Risk factor and correlation between postoperative serum myoglobin and acute kidney injury after pulmonary endarterectomy.

Background: Acute kidney injury (AKI) is a common and life-threatening complication following pulmonary endarterectomy (PEA). Our study aimed to investigate the risk factors associated with AKI and evaluate the correlation between serum myoglobin (sMb) levels and postoperative AKI. Methods: We conducted a retrospective study involving 134 patients who underwent PEA at China-Japan Friendship Hospital. AKI was defined and staged according to the Kidney Disease Improving Global Outcomes (KDIGO) criteria. Results: During the study period, the incidence of postoperative AKI was 57.5%, and the associated mortality rate was 6.0%. Severe AKI was found to be significantly associated with worse short-term outcomes (P<0.05). Logarithmically transformed postoperative day (POD) 0 sMb levels were significantly associated with AKI [odds ratio (OR) =5.174; 95% confidence interval (CI), 2.307-11.603; P<0.001] and severe AKI (OR =4.605; 95% CI, 1.510-14.048; P=0.007), also had independent predictive value [area under the curve (AUC) =0.776 in AKI and AUC =0.737 in severe AKI]. The optimal cut-off values were 370.544 ng/mL for AKI and 419.473 ng/mL for severe AKI. Furthermore, albumin concentration was found to play a protective role in the development of severe AKI (OR =0.838; 95% CI, 0.716-0.980; P=0.027) when higher than 40.350 g/L. Conclusions: Our findings suggest that a high concentration of POD0 sMb may increase the risk of developing AKI following PEA surgery. Increasing albumin concentration could serve as an effective preventive measure against AKI.

Comparison of pulmonary artery sarcoma and pulmonary thromboembolism according to clinical and computed tomography pulmonary angiography and magnetic resonance imaging characteristics: a single-center retrospective study.

Background: Pulmonary artery sarcoma (PAS) is a very rare malignancy with a poor prognosis; however, its clinical manifestations and imaging findings are often indistinguishable from pulmonary thromboembolism (PTE). We thus aimed to accurately diagnose PAS by comparing the clinical and computed tomography pulmonary angiography (CTPA) and magnetic resonance imaging (MRI) imaging characteristics of PAS and PTE. Methods: This case-control study retrospectively enrolled 20 patients with PAS (from March 2017 to September 2022), 40 patients with central acute PTE, and 40 patients with central chronic PTE (from January 2021 to December 2022) in the China-Japan Friendship Hospital. The following clinical and imaging findings were compared between the three groups: initial symptoms; D-dimer, C-reactive protein, and N-terminal pro B-type natriuretic peptide levels; wall-eclipsing sign (WES); scope of lesion involvement; and morphological characteristics. Signal intensity was also observed on different MRI sequences. Results: The D-dimer level in PAS was significantly lower than that in central acute PTE (P<0.001). The WES was present in 17 cases of PAS (85.0%), which was a greater proportion than that of the central acute PTE and chronic PTE groups (all P values <0.001). The involvement of the pulmonary valve or right ventricular outflow tract was observed in five PAS cases but none of the central acute PTE or chronic PTE cases (all P values =0.001). In 19 PAS cases (95.0%), the lesions grew expansively in the central pulmonary artery. The proximal margin of 18 patients with PAS (90.0%) was bulging or lobulated. Nine cases of PAS (45.0%) showed aneurysm-like dilatation (grape-like sign) of the distal pulmonary artery, representing significantly greater proportion than that of the central acute PTE and chronic PTE groups (all P values <0.001). In 37 patients with central acute PTE (92.5%), the clots were observed to be floating in the pulmonary artery lumen with saddle, tubular or polypoid shape. Eccentric filling defects attached to the pulmonary artery wall were observed in 32 cases of central chronic PTE (80.0%). On MRI, PAS lesions were hyperintense on fat-suppressed T2-weighted imaging and diffusion-weighted imaging, demonstrating heterogeneous enhancement. Conclusions: Comprehensive analysis of the clinical data and imaging features on CTPA and MRI can aid in the accurate differential diagnosis of PAS and PTE.

Hyperlactatemia in patients undergoing pulmonary endarterectomy with deep hypothermic circulatory arrest: Risk factors and its effects on the outcome.

