Risk factors and clinical prediction models for prolonged mechanical ventilation after heart valve surgery.

OBJECTIVES: Prolonged mechanical ventilation (PMV) is a common complication following cardiac surgery linked to unfavorable patient prognosis and increased mortality. This study aimed to search for the factors associated with the occurrence of PMV after valve surgery and to develop a risk prediction model. METHODS: The patient cohort was divided into two groups based on the presence or absence of PMV post-surgery. Comprehensive preoperative and intraoperative clinical data were collected. Univariate and multivariate logistic regression analyses were employed to identify risk factors contributing to the incidence of PMV. Based on the logistic regression results, a clinical nomogram was developed. RESULTS: The study included 550 patients who underwent valve surgery, among whom 62 (11.27%) developed PMV. Multivariate logistic regression analysis revealed that age (odds ratio [OR] = 1.082, 95% confidence interval [CI] = 1.042-1.125; P < 0.000), current smokers (OR = 1.953, 95% CI = 1.007-3.787; P = 0.047), left atrial internal diameter index (OR = 1.04, 95% CI = 1.002-1.081; P = 0.041), red blood cell count (OR = 0.49, 95% CI = 0.275-0.876; P = 0.016), and aortic clamping time (OR = 1.031, 95% CI = 1.005-1.057; P < 0.017) independently influenced the occurrence of PMV. A nomogram was constructed based on these factors. In addition, a receiver operating characteristic (ROC) curve was plotted, with an area under the curve (AUC) of 0.782 and an accuracy of 0.884. CONCLUSION: Age, current smokers, left atrial diameter index, red blood cell count, and aortic clamping time are independent risk factors for PMV in patients undergoing valve surgery. Furthermore, the nomogram based on these factors demonstrates the potential for predicting the risk of PMV in patients following valve surgery.

Can resistance prehabilitation training bring additional benefits in valvular cardiac surgery? protocol for a randomized controlled trial.

INTRODUCTION: Cardiovascular diseases (CVD) are a group of illnesses that include coronary heart disease, cerebrovascular disease, congenital heart disease and deep vein thrombosis. Major surgery is often chosen as the treatment of choice for CVD. The concept of fast-track rehabilitation after surgery appeared in the 1970s. Participation in these exercise-based prehabilitation programmes may decrease postoperative complications and length of hospital stay. The primary aim of the present study is to evaluate whether the implementation of an additional resistance training (RT) prehabilitation protocol within cardiac exercises based prehabilitation can reduce intensive care unit (ICU) length of stay, postoperative complications and hospital length of stay (LOS). METHODS: A protocol of a prospective, parallel, randomised clinical trial includes 96 adult patients diagnosed with valvular pathology and who have been scheduled for surgery. The participants will be randomly assigned to two groups of 48. Control group will be treated with ventilatory and strengthening of respiratory muscles, and aerobic exercise. Experimental group, in addition, will be treated with RT of peripheral muscles. Both hospital stay and ICU stay will be assessed as main variables. Other secondary variables such as exercise capacity, quality of life and respiratory values will also be assessed. Quantitative variables will be analysed with a T-Test or ANOVA, or Mann Witney if the distribution is non-parametric. RESULTS AND CONCLUSION: This will be the first controlled clinical study focused on adding strength exercise as an additional treatment during prehabilitation. The results of this study will focus on helping to improve rehabilitation and prehabilitation protocols, considering that it is essential to maintain pulmonary training, as well as the inclusion of peripheral exercises that help people with heart disease to be in a better physical condition in order to increase their participation and sense of quality of life.

Comparison study of surface-initiated hydrogel coatings with distinct side-chains for improving biocompatibility of polymeric heart valves.

