included. Of those, 373 (63.1%) procedures were performed under general anesthesia. Eighteen patients (18/591, 3.0%) suffered adverse events (mainly pulmonary hypertensive crisis, PHC, n = 17) during the RHC procedure, including 14 idiopathic pulmonary arterial hypertension (IPAH) patients and 4 CHD-PAH patients, and one IPAH patient died in hospital 63 hours after RHC. The risk of developing PHC was significantly increased in patients with IPAH (OR = 14.02, 95%CI: 4.49−43.85, p < 0.001), atrial blood gas pH < 7.35 (OR = 12.504, 95%CI: 3.545−44.102, p < 0.001) and RAP > 14 mmHg (OR = 10.636, 95%CI: 3.668−30.847, p < 0.001). Conclusions: RHC is generally a low-risk procedure in pediatric patients with PAH. However, PHC occur in approximately 3% of patients. Therefore, RHC should be performed in a large, experienced referral pediatric cardiology center, especially in pediatric patients with IPAH requiring general anesthesia.

Better Outcomes in Pulmonary Arterial Hypertension After Repair of Congenital Heart Disease, Compared With Idiopathic Pulmonary Arterial Hypertension.

BACKGROUND: Pulmonary vascular changes in postoperative pulmonary artery hypertension (PAH) are similar to those seen in idiopathic PAH. Data are sparse on direct comparative midterm outcomes for these 2 high-risk populations. METHODS: Patients with idiopathic or postoperative PAH referred to a large tertiary hospital between June 2005 and July 2019 were retrospectively evaluated. RESULTS: A total of 364 consecutive patients were studied, including 201 postoperative PAH patients and 163 patients with idiopathic PAH, with a median age of 18.7 (interquartile range 10.0, 31.5) and 7.3 (IQR: 2.9, 18.3) years, respectively. PAH-specific drugs were used in 77.7% of patients; 31.4% received combination therapy. Patients with idiopathic PAH had a shorter 6-mintue walk distance, lower percutaneous oxygen saturation, and higher B-type natriuretic peptide levels than those with postoperative PAH at diagnosis (all P < 0.001), During a median follow-up time of 3.4 (interquartile range: 2.1, 5.8) years, 56 patients (15.4%) died, and one underwent bilateral lung transplantation. Patients with postoperative PAH had better survival than those with idiopathic PAH, according to age (hazard ratio [HR] 0.128, 95% confidence interval [CI]: 0.07-0.22, P < 0.0001); Kaplan-Meier survival estimates at 5 years for idiopathic and postoperative PAH patients were 74.3% and 92.6%, respectively. Patients in New York Heart Association functional class III-IV had an over 4-fold increased risk of death (HR 4.85, 95% CI: 2.61-9.00, P < 0.0001). Patients < 18 years of age at idiopathic PAH diagnosis had a worse survival compared to adult patients (HR 6.90, 95% CI: 4.19-15.56, P = 0.040). CONCLUSIONS: Postoperative-PAH patients had better midterm survival compared to patients with idiopathic PAH. Mortality was significant in both PAH groups, reinforcing the need for early diagnosis and optimal individualized management to improve outcomes.

CONTEXTE: Les changements vasculaires pulmonaires associés à l'hypertension artérielle pulmonaire (HAP) postopératoire sont semblables à ceux observés dans l'HAP idiopathique. On dispose de peu de données comparatives directes sur les résultats à moyen terme dans ces deux populations à risque élevé. MÉTHODOLOGIE: Les patients présentant une HAP idiopathique ou postopératoire qui avaient été dirigés vers un important centre hospitalier de soins tertiaires entre juin 2005 et juillet 2019 ont fait l'objet d'une évaluation rétrospective. RÉSULTATS: Au total, 364 patients consécutifs ont été étudiés, dont 201 cas d'HAP postopératoire et 163 cas d'HAP idiopathique, dont l'âge médian était de 18,7 (intervalle interquartile : de 10,0 à 31,5) et de 7,3 (intervalle interquartile : de 2,9 à 18,3) ans, respectivement. Des médicaments traitant précisément l'HAP avaient été utilisés chez 77,7 % des patients; 31,4 % des patients avaient reçu un traitement en association. Chez les patients présentant une HAP idiopathique, la distance parcourue au test de marche de six minutes était inférieure, la saturation percutanée en oxygène était inférieure et les taux de peptide natriurétique de type B étaient supérieurs aux valeurs affichées par les patients présentant une HAP postopératoire au diagnostic (toutes les valeurs p < 0,001). Pendant une période de suivi d'une durée médiane de 3,4 (intervalle interquartile : de 2,1 à 5,8) ans, 56 patients (15,4 %) étaient décédés, et un patient avait subi une transplantation pulmonaire bilatérale. La survie des patients présentant une HAP postopératoire était supérieure à celle des patients avec une HAP idiopathique, en fonction de l'âge (rapport des risques instantanés [RRI] 0,128, intervalle de confiance à 95 % [IC] : de 0,07 à 0,22, p < 0,0001); la survie à cinq ans des patients atteints d'HAP idiopathique et postopératoire, estimée selon la méthode de Kaplan-Meier, était de 74,3 % et de 92,6 %, respectivement. Chez les patients appartenant aux classes fonctionnelles III et IV de la New York Heart Association, le facteur multiplicatif du risque de décès était plus de quatre fois supérieur (RRI 4,85, IC à 95 % : de 2,61 à 9,00, p < 0,0001). Les patients âgés de moins de 18 ans au moment du diagnostic d'HAP idiopathique avaient un taux de survie inférieur à celui des patients adultes (RRI 6,90, IC à 95 % : de 4,19 à 15,56, p = 0,040). CONCLUSIONS: La survie à moyen terme des patients atteints d'une HAP postopératoire était supérieure à celle des patients dont l'HAP était idiopathique. La mortalité était importante dans les deux groupes d'HAP, ce qui met en lumière la nécessité d'un diagnostic précoce et d'une prise en charge individualisée optimale afin d'améliorer les résultats.