INTRODUCTION: To determine the risk factors of hyperlactatemia in pulmonary endarterectomy (PEA) surgery and assess whether elevated blood lactate levels are associated with adverse outcomes. METHODS: In this retrospective observational study, a total of 111 consecutive patients who underwent PEA for chronic thromboembolic pulmonary hypertension at the XXX Hospital between December 2016 and January 2022 were included. We retrospectively evaluated arterial blood samples analyzed intraoperatively. The pre- and intraoperative risk factors for hyperlactatemia and the postoperative outcomes were recorded. RESULTS: Lactate levels gradually increased during surgery. The optimal cut-off lactate level for major postoperative complications, calculated using receiver operating characteristic analysis, was 7.0 mmol/L. Deep hypothermic circulatory arrest (DHCA) duration, nadir hematocrit, and preoperative pulmonary vascular resistance were risk factors for lactate levels >7 mmol/L. Moreover, the intraoperative peak lactate level during PEA under DHCA was found to be a statistically significant predictor of major complications being associated with longer mechanical ventilation time (r = 0.294; p = .003) and intensive care unit length of stay (r = 0.327; p = .001). CONCLUSIONS: Deep hypothermic circulatory arrest duration, nadir hematocrit, and preoperative pulmonary vascular resistance were associated with hyperlactatemia. Increased lactate levels were independent predictors of longer mechanical ventilation time, intensive care unit length of stay, and major complications.

Circular RNA hsa_circ_0064559 affects tumor cell growth and progression of colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) is the second leading cause of cancer-related deaths globally. It is essential to identify new CRC-associated therapeutic targets and diagnostic biomarkers. Previous studies have demonstrated that a series of circular RNAs (circRNAs) play a crucial role in CRC pathogenesis. This study assessed the potential of hsa_circ_0064559 in tumor cell growth and progression of CRC. METHODS: Six pairs of matched CRC and normal colorectal tissue samples were sequenced using the Affymetrix Clariom D array. Using RNA interference, the expression of thirteen circRNAs was knocked down in CRC cells. The proliferation of CRC cell lines (RKO and SW620 cells) was detected using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay. Apoptosis and cell cycle were determined by flow-cytometric analysis. An in vivo study uses nude mice to establish a CRC mouse model. The differentially expressed genes were analyzed using Affymetrix primeview human GeneChip array and verified by polymerase chain reaction. RESULTS: Affymetrix Clariom D array analysis revealed that thirteen circRNAs were upregulated in CRC. The proliferation of CRC cell lines was decreased, while the proportion of apoptotic and G1 phase cells was higher after hsa_circ_0064559 knockdown. In vivo xenograft nude mice model revealed that the volume and weight of the tumor were reduced by hsa_circ_0064559 knockdown. In Affymetrix primeview human GeneChip array, we found six upregulated genes (STAT1, ATF2, TNFRSF10B, TGFBR2, BAX, and SQSTM1) and two downregulated genes (SLC4A7 and CD274) related to apoptosis and proliferation of colorectal cancer cells after hsa_circ_0064559 knockdown. CONCLUSIONS: The hsa_circ_0064559 knockdown could inhibit the proliferation, promote apoptosis in CRC cell lines in vitro, and inhibit the development of CRC tumors in vivo. The mechanism may be related to activating a wide range of signaling pathways. The hsa_circ_0064559 may be a potential biomarker for early diagnosis or prognosis of CRC and a novel drug target for CRC therapy.

Qualification of Ventricular Flow in Patients With Precapillary Pulmonary Hypertension With 4-dimensional Flow Magnetic Resonance Imaging.

PURPOSE: Our goal was to study both right and left ventricular blood flow in patients with precapillary pulmonary hypertension (pre-PH) with 4-dimensional (4D) flow magnetic resonance imaging (MRI) and to analyze their correlation with cardiac functional metrics on cardiovascular magnetic resonance (CMR) and hemodynamics from right heart catheterization (RHC). MATERIALS AND METHODS: 129 patients (64 females, mean age 47 ± 13 y) including 105 patients with pre-PH (54 females, mean age 49 ± 13 y) and 24 patients without PH (10 females, mean age 40 ± 12 y) were retrospectively included. All patients underwent CMR and RHC within 48 hours. 4D flow MRI was acquired using a 3-dimensional retrospectively electrocardiograph-triggered, navigator-gated phase contrast sequence. Right and left ventricular flow components including the percentages of direct flow (PDF), retained inflow (PRI), delayed ejection flow (PDE), and residual volume (PRVo) were respectively quantified. The ventricular flow components between patients with pre-PH and non-PH were compared and correlations of flow components with CMR functional metrics and hemodynamics measured with RHC were analyzed. Biventricular flow components were compared between survivors and deceased patients during the perioperative period. RESULTS: Right ventricular (RV) PDF and PDE significantly correlated with RVEDV and RV ejection fraction. RV PDF negatively correlated with pulmonary arterial pressure (PAP) and pulmonary vascular resistance. When the RV PDF was <11%, the sensitivity and specificity of RV PDF for predicting mean PAP ≥25 mm Hg were 88.6% and 98.7%, respectively, with an area under the curve value of 0.95 ± 0.02. When RV PRVo was more than 42%, the sensitivity and specificity of RV PRVo for predicting mean PAP ≥25 mm Hg were 85.7% and 98.5%, respectively, with an area under the curve value of 0.95 ± 0.01. Nine patients died during the perioperative period. Biventricular PDF, RV PDE, and PRI of survivors were higher than nonsurvivors whereas RV PRVo increased in deceased patients. CONCLUSIONS: Biventricular flow analysis with 4D flow MRI provides comprehensive information about the severity and cardiac remodeling of PH and may be a predictor of perioperative death of patients with pre-PH.