Polymeric heart valves (PHVs) present a promising alternative for treating valvular heart diseases with satisfactory hydrodynamics and durability against structural degeneration. However, the cascaded coagulation, inflammatory responses, and calcification in the dynamic blood environment pose significant challenges to the surface design of current PHVs. In this study, we employed a surface-initiated polymerization method to modify polystyrene-block-isobutylene-block-styrene (SIBS) by creating three hydrogel coatings: poly(2-methacryloyloxy ethyl phosphorylcholine) (pMPC), poly(2-acrylamido-2-methylpropanesulfonic acid) (pAMPS), and poly(2-hydroxyethyl methacrylate) (pHEMA). These hydrogel coatings dramatically promoted SIBS's hydrophilicity and blood compatibility at the initial state. Notably, the pMPC and pAMPS coatings maintained a considerable platelet resistance performance after 12 h of sonication and 10 000 cycles of stretching and bending. However, the sonication process induced visible damage to the pHEMA coating and attenuated the anti-coagulation property. Furthermore, the in vivo subcutaneous implantation studies demonstrated that the amphiphilic pMPC coating showed superior anti-inflammatory and anti-calcification properties. Considering the remarkable stability and optimal biocompatibility, the amphiphilic pMPC coating constructed by surface-initiated polymerization holds promising potential for modifying PHVs.

Acute Heart Valve Emergencies.

Within the cardiac intensive care unit, prompt recognition of severe acute valvular lesions is essential because hemodynamic collapse can occur rapidly, especially when cardiac chambers have not had time for compensatory remodeling. Within this context, optimal medical management, considerations for temporary mechanical circulatory support and decisive treatments strategies are addressed. Fundamental concepts include an appreciation for how sudden changes in flow and pressure gradients between cardiac chambers can impact hemodynamic and echocardiographic findings differently compared to similarly severe chronic lesions, as well as understanding the main causes for decompensated heart failure and cardiogenic shock for each valvular abnormality.

Partial Heart Transplantation - How to Change the System.

Partial heart transplantation is the first clinically successful approach to deliver growing heart valve implants. To date, 13 clinical partial heart transplants have been performed. However, turning partial heart transplantation into a routine procedure that is available to all children who would benefit from growing heart valve implants poses formidable logistical challenges. Firstly, a supply for partial heart transplant donor grafts needs to be developed. This challenge is complicated by the scarcity of donor organs. Importantly, the donor pools for orthotopic heart transplants, partial heart transplants and cadaver homografts overlap. Secondly, partial heart transplants need to be allocated. Factors relevant for equitable allocation include the indication, anatomical fit, recipient clinical status and time on the wait list. Finally, partial heart transplantation will require regulation and oversight, which only recently has been undertaken by the Food and Drug Administration, which regulates human cellular and tissue-based products. Overcoming these challenges will require a change in the system. Once this is achieved, partial heart transplantation could open new horizons for children who require growing tissue implants.

Imaging of Double Inlet Left Ventricle.

Double inlet left ventricle (DILV) is a form of single ventricle heart disease where both atrioventricular valves enter a single left ventricle. Surgical intervention may be needed in the neonatal period secondary to systemic outflow tract obstruction or less commonly pulmonary obstruction. Two-dimensional echocardiography can adequately assess newborn anatomy and define the need for surgery. Beyond the newborn period, there is a renewed interest in septation of DILV using intracardiac baffles in a staged approach. Cross sectional imaging can aid in surgical planning. This article will review common anatomic features of DILV and imaging considerations for both single ventricle palliation and DILV septation.

Long-term function of a novel autologous transcatheter pulmonary heart valve implant in an adult animal model.

BACKGROUND: Current heart valve implants entail major disadvantages in the treatment for younger patients or those with congenital heart defects. AIM: Evaluation of novel transcatheter pulmonary valve implant made from autologous pericardium with natural crosslinking agent in an in vitro setup and in vivo animal model METHODS: Valves were tested in a pulse duplicator according to ISO-standard 5840. For in vivo studies computer tomography was performed to measure sheep's native pulmonary valve dimensions. Pericardium was harvested by thoracotomy, personalized implants were manufactured and deployed in pulmonary valve position of the same sheep. Every 3 months implant functionality was evaluated by intracardiac echocardiography, intracardiac pressure measurements and cardiac magnetic resonance imaging (cMRI). Implants were explanted for macroscopic and histological examination. RESULTS: In vitro experiments showed compliance with regulatory requirements in terms of valve opening and insufficiency. Five sheep successfully received an autologous valve implant. Two animals had to be euthanized due to trauma sustained in the stable. Long-term valve function was excellent in three out of four animals with median implant cMRI regurgitation fraction of 9% (n = 4) at 3 months, 8% (n = 3) at 6, 8% (n = 3) at 9, 12% (n = 3) at 13, 8% (n = 2) at 17% and 8% (n = 2) at 20.5 months after implantation. Despite good adherence to neighboring tissue and endothelization, histological assessment revealed some signs of degeneration. CONCLUSION: Transcatheter pulmonary valve implants showed promising function for up to 20.5 months encouraging research to further improve this approach.

