A transformer-based diffusion probabilistic model for heart rate and blood pressure forecasting in Intensive Care Unit.

BACKGROUND AND OBJECTIVE: Vital sign monitoring in the Intensive Care Unit (ICU) is crucial for enabling prompt interventions for patients. This underscores the need for an accurate predictive system. Therefore, this study proposes a novel deep learning approach for forecasting Heart Rate (HR), Systolic Blood Pressure (SBP), and Diastolic Blood Pressure (DBP) in the ICU. METHODS: We extracted 24,886 ICU stays from the MIMIC-III database which contains data from over 46 thousand patients, to train and test the model. The model proposed in this study, Transformer-based Diffusion Probabilistic Model for Sparse Time Series Forecasting (TDSTF), merges Transformer and diffusion models to forecast vital signs. The TDSTF model showed state-of-the-art performance in predicting vital signs in the ICU, outperforming other models' ability to predict distributions of vital signs and being more computationally efficient. The code is available at https://github.com/PingChang818/TDSTF. RESULTS: The results of the study showed that TDSTF achieved a Standardized Average Continuous Ranked Probability Score (SACRPS) of 0.4438 and a Mean Squared Error (MSE) of 0.4168, an improvement of 18.9% and 34.3% over the best baseline model, respectively. The inference speed of TDSTF is more than 17 times faster than the best baseline model. CONCLUSION: TDSTF is an effective and efficient solution for forecasting vital signs in the ICU, and it shows a significant improvement compared to other models in the field.

TEA domain transcription factor 1(TEAD1) induces cardiac fibroblasts cells remodeling through BRD4/Wnt4 pathway.

Cardiac fibroblasts (CFs) are the primary cells tasked with depositing and remodeling collagen and significantly associated with heart failure (HF). TEAD1 has been shown to be essential for heart development and homeostasis. However, fibroblast endogenous TEAD1 in cardiac remodeling remains incompletely understood. Transcriptomic analyses revealed consistently upregulated cardiac TEAD1 expression in mice 4 weeks after transverse aortic constriction (TAC) and Ang-II infusion. Further investigation revealed that CFs were the primary cell type expressing elevated TEAD1 levels in response to pressure overload. Conditional TEAD1 knockout was achieved by crossing TEAD1-floxed mice with CFs- and myofibroblasts-specific Cre mice. Echocardiographic and histological analyses demonstrated that CFs- and myofibroblasts-specific TEAD1 deficiency and treatment with TEAD1 inhibitor, VT103, ameliorated TAC-induced cardiac remodeling. Mechanistically, RNA-seq and ChIP-seq analysis identified Wnt4 as a novel TEAD1 target. TEAD1 has been shown to promote the fibroblast-to-myofibroblast transition through the Wnt signalling pathway, and genetic Wnt4 knockdown inhibited the pro-transformation phenotype in CFs with TEAD1 overexpression. Furthermore, co-immunoprecipitation combined with mass spectrometry, chromatin immunoprecipitation, and luciferase assays demonstrated interaction between TEAD1 and BET protein BRD4, leading to the binding and activation of the Wnt4 promoter. In conclusion, TEAD1 is an essential regulator of the pro-fibrotic CFs phenotype associated with pathological cardiac remodeling via the BRD4/Wnt4 signalling pathway.

Electrospun compliant heparinized elastic vascular graft for improving the patency after implantation.

The low patency rate after artificial blood vessel replacement is mainly due to the ineffective use of anticoagulant factors and the mismatch of mechanical compliance after transplantation. Electrospun nanofibers with biomimetic extracellular matrix three-dimensional structure and tunable mechanical strength are excellent carriers for heparin. In this work, we have designed and synthesized a series of biodegradable poly(ester-ether-urethane)ureas (BEPU), following compound with optimized constant concentration of heparin by homogeneous emulsion blending, then spun into the hybrid BEPU/heparin nanofibers tubular graft for replacing rats' abdominal aorta in situ for comprehensive performance evaluation. The results in vitro demonstrated that the electrospun L-PEUUH (LDI-based PEUU with heparin) vascular graft was of regular microstructure, optimum surface wettability, matched mechanical properties, reliable cytocompatibility, and strongest endothelialization in situ. Replacement of resected abdominal artery with the L-PEUUH vascular graft in rat showed that the graft was capable of homogeneous hybrid heparin and significantly promoted the stabilization of vascular endothelial cells (VECs) and vascular smooth muscle cells (VSMCs), as well as stabilizing the blood microenvironment. This research demonstrates the L-PEUUH vascular graft with substantial patency, indicating their potential for injured vascular healing.