Right and left ventricular blood pool T2 ratio on cardiac magnetic resonance imaging correlates with hemodynamics in patients with pulmonary hypertension.

OBJECTIVES: Our objective is to compare the right/left ventricular blood pool T1 ratio (RVT1/LVT1), and right/left ventricular blood pool T2 ratio (RVT2/LVT2) on Cardiac Magnetic Resonance Imaging (CMR) between patients with pulmonary hypertension (PH) and normal controls, to analyze the correlation of RVT1/LVT1, RVT2/LVT2 and hemodynamics measured with right heart catheterization (RHC) in patients with PH. METHODS: Forty two patients with PH and 40 gender-and age-matched healthy controls were prospectively included. All patients underwent RHC and CMR within 24 h. The right and left ventricular blood pool T1 and T2 values were respectively measured, and RVT1/LVT1 and RVT2/LVT2 between the PH group and the healthy control were compared. Meanwhile, the correlation between RVT1/LVT1, RV/LVT2 ratio and hemodynamic parameters in patients with PH respectively was analyzed. RESULTS: In the control group, RVT2 was significantly lower than LVT2 (t = 6.782, p < 0.001) while RVT1 also was lower than LVT1 (t = 8.961, p < 0.001). In patients with PH, RVT2 was significantly lower than LVT2 (t = 9.802, p < 0.001) while RVT1 was similar to LVT1 (t = - 1.378, p = 0.176). RVT2/LVT2 in the PH group was significantly lower than that in the control group (p < 0.001). RVT1/LVT1 in PH patients increased in comparison with the control group (p < 0.001). RVT2/LVT2 negatively correlated with pulmonary vascular resistance (r = - 0.506) and positively correlated with cardiac index (r = 0.521), blood oxygen saturation in Superior vena cava, right atrium, right ventricle and pulmonary artery (r = 0.564, 0.603, 0.648, 0.582). CONCLUSIONS: RVT2/LVT2 on T2 mapping could be an additional CMR imaging marker that may assist to evaluate the severity of PH.

Distribution of thrombus predicts severe reperfusion pulmonary edema after pulmonary endarterectomy.

OBJECTIVES: Patients underwent pulmonary endarterectomy (PEA) for chronic thromboembolic pulmonary hypertension (CTEPH). This study aimed to investigate the effect of thrombus distribution on the occurrence of severe reperfusion pulmonary edema (RPE) and identify specific parameters for predicting severe RPE. METHODS: Patients with CTEPH who underwent PEA surgery were retrospectively analyzed. The thrombus in pulmonary arteries were evaluated through computed tomography pulmonary angiography. Based on presence of prolonged artificial ventilation, extracorporeal membrane oxygenation required, or perioperative death due to RPE, the patients were divided into the severe RPE and without severe RPE groups. MAIN RESULTS: Among the 77 patients (29 women), 16 (20.8%) patients developed severe RPE. The right major pulmonary artery (RPA) (0.64[0.58, 0.73] vs 0.58[0.49, 0.64]; p = 0.008) and pulmonary artery trunk (PAT) thrombus ratios (0.48[0.44, 0.61] vs 0.42[0.39, 0.50]; p = 0.009) (the PAT ratio is expressed as the sum of the right middle lobe clot burden and right lower lobe clot burden divided by the total clot burden multiplied by 100) of the severe RPE group was significantly higher than that of the without severe RPE group. Receiver operator characteristics curve identified a PAT ratio of 43.4% as the threshold with areas under the curve = 0.71(95%CI 0.582; 0.841) for the development of severe RPE (sensitivity 0.875, specificity 0.541). The logistic regression analysis demonstrated that age, period from symptom onset to PEA, NT-pro BNP, preoperative mPAP, preoperative PVR, RPA ratio, and PAT ratio were associated with the development of severe RPE. Multivariable logistic regression analysis revealed PAT ratio (odds ratio = 10.2; 95% confidence interval 1.87, 55.53, P = 0.007) and period from symptom onset to PEA (OR = 1.01; 95% CI = 1.00-1.02, P = 0.015) as independent risk factors for the development of severe RPE. CONCLUSIONS: The thrombus distribution could be a key factor in the severity of RPE. PAT ratio and medical history could predict the development of severe RPE.