Randomized clinical trial of continuous transversus thoracis muscle plane block for patients undergoing open heart valve replacement surgery.

The optimal analgesia regimen after open cardiac surgery is unclear. The aim of this study was to investigate the beneficial effects of continuous transversus thoracis muscle plane (TTMP) blocks initiated before surgery on open cardiac surgery outcomes. A group of 110 patients were randomly allocated to either receive bilateral continuous TTMP blocks (TTP group) or no nerve block (SAL group). The primary endpoint was post-operative pain at 4, 8, 16, 24, 48 and 72 h after extubation at rest and exercise. The secondary outcome measures included analgesia requirements (sufentanil and flurbiprofen axetil administration), time to extubation, incidence of reintubation, length of stay in the ICU, incidence of post-operative nausea and vomiting (PONV), time until return of bowel function, time to mobilization, urinary catheter removal and length of hospital stay. The length of stay in the ICU and length of hospital stay were significantly longer in the SAL group than in the TTP group. NRS scores at rest and exercise were significantly lower in the TTP group than in the SAL group at all time points. The TTP group required significantly less intraoperative and post-operative sufentanil and post-operative dynastat consumption than the SAL group. Time to extubation, time to first flatus, time until mobilization and time until urinary catheter removal were significantly earlier in the TTP group than in the SAL group. The incidence of PONV was significantly lower in the TTP group. Bilateral continuous TTMP blocks provide effective analgesia and accelerate recovery in patients undergoing open heart valve replacement surgery.

Availability and threshold of the vasoactive-inotropic score for predicting early extubation in adults after rheumatic heart valve surgery: a single-center retrospective cohort study.

BACKGROUND: Early extubation (EEx) is defined as the removal of the endotracheal tube within 8 h postoperatively. The present study involved determining the availability and threshold of the vasoactive-inotropic score (VIS) for predicting EEx in adults after elective rheumatic heart valve surgery. METHODS: The present study was designed as a single-center retrospective cohort study which was conducted with adults who underwent elective rheumatic heart valve surgery with CPB. The highest VIS in the immediate postoperative period was used in the present study. The primary outcome, the availability of VIS for EEx prediction and the optimal threshold value were determined using ROC curve analysis. The gray zone analysis of the VIS was performed by setting the false negative or positive rate R = 0.05, and the perioperative risk factors for prolonged EEx were identified by multivariate logistic analysis. The postoperative complications and outcomes were compared between different VIS groups. RESULTS: Among the 409 patients initially screened, 379 patients were ultimately included in the study. The incidence of EEx was determined to be 112/379 (29.6%). The VIS had a good predictive value for EEx (AUC = 0.864, 95% CI: [0.828, 0.900], P < 0.001). The optimal VIS threshold for EEx prediction was 16.5, with a sensitivity of 71.54% (65.85-76.61%) and a specificity of 88.39% (81.15-93.09%). The upper and lower limits of the gray zone for the VIS were determined as (12, 17.2). The multivariate logistic analysis identified age (OR, 1.060; 95% CI: 1.017-1.106; P = 0.006), EF% (OR, 0.798; 95% CI: 0.742-0.859; P < 0.001), GFR (OR, 0.933; 95% CI: 0.906-0.961; P < 0.001), multiple valves surgery (OR, 4.587; 95% CI: 1.398-15.056; P = 0.012), and VIS > 16.5 (OR, 12.331; 95% CI: 5.015-30.318; P < 0.001) as the independent risk factors for the prolongation of EEx. The VIS ≤ 16.5 group presented a greater success rate for EEx, a shorter invasive ventilation support duration, and a lower incidence of complications than did the VIS > 16.5 group, while the incidence of reintubation was similar between the two groups. CONCLUSION: In adults, after elective rheumatic heart valve surgery, the highest VIS in the immediate postoperative period was a good predictive value for EEx, with a threshold of 16.5.