Biomimetic Mesoporous Silica Nanoparticles for Enhanced Blood Circulation and Cancer Therapy.

The biomimetic cell membrane camouflaged approach provides numerous opportunities in designing therapeutic platforms for various biomedical applications. It is necessary to understand the engineering of physicochemical properties on materials' surfaces for target biological functions to develop the next-generation anticancer nanomedicines. Herein, we envelope mesoporous silica nanoparticles (MSNs) with red blood cell (RBC) membrane ghosts to obtain MSN@RBC, which possesses significantly stronger physiological stability and longer circulation time than bare MSNs. The surface functionalization of the core material is a critical design parameter for RBC membrane coating efficiency. Therefore, various surface functionalization (-COOH, -SH, -NH2) modifications were performed on MSNs. Compared with other groups, MSN-COOH possessed a better RBC membrane coating efficiency. Then, MSN-COOH of different particle sizes were coated by RBC-derived vesicle membranes. The results indicated that smaller types were able to last longer in blood circulation and accumulate more in target sites than the larger ones. Overall, MSN-ICG@RBC with surface functionalization of -COOH and optimized particle size of 60 nm led to efficient imaging-guided photothermal cancer treatment and could be potentially appealing to actual clinical applications in the future.

Peripartum outcomes in a large population of women with pulmonary arterial hypertension associated with congenital heart disease.

AIMS: Pulmonary arterial hypertension is a severe complication in patients with congenital heart disease and poses a significant risk to women wishing to become pregnant. This study describes the clinical presentation, maternal outcomes and risk factors for the peripartum period in women with pulmonary arterial hypertension related to congenital heart disease (PAH-CHD). METHODS: All pregnant women with PAH-CHD who were admitted for delivery in a tertiary center between February 2011-September 2016 were included. Logistic regression analysis was used to identify predictors of the combined endpoint of maternal death, severe heart failure requiring treatment, or pulmonary hypertensive crisis. RESULTS: Ninety-three women (94 pregnancies) were included. Average age was 27.5 ± 4.4 years. Thirty (31.9%) patients had Eisenmenger syndrome, 51 (54.3%) had pulmonary arterial hypertension associated with systemic-to-pulmonary shunts, and 13 (13.8%) had pulmonary arterial hypertension with corrected congenital heart disease. Twenty-three (24.5%) women required admission for delivery within two days from presentation. Elective Cesarean section was performed in 95.7% of women, with intravertebral anesthesia in 93.6%. Fifty-one (54.2%) patients received pulmonary arterial hypertension therapies during pregnancy. Six (6.4%) women died, 33 (35.1%) developed heart failure and 10 (10.6%) had a pulmonary hypertensive crisis. Patients who met the combined endpoint (n = 34, 36.2%) were more likely to have Eisenmenger syndrome or repaired defects (p < 0.001). Other risk factors in the multivariate model included lower arterial blood oxygen saturation, higher brain natriuretic peptide, and pericardial effusion on echocardiography. CONCLUSION: Maternal mortality and morbidity remain high in PAH-CHD patients, who should be counseled on the risks of pregnancy and managed in a tertiary multidisciplinary environment to improve prognosis.

Diet, lifestyle and cognitive function in old Chinese adults.

BACKGROUND: The relationship between diet, lifestyle and cognition of old adults has been indicated in several population-based studies. However, the conclusions derived from these studies are inconsistent. METHODS: A cross-sectional study was carried out in 894 old Chinese adults aged 50 and above. Cognitive function of the participants was measured by using Montreal Cognitive Assessment (MoCA) test. Demographic characteristics and lifestyle was collected with a questionnaire. A semi-quantified FFQ method was used for dietary intake survey. RESULTS: Comparing with normal subjects, mild cognition impairment (MCI) patients were characterized as old age and lower education (P<0.01). The nuts and cooking oil intake of MCI patients was less than the normal subjects (P<0.05). Fruit and vegetable intake will benefit orientation, name and attention ability in the elderly (P<0.05). Fruit and vegetable juice drinking will benefit abstraction ability (P<0.01).Subjects with regular reading and housekeeping habit had better cognition (P<0.01). CONCLUSIONS: Nuts, vegetables and fruit-rich diet might decrease the risk of cognition impairment. Reading and housekeeping help to maintain healthy cognition in the elderly.