Preoperative pulmonary vascular resistance and neutrophil-to-lymphocyte ratio predict the demand of extracorporeal membrane oxygenation after pulmonary endarterectomy.

BACKGROUND: Acute respiratory and circulatory collapse might occasionally happen after pulmonary endarterectomy (PEA). We aimed to investigate the utilization of extracorporeal membrane oxygenation (ECMO) after PEA and potential risk factors. METHODS: Demographic characteristics, clinical and surgical data were collected for all patients who underwent PEA from December 2016 to June 2022. All factors were compared between patients in the ECMO group and those in the other group. The most characteristic risk factors were obtained by least absolute shrinkage and selection operator regression and support vector machine machine learning, and receiver operating characteristics (ROC) Curve analysis was performed to verify the diagnostic value of the obtained risk factors. RESULTS: A total of 117 patients underwent PEA, and 8 (6.8%) of them received ECMO treatment intraoperatively or postoperatively. There were significant differences between the two groups in terms of cardiac function, pulmonary vascular resistance (PVR), preoperative inflammation and cardiopulmonary bypass time. The PVR and neutrophil-to-lymphocyte ratio (N/L ratio) were the most characteristic risk factors with an area under the ROC curve of 0.847 (95% confidence interval [CI] = 0.7517-0.9420, p = .005) and 0.896 (95% CI = 0.803-0.989, p = .001), respectively. The ECMO group had higher PVR (1549.4 ± 600.7 vs. 952.9 ± 466.9 dyn.s.cm-5 , p = .004) and N/L ratio (6.3 ± 5.6 vs. 2.4 ± 1.7, p = .001). CONCLUSIONS: PVR and N/L ratio can correctly predict who is likely to receive ECMO treatment after PEA. Therefore, addressing the preoperative inflammatory status might be beneficial but further research is needed.

Clinicopathological Correlation of Chronic Thromboembolic Pulmonary Hypertension: A Retrospective Study.

The pathophysiology of chronic thromboembolic pulmonary hypertension (CTEPH) is largely unknown. Although pulmonary endarterectomy (PEA) is potentially curative, inoperable patients and persistent pulmonary hypertension (PH) following surgery remain a significant problem. In this study, we aim to describe the histopathological characteristics of CTEPH and explore the potential relationship between pulmonary arterial lesions, radiological parameters, and clinical manifestations. Endarterectomized tissues from 81 consecutive patients of CTEPH were carefully collected, sectioned, and examined by experienced pathologists. Pertinent clinical and radiological data were obtained from medical records and operative reports. Neointima, fresh/organized thrombi, recanalized regions, and atherosclerotic lesions were microscopically examined as previously described. Thrombi and atherosclerosis were dominant in UCSD classification level I PEA materials, while recanalized neo-vessels were more frequently observed in UCSD classification level III cases. Degenerative changes of the extracellular matrix were also noticed in the vascular bed. Atherosclerotic lesions were more frequently observed in cases with higher ratio of the pulmonary artery diameter to ascending aorta diameter (PA/AA) reflected by computed tomographic pulmonary arterial scanning. Furthermore, the removal of pulmonary artery complex lesions (with the combination of three to four types of lesions) by PEA was associated with lower postoperative mean pulmonary arterial pressure (mPAP) and decreased incidences of persistent PH. Our study demonstrates that the histopathological features of CTEPH are strongly linked with clinical manifestations and the postoperative outcome after PEA. These data may provide possible evidence for further studies in searching for appropriate causal factors underlying this disease.

Identification of a biomarker and immune infiltration in perivascular adipose tissue of abdominal aortic aneurysm.