Association between gene polymorphisms and initial warfarin therapy in patients after heart valve surgery.

BACKGROUND: Warfarin is widely used for the prevention and treatment of thrombotic events. This study aimed to examine the influence of gene polymorphisms on the early stage of warfarin therapy in patients following heart valve surgery. METHODS: Nine single nucleotide polymorphisms were genotyped using microarray chips, categorizing patients into three groups: normal responders (Group I), sensitive responders (Group II), and highly sensitive responders (Group III). The primary clinical outcomes examined were time in therapeutic range (TTR) and international normalized ratio (INR) variability. To investigate potential influencing factors, a generalized linear regression model was employed. RESULTS: Among 734 patients, the prevalence of CYP2C9*3-1075A > C, CYP2C19*3-636G > A, and CYP2C19*17-806C > T variants were 11.2%, 9.9%, and 1.9% of patients, respectively. VKORC1-1639G > A or the linked -1173C > T variant was observed in 99.0% of the patients. Generalized linear model analysis revealed an impact of sensitivity grouping on INR variability. Compared to Group I, Group II showed higher TTR values (p = 0.023), while INR variability was poorer in Group II (p < 0.001) and Group III (p < 0.001). Individual gene analysis identified significant associations between CYP2C9*3-1075A > C (p < 0.001), VKORC1-1639G > A or the linked -1173 C > T (p = 0.009) and GGCX-3261G > A (p = 0.019) with INR variability. CONCLUSION: The genotypes of CYP2C9, VKORC1, and GGCX were found to have a significant impact on INR variability during the initial phase of warfarin therapy. However, no significant association was observed between TTR and gene polymorphisms. These findings suggest that focusing on INR variability is crucial in clinical practice, and preoperative detection of gene polymorphisms should be considered to assist in the initiation of warfarin therapy.

Comparison of two self-expanding transcatheter heart valves for degenerated surgical bioprostheses: the AVENGER multicentre registry.

BACKGROUND: There is a lack of comparative data on transcatheter aortic valve implantation (TAVI) in degenerated surgical prostheses (valve-in-valve [ViV]). AIMS: We sought to compare outcomes of using two self-expanding transcatheter heart valve (THV) systems for ViV. METHODS: In this retrospective multicentre registry, we included consecutive patients undergoing transfemoral ViV using either the ACURATE neo/neo2 (ACURATE group) or the Evolut R/PRO/PRO+ (EVOLUT group). The primary outcome measure was technical success according to Valve Academic Research Consortium (VARC)-3. Secondary outcomes were 30-day all-cause mortality, device success (VARC-3), coronary obstruction (CO) requiring intervention, rates of severe prosthesis-patient mismatch (PPM), and aortic regurgitation (AR) ≥moderate. Comparisons were made after 1:1 propensity score matching. RESULTS: The study cohort comprised 835 patients from 20 centres (ACURATE n=251; EVOLUT n=584). In the matched cohort (n=468), technical success (ACURATE 92.7% vs EVOLUT 88.9%; p=0.20) and device success (69.7% vs 73.9%; p=0.36) as well as 30-day mortality (2.8% vs 1.6%; p=0.392) were similar between the two groups. The mean gradients and rates of severe PPM, AR ≥moderate, or CO did not differ between the groups. Technical and device success were higher for the ACURATE platform among patients with a true inner diameter (ID) >19 mm, whereas a true ID ≤19 mm was associated with higher device success - but not technical success - among Evolut recipients. CONCLUSIONS: ViV TAVI using either ACURATE or Evolut THVs showed similar procedural outcomes. However, a true ID >19 mm was associated with higher device success among ACURATE recipients, whereas in patients with a true ID ≤19 mm, device success was higher when using Evolut.

Redo-TAVI with the ACURATE neo2 and Prime XL for balloon-expandable transcatheter heart valve failure.