Development of an interactive web dashboard to facilitate the reexamination of pathology reports for instances of underbilling of CPT codes.

Current Procedural Terminology Codes is a numerical coding system used to bill for medical procedures and services and crucially, represents a major reimbursement pathway. Given that pathology services represent a consequential source of hospital revenue, understanding instances where codes may have been misassigned or underbilled is critical. Several algorithms have been proposed that can identify improperly billed CPT codes in existing datasets of pathology reports. Estimation of the fiscal impacts of these reports requires a coder (i.e., billing staff) to review the original reports and manually code them again. As the re-assignment of codes using machine learning algorithms can be done quickly, the bottleneck in validating these reassignments is in this manual re-coding process, which can prove cumbersome. This work documents the development of a rapidly deployable dashboard for examination of reports that the original coder may have misbilled. Our dashboard features the following main components: (1) a bar plot to show the predicted probabilities for each CPT code, (2) an interpretation plot showing how each word in the report combines to form the overall prediction, and (3) a place for the user to input the CPT code they have chosen to assign. This dashboard utilizes the algorithms developed to accurately identify CPT codes to highlight the codes missed by the original coders. In order to demonstrate the function of this web application, we recruited pathologists to utilize it to highlight reports that had codes incorrectly assigned. We expect this application to accelerate the validation of re-assigned codes through facilitating rapid review of false-positive pathology reports. In the future, we will use this technology to review thousands of past cases in order to estimate the impact of underbilling has on departmental revenue.

A novel deletion mutation accompanied by a point mutation in Lamin A/C gene: Screened from a dilated cardiomyopathy family.

BACKGROUND: There are 30%-40% of patients with dilated cardiomyopathy (DCM) having genetic causes, among which Lamin A and C gene (LMNA) mutation is the second most frequent DCM-related mutation, and Lamin A/C may be involved in the pathogenesis of DCM through the regulation of gene transcription or the direct effect of cell structure. Methods: Echocardiography and electrocardiogram were used to diagnose DCM and arrhythmia in a DCM family. Then, linked mutations on LMNA were screened out by high-throughput sequencing and verified by Sanger sequencing in all research individuals. Meanwhile, Human Genome Variation Society (HGVS) and Integrative Genomics Viewer (IGV) were used to analyse the characteristics of the mutated Lamin A/C protein. Finally, mutated-type and wild-type LMNA plasmid was transfected into AC-16 cardiomyocytes with the form of a lentivirus vector, and its effect on nucleus and actin was studied by immunofluorescence detection. RESULTS: In this study, we found a new frame-shifted mutation of LMNA (p.Ser414Alafs*66) linked with another point mutation from a DCM family by using High-throughput sequencing, and this deletion mutation led to a truncation of Lamin A/C. By analysing the clinical characteristics of this DCM family, we found that all DCM patients with arrhythmia were carriers of this co-segregation mutation. In the cytological experiment, we found that the mutated-type transfections showed weaker fluorescent intensities on both actin and cell nucleus. CONCLUSIONS: A co-segregation mutation of LMNA (Point mutation chr1 156107548 c.1712 G>A and truncated frame-shifted mutation chr1 156106086 c.1240delA) was found from a DCM family, and this type of mutation could participate in the pathogenesis of DCM by affecting the expression of actin.

Evaluation of electrospun PCL diol-based elastomer fibers as a beneficial matrix for vascular tissue engineering.

The main reason for the failure of artificial blood vessel transplantation is the lack of mechanically matched materials with excellent blood compatibility. The electrospun biodegradable polyurethane (BPU) fibers with micro to nanoscale topography and high porosity similar to the natural extracellular matrix (ECM) is one of the most suitable options for vascular graft. In our recent study, we prepared a series of PCL-based BPU fibers by combining two-step solution polymerization and electrospinning. SEM, 1H NMR, ATR-FTIR, XRD, TG, water contact angle, and mechanical tests were used to analyze the chemical structure, microstructure, thermal properties, surface wettability, degradation, cytocompatibility, and hemocompatibility in vitro of electrospun fibers. The results show that the synthesized H-PEUU, L-PEUU, H-PEEUU, and L-PEEUU have different crystalline properties, thus exhibiting distinctive thermal, mechanical, and degradation properties. Although the existence of the molecular structure of LDI and PEG600 in fibers can promote cell proliferation and migration unilaterally, the microstructure of the material is also the main factor affecting the biocompatibility of cells. The results suggest that the designed PCL-based degradable polyurethane electrospun fiber is expected to be applied to vascular tissue engineering.