Objective: Abdominal aortic aneurysm (AAA) refers to unusual permanent dilation of the abdominal aorta, and gradual AAA expansion can lead to fatal rupture. However, we lack clear understanding of the pathogenesis of this disease. The effect of perivascular adipose tissue (PVAT) on vascular functional status has attracted increasing attention. Here, we try to identify the potential mechanisms linking AAA and PVAT. Methods: We downloaded dataset GSE119717, including 30 dilated AAA PVAT samples and 30 non-dilated aorta PVAT samples from AAA cases, from Gene Expression Omnibus to identify differentially expressed genes (DEGs). We performed pathway enrichment analysis by Metascape, ClueGo and DAVID to annotate PVAT functional status according to the DEGs. A protein-protein interaction network, the support vector machine (SVM)-recursive feature elimination and the least absolute shrinkage and selection operator regression model were constructed to identify feature genes. Immune infiltration analysis was explored by CIBERSORT. And the correlation between feature gene and immune cells was also calculated. Finally, we used the angiotensin II (Ang II)-ApoE-/- mouse model of AAA to verify the effect of feature gene expression by confirming protein expression using immunohistochemistry and western blot. Results: We identified 22 DEGs, including 21 upregulated genes and 1 downregulated gene. The DEGs were mainly enriched in neutrophil chemotaxis and IL-17 signaling pathway. FOS was identified as a good diagnostic feature gene (AUC = 0.964). Immune infiltration analysis showed a higher level of T cells follicular helper, activated NK cells, Monocytes, activated Mast cells in AAA group. And FOS was correlated with immune cells. Immunohistochemistry and western blot confirmed higher FOS expression in PVAT of the AAA mouse model compared to control group. Conclusion: The differentially expressed genes and pathways identified in this study provide further understanding of how PVAT affects AAA development. FOS was identified as the diagnostic gene. There was an obvious difference in immune cells infiltration between normal and AAA groups.

The alterations in molecular markers and signaling pathways in chronic thromboembolic pulmonary hypertension, a study with transcriptome sequencing and bioinformatic analysis.

Background: At present, the alterations in molecular markers and signaling pathways in chronic thromboembolic pulmonary hypertension (CTEPH) remain unclear. We aimed to compare the difference of molecular markers and signaling pathways in patients with CTEPH and healthy people with transcriptome sequencing and bioinformatic analysis. Methods: We prospectively included 26 patients with CTEPH and 35 sex- and age-matched healthy volunteers as control. We extracted RNA from whole blood samples to construct the library. Then, qualified libraries were sequenced using PE100 strategy on BGIseq platform. Subsequently, the DESeq2 package in R was used to screen differentially expressed mRNAs (DEmRNAs) and differentially expressed long non-coding RNAs (DElncRNAs) of 7 patients with CTEPH and 5 healthy volunteers. Afterwards, we performed functional enrichment and protein-protein interaction analysis of DEmRNAs. We also performed lncRNA-mRNA co-expression analysis and lncRNA-miRNA-mRNA network construction. In addition, we performed diagnostic analysis on the GSE130391 dataset. Finally, we performed reverse transcription polymerase chain reaction (RT-PCR) of genes in 19 patients with CTEPH and 30 healthy volunteers. Results: Gender and age between patients with CTEPH and healthy controls, between sequencing group and in vitro validation group, were comparable. A total of 437 DEmRNAs and 192 DElncRNAs were obtained. Subsequently, 205 pairs of interacting DEmRNAs and 232 pairs of lncRNA-mRNA relationship were obtained. DEmRNAs were significantly enriched in chemokine signaling pathway, metabolic pathways, arachidonic acid metabolism, and MAPK signaling pathway. Only one regulation pathway of SOBP-hsa-miR-320b-LINC00472 was found through ceRNA network construction. In diagnostic analysis, the area under curve (AUC) values of LINC00472, PIK3R6, SCN3A, and TCL6, respectively, were 0.964, 0.893, 0.750, and 0.732. Conclusion: The identification of alterations in molecules and pathways may provide further research directions on pathogenesis of CTEPH. Additionally, LINC00472, PIK3R6, SCN3A, and TCL6 may act as the potential gene markers in CTEPH.

Characteristics of Right Ventricular Blood Flow in Patients With Chronic Thromboembolic Pulmonary Hypertension: An Analysis With 4-Dimensional Flow Cardiovascular Magnetic Resonance Imaging.