BACKGROUND: There are limited data regarding treatment for failed balloon-expandable transcatheter heart valves (THVs) in redo-transcatheter aortic valve implantation (TAVI). AIMS: We aimed to assess THV performance, neoskirt height and expansion when performing redo-TAVI with the ACURATE platform inside a SAPIEN 3 (S3) compared to redo-TAVI with an S3 in an S3. METHODS: Redo-TAVI was performed on the bench using each available size of the S3, the ACURATE neo2 (ACn2) and the next-generation ACURATE Prime XL (AC XL) implanted at 2 different depths within 20 mm/23 mm/26 mm/29 mm S3s serving as the "failed" index THV. Hydrodynamic testing was performed to assess THV function. Multimodality assessment was performed using photography, X-ray, microcomputed tomography (micro-CT), and high-speed videos. RESULTS: The ACURATE in S3 combinations had favourable hydrodynamic performance compared to the S3 in S3 for all size combinations. In the 20 mm S3, redo-TAVI with the ACn2 had lower gradients compared to the S3 (mean gradient 16.3 mmHg for the ACn2 vs 24.7 mmHg for the 20 mm S3 in 20 mm S3). Pinwheeling was less marked for the ACURATE THVs than for the S3s. On micro-CT, the S3s used for redo-TAVI were underexpanded across all sizes. This was also observed for the ACURATE platform, but to a lesser extent. CONCLUSIONS: Redo-TAVI with an ACn2/AC XL within an S3 has favourable hydrodynamic performance and less pinwheeling compared to an S3 in S3. This comes at the price of a taller neoskirt.

Double crosslinking decellularized bovine pericardium of dialdehyde chondroitin sulfate and zwitterionic copolymer for bioprosthetic heart valves with enhanced antithrombogenic, anti-inflammatory and anti-calcification properties.

Due to the increasing aging population and the advancements in transcatheter aortic valve replacement (TAVR), the use of bioprosthetic heart valves (BHVs) in patients diagnosed with valvular disease has increased substantially. Commercially available glutaraldehyde (GA) cross-linked biological valves suffer from reduced durability due to a combination of factors, including the high cell toxicity of GA, subacute thrombus, inflammation and calcification. In this study, oxidized chondroitin sulfate (OCS), a natural polysaccharide derivative, was used to replace GA to cross-link decellularized bovine pericardium (DBP), carrying out the first crosslinking of DBP to obtain OCS-BP. Subsequently, the zwitterion radical copolymerization system was introduced in situ to perform double cross-linking to obtain double crosslinked BHVs with biomimetic modification (P(APM/MPC)-OCS-BP). P(APM/MPC)-OCS-BP presented enhanced mechanical properties, collagen stability and enzymatic degradation resistance due to double crosslinking. The ex vivo AV-shunt assay and coagulation factors test suggested that P(APM/MPC)-OCS-BP exhibited excellent anticoagulant and antithrombotic properties due to the introduction of P(APM/MPC). P(APM/MPC)-OCS-BP also showed good HUVEC-cytocompatibility due to the substantial reduction of its residual aldehyde group. The subcutaneous implantation also demonstrated that P(APM/MPC)-OCS-BP showed a weak inflammatory response due to the anti-inflammatory effect of OCS. Finally, in vivo and in vitro results revealed that P(APM/MPC)-OCS-BP exhibited an excellent anti-calcification property. In a word, this simple cooperative crosslinking strategy provides a novel solution to obtain BHVs with good mechanical properties, and HUVEC-cytocompatibility, anti-coagulation, anti-inflammatory and anti-calcification properties. It might be a promising alternative to GA-fixed BP and exhibited good prospects in clinical applications.

Cardiac Valve Event Timing in Echocardiography Using Deep Learning and Triplane Recordings.

Cardiac valve event timing plays a crucial role when conducting clinical measurements using echocardiography. However, established automated approaches are limited by the need of external electrocardiogram sensors, and manual measurements often rely on timing from different cardiac cycles. Recent methods have applied deep learning to cardiac timing, but they have mainly been restricted to only detecting two key time points, namely end-diastole (ED) and end-systole (ES). In this work, we propose a deep learning approach that leverages triplane recordings to enhance detection of valve events in echocardiography. Our method demonstrates improved performance detecting six different events, including valve events conventionally associated with ED and ES. Of all events, we achieve an average absolute frame difference (aFD) of maximum 1.4 frames (29 ms) for start of diastasis, down to 0.6 frames (12 ms) for mitral valve opening when performing a ten-fold cross-validation with test splits on triplane data from 240 patients. On an external independent test consisting of apical long-axis data from 180 other patients, the worst performing event detection had an aFD of 1.8 (30 ms). The proposed approach has the potential to significantly impact clinical practice by enabling more accurate, rapid and comprehensive event detection, leading to improved clinical measurements.