Electrospun PCL/collagen hybrid nanofibrous tubular graft based on post-network bond processing for vascular substitute.

Inhibiting thrombus formation and intimal hyperplasia is essential for orthotopic tissue-engineered vascular grafts. The matching mechanical properties of autologous blood vessels and inhibition of platelet aggregation are considered as two points to improve the success rate of transplantation. The poly(ε-caprolactone)/collagen/heparin composite vascular graft (PCLHC) with three-dimensional network structure were constructed by electrospinning, which can mimic natural vascular biomechanics and enhance the viability of cells viability in vitro. The hybrid collagen matrix network nanofibers formed by electrospinning exhibited uniform and smooth morphology. The results of mechanical experiments showed that PCLHC had similar mechanical properties to natural blood vessels. And the addition of heparin enhanced the anticoagulation of PCLHC. Simultaneous three-component hybrid nanofibers showed a potentially reliable ability to promote the proliferation of human umbilical vein endothelial cells (HUVECs). In summary, all the results showed that the three-dimensional network structure of PCLHC presented the potential to heal injured vessels.

Circulating soluble receptor of advanced glycation end product is associated with bicuspid aortic aneurysm progression via NF-κB pathway.

OBJECTIVES: Patients with bicuspid aortic valve (BAV) have a high risk of aortic dilation and adverse vascular events. Previous studies had reported soluble receptor for advanced glycation end products (sRAGE) to compete with receptor of advanced glycation end products (RAGE) for ligand binding and inhibit the activation of nuclear-factor kappa-B (NF-κB) pathway and matrix metalloproteinases (MMP) transcription. Thus, sRAGE serum levels may contribute to the clinical diagnosis and monitoring of ascending aorta aneurysm in patients with BAV. METHODS: To eliminate the confounding factors, 44 patients with BAV were divided into 3 subgroups according to the diameter of ascending aorta, and 20 patients with tricuspid aortic valve and normal-sized ascending aorta were selected as a control group. Protein levels and gene transcription of several variates were evaluated in the tissue and serum samples from these patients. Human aortic smooth muscle cells were treated with AGE-BSA in gradient concentrations, and changes in phenotype and protein and mRNA levels were detected. RESULTS: Serum levels of sRAGE in the 3 BAV groups were obviously higher than those in the tricuspid aortic valve group, although there was negative correlation between the serum sRAGE levels and ascending aortic diameters among patients with BAV. Transcript expression levels of RAGE and NF-κBp65 mRNA were increased in the 3 BAV groups and RAGE/NF-κB pathway was activated with the progression of ascending aortic aneurysm. Abnormal activation of RAGE/NF-κB pathway was observed in AGE-BSA-treated human aortic smooth muscle cells. CONCLUSIONS: Our study has shown a trend in serum levels of sRAGE among patients with BAV, and that the cellular and extracellular pathological processes are quite serious even in the normal-sized or slightly dilated aorta. Together, the findings indicated that sRAGE may be used as a biomarker to predict aneurysm expansion rates and the risk of adverse vascular events.

Long-Term Outcomes of Surgical Treatment for Acute Type-A Aortic Dissection with Coronary Artery Involvement.

The surgical strategies for acute type-A aortic dissection (aTAAD) with coronary artery involvement have been controversial, and its prognosis remains unclear. Thus, in this study, we aim to determine the characteristics, surgical strategies, and prognosis of patients with coronary artery involvement due to aTAAD.Retrospective analysis of 65 consecutive aTAAD patients with coronary artery involvement between September 2005 and January 2012 was performed. The patients were divided into two groups: those treated with aTAAD repair and coronary ostia reimplantation (Neri type-A, group A, n = 37) and those with aTAAD repair and coronary artery bypass grafting (Neri type B and C, group B, n = 28).Overall in-hospital mortality was determined to be 8.1% for group A and 21.4% for group B (P = 0.124). No significant difference was determined between groups A and B in cardiopulmonary bypass time, cross-clamp time, cerebral perfusion time, and hospitalization time. Intensive care unit (ICU) stay was 5.8 ± 7.4 days for group A, whereas it was 12.4 ± 10.6 days for group B (P = 0.009). The morbidity of postoperative temporary and permanent neurological dysfunction was similar between the two groups, while renal and respiratory dysfunction were 8.1% versus 25.0% and 16.2% versus 39.3%, respectively (P = 0.062, P = 0.036). Average follow-up time was 112.0 ± 44.8 months, and survival curves have not shown statistical significance between two groups (P = 0.386).Coronary artery dissection with Neri type B and C in acute TAAD has been associated with higher early death, but comparable long-term survival after discharge. However, combined immediate coronary artery bypass grafting and aortic repair remains a safe, effective, and acceptable approach to these challenging group of patients.