Background: Blood flow is closely related to function, but currently, the relationship of right ventricular (RV) blood flow components with RV function and hemodynamics in patients with chronic thromboembolic pulmonary hypertension (CTEPH) remains unclear. Our objective is to qualify RV function with 4-dimensional flow cardiovascular magnetic resonance (4D-Flow CMR) imaging and to investigate the correlation between RV flow and hemodynamics in patients with CTEPH. Methods: Retrospective enrollment included 67 patients with CTEPH (mean age 47.8±14.2 years, 47 men) who underwent CMR and right heart catheterization (RHC) within 2 days. RHC was used to evaluate hemodynamics. RV flow components including the percentages of direct flow (PDF), retained inflow (PRI), delayed ejection flow (PDEF), and residual volume (PRVo) were quantified on 4D-Flow sequence. RV functional metrics were determined with the CINE balanced steady-state free precession sequence. The sum of PDF and PDEF was compared with RV eject fraction (RVEF). The correlation among RV flow components, RV functional metrics and hemodynamics was analyzed with spearman correlation analysis. Results: The median (interquartile range) of RVEF, PDF, PDEF, PRI, and PRVo, respectively was 35.5% (18.2, 45.6%), 18% (8.4, 21.4%), 15.1% (13.5, 19.0%), 15.9% (13.8, 20.8%), and 50.6% (35.6, 60.4%). The sum of PDF and PDEF is 35.1% (24.8, 46.6%), which was similar to RVEF (z = 0.58, p = 0.561). PDF negatively correlated with right ventricular end-systolic volume index (RVESVI), right ventricular myocardial mass index (RVMI) and right ventricular global longitudinal strain (r = -0.61, -0.65, -0.64, p < 0.001). PRVo positively correlated with RVESVI and RVMI (r = 0.50, 0.58, p < 0.001). PDF negatively correlated with pulmonary vascular resistance (PVR) (r = -0.72, p < 0.001) while it positively correlated with cardiac output (CO) and cardiac index (CI) (r = 0.64 & 0.52, p < 0.001). PRVo positively correlated with mean pulmonary pressure and PVR (r = 0.57&0.54, p < 0.001). Total five patients died in the perioperative period. RVEF in the deceased patients was similar to survivors (z = -1.163, p = 0.092). In comparison with the survivors, RVPDF in the deceased patients significantly reduced (z = -2.158, p = 0.029) while RVPDEF, RVPRI, and RVPRVo in deceased patients were similar to survivors. Conclusion: 4D-Flow CMR can provide simultaneous quantification of RV function and hemodynamics in the assessment of CTEPH without breath-holding. The reduced PDF and increased PRVo were the main characteristics of RV flow in CTEPH.

Case Report: Successful Concomitant Pulmonary Thromboendarterectomy and Carotid Endarterectomy.

Pulmonary thromboendarterectomy is the treatment of choice for chronic thromboembolic pulmonary hypertension. Pulmonary thromboendarterectomy concomitant with additional cardiac procedures was reported as safe and feasible. However, the treatment strategy for chronic thromboembolic pulmonary hypertension patients with severe carotid stenosis is still not clear. We describe a case of successful concomitant pulmonary thromboendarterectomy and carotid endarterectomy.

Duration of regional cerebral oxygen saturation under 40% is a risk factor for neurological injury following pulmonary thromboendarterectomy: A prospective observational study.

BACKGROUND: Deep hypothermic circulatory arrest (DHCA) is nowadays commonly used in pulmonary thromboendarterectomy (PTE). Neurological injury related to DHCA severely impairs the prognosis of patients. However, the risk factors and predictors of neurological injury are still unclear. METHODS: We conducted a prospective observational study, including 82 patients diagnosed as chronic thromboembolic pulmonary hypertension and underwent PTE alone in our center from December 2016 to May 2021. Demographic characteristics, clinical and surgical data, and neurological adverse events were recorded prospectively. Univariate and multivariate analyses were conducted to identify the predictors of neurological injury. RESULTS: Eleven (13.4%) patients exhibited neurological injuries after surgery. Univariate analysis showed that the duration of regional cerebral oxygen saturation (rSO2 ) under 40% (p < .001), the minimum rSO2 (p = .006), and the percentage of decrease in rSO2 (p = .011) were significantly associated with neurological injury. Multivariate analysis showed that the duration of rSO2 under 40% was an independent predictor for postoperative neurological injury (odds ratio = 3.896, 95% confidence interval: 1.812-8.377, p < .001). The receiver operating characteristic curve showed that when the cut-off value was 1.25 min, its sensitivity for predicting neurological injury was 63.6% with a specificity of 88.7%. CONCLUSIONS: The duration of rSO2 under 40% is an independent predictor for neurological injury following PTE. For complicated lesions, more times of circulatory arrest were much safer and more reliable than a prolonged time of a single circulatory arrest. The circulation should be restored as soon as possible, when the rSO2 under 40% is detected, rather than waiting for 5 min.