Pregnancy outcomes in Chinese women with mechanical heart valves receiving warfarin treatment throughout pregnancy: 14-year experience.

OBJECTIVE: The purpose was to evaluate pregnancy outcomes and risk factors associated with fetal complications in Chinese pregnant women with mechanical heart valves (MHVs) taking low-dose warfarin, aiming to fill in the research gap of this area. METHODS: Between June 2010 and Aug 2023, 122 patients with MHVs who had 151 pregnancies and received warfarin throughout pregnancy were included. We compared them with 302 paired pregnancies without warfarin treatment. Binary logistic regression analyses were performed to explore risk predictors of fetal complications. RESULTS: Pregnancy loss rate was 37.1 % in women taking warfarin, compared to only 4.6 % for those without warfarin exposure in pregnancy (RR = 8.00, 95 % CI: 4.61-13.90). In pregnant women with MHVs, there were 34 spontaneous abortions, 22 stillbirths and 1 neonatal malformation. In the first, second and third pregnant trimesters of women with MHVs, fetal complication incidences were 19.2 %, 9.9 % and 8.0 %, respectively. 86.0 % of fetal complications occurred in women taking a warfarin dose ≤5 mg/d, accounting for 94.0 % of the total population. The newborns' birth weight, gestational age and 1-minute Apgar score were significantly lower in pregnancies treated with warfarin compared to those without warfarin exposure. Only 2.0 % of postpartum hemorrhage and no thrombosis or maternal mortality data were collected in pregnant women on warfarin in this study. CONCLUSION: Most Chinese pregnant women take a warfarin daily dose ≤5 mg and they might have only around 60 % chance of giving birth to a live baby without maternal complications.

Healthcare exposures and associated risk of endocarditis after open-heart cardiac valve surgery.

BACKGROUND: Infective endocarditis (IE) following cardiac valve surgery is associated with high morbidity and mortality. Data on the impact of iatrogenic healthcare exposures on this risk are sparse. This study aimed to investigate risk factors including healthcare exposures for post open-heart cardiac valve surgery endocarditis (PVE). METHODS: In this population-linkage cohort study, 23,720 patients who had their first cardiac valve surgery between 2001 and 2017 were identified from an Australian state-wide hospital-admission database and followed-up to 31 December 2018. Risk factors for PVE were identified from multivariable Cox regression analysis and verified using a case-crossover design sensitivity analysis. RESULTS: In 23,720 study participants (median age 73, 63% male), the cumulative incidence of PVE 15 years after cardiac valve surgery was 7.8% (95% CI 7.3-8.3%). Thirty-seven percent of PVE was healthcare-associated, which included red cell transfusions (16% of healthcare exposures) and coronary angiograms (7%). The risk of PVE was elevated for 90 days after red cell transfusion (HR = 3.4, 95% CI 2.1-5.4), coronary angiogram (HR = 4.0, 95% CI 2.3-7.0), and healthcare exposures in general (HR = 4.0, 95% CI 3.3-4.8) (all p < 0.001). Sensitivity analysis confirmed red cell transfusion (odds ratio [OR] = 3.9, 95% CI 1.8-8.1) and coronary angiogram (OR = 2.6, 95% CI 1.5-4.6) (both p < 0.001) were associated with PVE. Six-month mortality after PVE was 24% and was higher for healthcare-associated PVE than for non-healthcare-associated PVE (HR = 1.3, 95% CI 1.1-1.5, p = 0.002). CONCLUSIONS: The risk of PVE is significantly higher for 90 days after healthcare exposures and associated with high mortality.

Predictive Role of Preoperative Nutritional Status on Early Postoperative Outcomes in Different-Aged Patients Undergoing Heart Valve Surgery.