MicroRNAs involve in bicuspid aortic aneurysm: pathogenesis and biomarkers.

The incidence of bicuspid aortic valves (BAV) is high in the whole population, BAV-related thoracic aortic aneurysm (TAA) is accompanied by many adverse vascular events. So far, there are two key points in dealing with BAV-related TAA. First is fully understanding on its pathogenesis. Second is optimizing surgical intervention time. This review aims to illustrate the potential role of miRNAs in both aspects, that is, how miRNAs are involved in the occurrence and progression of BAV-related TAA, and the feasibilities of miRNAs as biomarkers.

Identification of Differently Expressed mRNAs in Atherosclerosis Reveals CDK6 Is Regulated by circHIPK3/miR-637 Axis and Promotes Cell Growth in Human Vascular Smooth Muscle Cells.

Atherosclerosis is the leading cause of heart disease and stroke, and one of the leading causes of death and disability worldwide. The phenotypic transformation of vascular smooth muscle cells (VSMCs) plays an important role in the pathological process of atherosclerosis. The present study aimed to identify differently expressed mRNAs in atherosclerosis by analyzing GSE6088 database. Our results revealed there were totally 467 increased and 490 decreased differential expressed genes (DEGs) in atherosclerosis. Bioinformatics analysis demonstrated that the DEGs substantially existed in pathways, including Glyoxylate and dicarboxylate metabolism, Tyrosine metabolism, Tryptophan metabolism, Beta-Alanine metabolism, Fatty acid biosynthesis and Starch and sucrose metabolism. Next, we constructed a protein-protein interaction (PPI) network to identify hub genes in atherosclerosis. Also, we identified CDK6 as a key regulator of atherosclerosis. In this study, we found that CDK6 knockdown suppressed HASMC and HUASMC cell proliferation. Circular RNA (CircRNA) is a non-coding RNA which is reported to have an unusual influence on tumorigenesis process and other aspects in the last few years. Previous studies showed circRNAs could act as miRNAs sponging in multiple biological processes. Bioinformatics prediction and luciferase analysis showed that CDK6 were targeted and regulated by circHIPK3/miR-637. Moreover, silencing circHIPK3 could also significantly induce the arrest and apoptosis of cell cycle. In conclusion, this study discovered the important regulatory role of circHIPK3 in the proliferation and apoptosis of VSMCs by influencing the miR-637/CDK6 axis.

Construction and performance evaluation of Hep/silk-PLCL composite nanofiber small-caliber artificial blood vessel graft.

To meet the growing clinical demand for small-caliber blood vessel grafts to treat cardiovascular diseases, it is necessary to develop safe and long-term unobstructed grafts. In this study, a biodegradable graft made of composite nanofibers is introduced. A composite nanofiber core-shell structure was prepared by a combination of conjugate electrospinning and freeze-dry technology. The core fiber was poly(l-lactide-co-caprolactone) (PLCL)-based and the core fibers were coated with heparin/silk gel, which acted as a shell layer. This special structure in which the core layer was made of synthetic materials and the shell layer was made of natural materials took advantage of these two different materials. The core PLCL nanofibers provided mechanical support during vascular reconstruction, and the shell heparin/silk gel layer enhanced the biocompatibility of the grafts. Moreover, the release of heparin in the early stage after transplantation could regulate the microenvironment and inhibit the proliferation of intima. All of the graft materials were biodegradable and safe biomaterials, and the degradation of the graft provided space for the growth of regenerated tissue in the late stage of transplantation. Animal experiments showed that the graft remained unobstructed for more than eight months in vivo. In addition, the regenerated vascular tissue provided a similar function to that of autogenous vascular tissue when the graft was highly degraded. Thus, the proposed method produced a graft that could maintain long-term patency in vivo and remodel vascular tissue successfully.