Resting heart rate as a preoperative predictor of postoperative atrial fibrillation after pulmonary thromboendarterectomy.

BACKGROUND: As a marker of the autonomic nervous system, resting heart rate is a predictor of postoperative atrial fibrillation (POAF). However, its predictive value for POAF after pulmonary thromboendarterectomy (PTE) has not been adequately studied. METHODS: We enrolled 97 patients who underwent PTE in our hospital from December 2016 to November 2021 in this retrospective study. Almost all preoperative characteristics, including electrocardiogram, demographics, hematologic and biochemical indices, echocardiography, and pulmonary hemodynamics, were compared between patients with and without POAF. Multivariate logistic regression analysis was used to identify the independent risk factors for POAF after PTE. RESULTS: Overall, 21 patients (21.6%) suffered from POAF after PTE. Compared with patients without POAF, those with POAF were older (p = .049), with a higher resting heart rate (p = .012), and higher platelet count (p = .040). In the binary logistic regression analysis, the resting heart rate (odds ratio [OR] = 1.043, 95% confidence interval [CI] = 1.009-1.078, p = .012) and age (OR = 1.051, 95% CI = 1.003-1.102, p = .037) were independent risk factors for POAF after PTE. The optimal cutoff point of resting heart rate was 89.5 with sensitivity and specificity of 47.6% and 77.6%. When the cutoff value of the age was 54.5, its sensitivity for predicting POAF was 71.4%, with a specificity of 59.2%. CONCLUSIONS: POAF is common after PTE surgery, and the incidence may be underestimated. The resting heart rate and age are independent preoperative risk factors for POAF after PTE. Considering the lower predictive power of the resting heart and age, further large-scale studies are needed.

Right ventricular end-systolic remodeling index on cardiac magnetic resonance imaging: comparison with other functional markers in patients with chronic thromboembolic pulmonary hypertension.

BACKGROUND: Cardiac magnetic resonance imaging (CMR) can provide important metrics of pulmonary hypertension. In the current study, we investigated whether the CMR-derived right ventricular end-systolic remodeling index (RVESRI) could be a metric in assessing the function and hemodynamics of chronic thromboembolic pulmonary hypertension (CTEPH). METHODS: A total of 64 patients (45±14 years, 37 males), including 46 patients with CTEPH and 18 patients with chronic pulmonary thromboembolism (CTE), were retrospectively enrolled. All patients underwent right heart catheterization and CMR within 7 days. RVESRI, right ventricular eccentricity index, right ventricular end-diastolic and end-systolic volume index, right ventricular ejection fraction, right ventricular cardiac output, and strain were analyzed on cine images of CMR. Hemodynamic parameters including mean pulmonary arterial pressure, pulmonary vascular resistance, and cardiac output were obtained from right heart catheterization. RESULTS: RVESRI of all patients was 1.50 (IQR, 1.26-1.90). Compared with CTE patients, RVESRI in patients with CTEPH was significantly increased (U=27.5, P<0.001). The interclass correlation coefficients of intra-observer reproducibility and inter-observer reproducibility for RVESRI measurement were 0.96 (95% CI, 0.93-0.97) and 0.99 (95% CI, 0.98-0.99), respectively. RVESRI positively correlated with right ventricular end-diastolic and end-systolic volume index and right ventricular global longitudinal strain (r=0.79, 0.83, 0.62, P<0.001), while it was negatively correlated with right ventricular ejection fraction (r=-0.64, P<0.001), right ventricular cardiac output (r=-0.50, P<0.001), and right ventricular eccentricity index (r=-0.81, P<0.001). RVESRI had a positive correlation with mean pulmonary arterial pressure (r=0.65, P<0.001) and pulmonary vascular resistance (r=0.69, P<0.001), while it was negatively correlated with cardiac output (r=-0.64, P<0.001). The receiver operating characteristic curve indicated that RVESRI >1.35 had a sensitivity of 97.8% and specificity of 83.3% in predicting mean pulmonary arterial pressure ≥25 mmHg, and its area under the curve (AUC) was 0.96±0.02. Meanwhile, the AUC of RVESRI was similar to RVEI (Z=1.635, P=0.102) and was more than the diameter of the main pulmonary artery (MPA) (Z=2.26, P=0.02) and the ratio of the MPA and ascending aorta diameter (MPA/AAo) (Z=3.826, P<0.001) in predicting mean pulmonary arterial pressure ≥25 mmHg. CONCLUSIONS: RVESRI measured on CMR is a simple and reproducible metric in assessing right ventricular function and hemodynamics in CTEPH patients.