OBJECTIVES: The authors sought to elucidate the role and predictive effects of preoperative nutritional status on postoperative outcomes across different age groups undergoing heart valve surgery. DESIGN: A retrospective study with intergroup comparison, receiver operating characteristic curve analysis, and logistic regression analysis. SETTING: A hospital affiliated with a medical university. PARTICIPANTS: Three thousand nine hundred five patients undergoing heart valve surgery between October 2016 and December 2020. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patients were categorized into 3 age subgroups: young (aged 18-44 years), middle-aged (aged 45-59 years), and older (aged ≥60 years) adults. The Nutritional Risk Index (NRI), Prognostic Nutritional Index, and Controlling Nutritional Status scores were evaluated. Young adults with an NRI <99 experienced a significantly higher rate of prolonged intensive care unit stay (28.3% v 4.1%, p < 0.001), with a relative risk of 4.58 (95% CI: 2.04-10.27). Similarly, young adults with an NRI <97 had a significantly increased occurrence of mortality within 30 days after surgery (6.3% v 0.2%, p < 0.001), with a relative risk of 41.11 (95% CI: 3.19-529.48). CONCLUSIONS: In patients who undergo heart valve surgery, early postoperative outcomes can be influenced by nutritional status before the surgery. In the young-adult group, NRI <99 and NRI <97 effectively could predict prolonged intensive care unit stay and 30-day mortality, respectively.

Directed Differentiation of Human Induced Pluripotent Stem Cells to Heart Valve Cells.

BACKGROUND: A main obstacle in current valvular heart disease research is the lack of high-quality homogeneous functional heart valve cells. Human induced pluripotent stem cells (hiPSCs)-derived heart valve cells may help with this dilemma. However, there are no well-established protocols to induce hiPSCs to differentiate into functional heart valve cells, and the networks that mediate the differentiation have not been fully elucidated. METHODS: To generate heart valve cells from hiPSCs, we sequentially activated the Wnt, BMP4, VEGF (vascular endothelial growth factor), and NFATc1 signaling pathways using CHIR-99021, BMP4, VEGF-165, and forskolin, respectively. The transcriptional and functional similarity of hiPSC-derived heart valve cells compared with primary heart valve cells were characterized. Longitudinal single-cell RNA sequencing was used to uncover the trajectory, switch genes, pathways, and transcription factors of the differentiation. RESULTS: An efficient protocol was developed to induce hiPSCs to differentiate into functional hiPSC-derived valve endothelial-like cells and hiPSC-derived valve interstitial-like cells. After 6-day differentiation and CD144 magnetic bead sorting, ≈70% CD144+ cells and 30% CD144- cells were obtained. On the basis of single-cell RNA sequencing data, the CD144+ cells and CD144- cells were found to be highly similar to primary heart valve endothelial cells and primary heart valve interstitial cells in gene expression profile. Furthermore, CD144+ cells had the typical function of primary heart valve endothelial cells, including tube formation, uptake of low-density lipoprotein, generation of endothelial nitric oxide synthase, and response to shear stress. Meanwhile, CD144- cells could secret collagen and matrix metalloproteinases, and differentiate into osteogenic or adipogenic lineages like primary heart valve interstitial cells. Therefore, we identified CD144+ cells and CD144- cells as hiPSC-derived valve endothelial-like cells and hiPSC-derived valve interstitial-like cells, respectively. Using single-cell RNA sequencing analysis, we demonstrated that the trajectory of heart valve cell differentiation was consistent with embryonic valve development. We identified the main switch genes (NOTCH1, HEY1, and MEF2C), signaling pathways (TGF-ß, Wnt, and NOTCH), and transcription factors (MSX1, SP5, and MECOM) that mediated the differentiation. Finally, we found that hiPSC-derived valve interstitial-like cells might derive from hiPSC-derived valve endothelial-like cells undergoing endocardial-mesenchymal transition. CONCLUSIONS: In summary, this is the first study to report an efficient strategy to generate functional hiPSC-derived valve endothelial-like cells and hiPSC-derived valve interstitial-like cells from hiPSCs, as well as to elucidate the differentiation trajectory and transcriptional dynamics of hiPSCs differentiated into heart valve cells.