Simplified, minimally invasive, beating-heart technique for redo isolated tricuspid valve surgery.

BACKGROUND: Redo isolated tricuspid valve surgery is associated with a high morbidity and mortality, and its optimal timing remains controversial. Hence, here we reviewed the early and midterm results of simplified, minimally invasive, beating-heart technique for redo isolated tricuspid valve surgery in patients at high risk. METHODS: A total of 32 consecutive patients underwent a redo isolated tricuspid valve surgery using minimally invasive, beating-heart technique through a right lateral thoracotomy in our center between June 2016 and April 2020. The mean age of patients was 57.4 ± 8.3 years, and 18 patients (56.3%) were women. The mean preoperative EuroSCORE was 7.8 ± 1.4 (range: 6-11). Follow-up was 87.1% complete, with a mean duration of 26.3 ± 12.3 months. RESULTS: Both in-hospital and 30-day mortalities were 3.1%. Tricuspid valve replacement with bioprosthesis was performed in 30 patients (93.8%), and the remaining two patients (6.2%) underwent tricuspid repair (annuloplasty and leaflet reconstruction). The mean cardiopulmonary bypass time was 81.5 ± 29.0 min. The overall in-hospital duration and intensive care unit (ICU) times were 13.6 ± 7.6 days and 4.1 ± 2.8 days, respectively. Postoperative complications included prolonged ventilation in six patients (18.8%), acute kidney injury in three patients (9.4%), and neurologic event, wound infection, or permanent third-degree atrioventricular block, in one patient (3.1%) each. A total of 96.9% patients were discharged uneventfully. Four patients were lost to follow-up; there were no midterm deaths in patients who were followed up. CONCLUSIONS: Simplified, minimally invasive, beating-heart technique for redo tricuspid valve surgery is both feasible and safe, and the early and midterm results are excellent.

LncRNA LOXL1-AS is up-regulated in thoracic aortic aneurysm and regulated proliferation and apoptosis of aortic smooth muscle cells.

Long non-coding RNA LOXL1-AS is up-regulated in several types of cancers. The present study was carried out to explore the potential interactions between LOXL1-AS and lncRNA Giver in thoracic aortic aneurysm (TAA). We found that LOXL1-AS was up-regulated in TAA patients than in healthy controls in aortic media specimens. Altered expression levels of LOXL1-AS distinguished TAA patients from healthy controls. LncRNA Giver was also up-regulated in TAA patients than in healthy controls in aortic media specimens, and was positively correlated with LOXL1-AS. LOXL1-AS overexpression mediated the up-regulation of Giver in human aortic smooth muscle cells, while Giver overexpression failed to significantly affect LOXL1-AS. LOXL1-AS and Giver overexpression resulted in promoted proliferation and inhibited apoptosis of HAOSMC. Giver silencing played an opposite role and attenuated the effect of LOXL1-AS overexpression. Therefore, LOXL1-AS was up-regulated in TAA and regulated proliferation and apoptosis of LOXL1-AS by up-regulating Giver.

Electrospun Bilayer Composite Vascular Graft with an Inner Layer Modified by Polyethylene Glycol and Haparin to Regenerate the Blood Vessel.

In this study, we prepared a composite vascular graft with two layers. The inner layer, which was comprised of degradable Poly(lactic-co-glycolic acid) (PLGA)/Collagen (PC) nanofibers modified by mesoporous silica nanoparticles (MSN), was grafted with polyethylene glycol (PEG) and heparin to promote cell proliferation and to improve blood compatibility. The outer layer was comprised of polyurethane (PU) nanofibers in order to provide mechanical support. The growth and proliferation of human umbilical vein endothelial cells (HUVECs) in the inner layer was significant, and blood compatibility testing showed that the inner layer had good blood compatibility. The MSN-PEG-Heparin on the fiber surface was observed in vitro during the degradation of the inner layer. After 60 days, the weight of fiber membrane decreased by 92.4%. The inner layer did not cause an inflammatory reaction during the degradation process in vivo and there was uniform cellular growth on the PC/MSN-PEG-Heparin fiber membrane. Composite grafts implanted into the rabbit carotid artery were evaluated for 8 weeks by H&E and immunohistochemical staining, demonstrating that a monolayer of endothelium (CD31-labeled) and smooth muscle (αSMA-labeled) regenerated on the composite graft. Our results demonstrate that the composite graft, with a functional inner layer, has potential to be used for small-caliber blood vessels with long-term patency.

A Method for Preparation of an Internal Layer of Artificial Vascular Graft Co-Modified with Salvianolic Acid B and Heparin.

Studies have shown that salvianolic acid B (SAB), which is derived from Chinese salvia ( Salvia miltiorrhiza), a plant used in traditional Chinese medicine, can promote the proliferation and migration of endothelial cells. The inner layer of an artificial vascular graft was fabricated using the coaxial electrospinning method and was loaded with the anticoagulant heparin and SAB. The release of heparin and SAB was sustained for almost 30 days and without an initial burst release of SAB. Furthermore, the combined effect of SAB and heparin contributed to promoting human umbilical vein endothelial cell (HUVEC) growth and improved the blood compatibility of the graft. In addition, upregulation of GRP78 by SAB protected human endothelial cells from oxidative stress-induced cellular damage. In vivo evaluation through Masson's trichrome and H&E staining was performed after the graft was subcutaneously embedded in SD rats for 2 weeks and indicated that the graft possessed satisfactory biocompatibility and did not cause a significant immune response. Hence, the functional inner layer is promising for preventing acute thrombosis and promotes rapid endothelialization of artificial vascular grafts.

hsa-miR-320d and hsa-miR-582, miRNA Biomarkers of Aortic Dissection, Regulate Apoptosis of Vascular Smooth Muscle Cells.

Abnormal expression of microRNAs (miRNAs) has been associated with aortic dissection (AD). Next-generation sequencing was performed to identify the differentially expressed miRNAs in aortic tissue samples between AD and nondiseased individuals. Selected miRNAs, which showed significant variation between the 2 groups, were then transfected into human aortic vascular smooth muscle cells, and assessed for effects on cell migration and induced apoptosis. The changes in gene expression pattern in human aortic vascular smooth muscle cells transfected with the miRNAs were also investigated. Among the 314 miRNAs detected in the aortic tissues from both AD and normal subjects, 46 showed significantly different expression patterns. Only 7 of these differentially expressed miRNAs were found to be enriched in AD, whereas the majority had diminished. hsa-miR-320d and hsa-miR-582 were 2 representative miRNAs that exhibited a decrease of greater than 10-fold. Transfection of hsa-miR-320d and hsa-miR-582 did not affect the migration capability of the vascular smooth muscle cells, but remarkably enhanced the staurosporine and tumor necrosis factor-α-induced apoptosis by 15% and 29%, respectively. Furthermore, the transfection of both miRNAs affected the expression of a vast multitude of genes, most of which were related to apoptotic pathways. The fluorescence reporter assays demonstrated that hsa-miR-320d and hsa-miR-582 bind the 3' UTR region of TRIAP1 and NET1 genes, respectively. These results suggest that hsa-miR-320d and hsa-miR-582 may serve as putative biomarkers for AD research.

Risk factors associated with perioperative morbidity and mortality following isolated tricuspid valve replacement.

BACKGROUND: Reports of isolated tricuspid valve replacement (iTVR) are relatively rare. The present study aimed to evaluate independent risk factors of perioperative morbidity and mortality after iTVR. MATERIALS AND METHODS: We retrospectively reviewed 118 consecutive patients (42 males; mean age, 49.1 ± 12.9 y) who underwent iTVR from May 2003 to April 2016 in our center. The multivariate logistic regression model was used to analyze the independent risk factors associated with perioperative morbidity and mortality following iTVR. RESULTS: One hundred one patients (85.6%) were classified as New York Heart Association functional class III or IV preoperatively. The overall perioperative mortality was 11.8% (14/118), and a significant difference was observed between the nonreoperative group and the reoperative group (6.7% versus 18.3%, P = 0.047). The multivariate logistic regression analyses identified that preoperative New York Heart Association functional class IV (OR [odds ratio] = 15.43, 95% CI [confidence interval] = 3.46-68.83, P = 0.000) and ascites (OR = 4.88, 95% CI = 1.24-19.27, P = 0.024) were independent risk factors of perioperative deaths. The previous cardiac surgery (OR = 3.28, 95% CI = 1.41-7.62, P = 0.006) was independently associated with perioperative major adverse events. CONCLUSIONS: The present study revealed that iTVR has relatively high mortality and morbidity rates. Timely surgery may be recommended for this high-risk cohort of patients before the development of severe heart and end-organ failure.