WNT5B promotes vascular smooth muscle cell dedifferentiation via mitochondrial dynamics regulation in chronic thromboembolic pulmonary hypertension.

Chronic thromboembolic pulmonary hypertension (CTEPH) is characterized by proliferative vascular remodeling. Abnormal vascular smooth muscle cell (VSMC) phenotype switching is crucial to this process, highlighting the need for VSMC metabolic changes to cover cellular energy demand in CTEPH. We report that elevated Wnt family member 5B (WNT5B) expression is associated with vascular remodeling and promotes VSMC phenotype switching via mitochondrial dynamics regulation in CTEPH. Using primary culture of pulmonary artery smooth muscle cells, we show that high WNT5B expression activates VSMC proliferation and migration and results in mitochondrial fission via noncanonical Wnt signaling in CTEPH. Abnormal VSMC proliferation and migration were abolished by mitochondrial division inhibitor 1, an inhibitor of mitochondrial fission. Secreted frizzled-related protein 2, a soluble scavenger of Wnt signaling, attenuates VSMC proliferation and migration by accelerating mitochondrial fusion. These findings indicate that WNT5B is an essential regulator of mitochondrial dynamics, contributing to VSMC phenotype switching in CTEPH.

Efficacy, Safety, and Cost-Effectiveness of Intracavitary Electrocardiography-Guided Catheter Tip Placement for Totally Implantable Venous Access Port.

OBJECTIVE: Intracavitary electrocardiography (IC-ECG) has been extensively used for locating the catheter tip of the central venous access devices (CVADs) with favorable safety and accuracy. We aimed to evaluate the efficacy, safety, and cost-effectiveness of IC-ECG-guided catheter tip placement for totally implantable venous access port (TIVAP) by comparing with the standard fluoroscopy method. METHODS: A total of 231 patients who underwent TIVAP implantation from September 2019 to April 2021 were enrolled in the retrospective study. Fluoroscopy and IC-ECG were conducted intraoperatively to confirm the position of catheter tips. Demographic characteristics, surgical data, the catheter tip position, complication rate, and incidence, cost of procedures, and indwelling time were compared between the two groups. Univariate and multivariate analyses were used to identify the risk factors of TIVAP-related complications. RESULTS: There was no significance between the fluoroscopy group and the IC-ECG group in terms of the rate of ideal position (P = 0.733). Nine patients (3.9%) developed TIVAP-related complications. Complication rates and incidence were similar in the fluoroscopy group and the IC-ECG group (3.1% and 0.114/1000 catheter days vs. 4.4% and 0.105/1000 catheter days). The Kaplan-Meier curve showed that there was no significant difference in indwelling time between the 2 groups (Log Rank P = 0.634). Binary logistic regression analysis showed that body mass index (BMI) was an independent risk factor for TIVAP-related complications (OR = 1.334, 95%CI: 1.139 - 1.563, P < 0.001). The IC-ECG group was less costly than the fluoroscopy group (¥9928 ± 362 vs. ¥11762 ± 431, P < 0.001). CONCLUSIONS: IC-ECG-guided catheter tip placement for TIVAP is feasible, safe, and cost-effective, with high accuracy, low risk of complications, and lower cost. It may be considered as an alternative to the standard fluoroscopy method for catheter tip placement of TIVAP.

Radiomics signature of epicardial adipose tissue for predicting postoperative atrial fibrillation after pulmonary endarterectomy.

Purpose: This study aimed to construct a radiomics signature of epicardial adipose tissue for predicting postoperative atrial fibrillation (POAF) after pulmonary endarterectomy (PEA) in patients with chronic thromboembolic pulmonary hypertension (CTEPH). Methods: We reviewed the preoperative computed tomography pulmonary angiography images of CTEPH patients who underwent PEA at our institution between December 2016 and May 2022. Patients were divided into training/validation and testing cohorts by stratified random sampling in a ratio of 7:3. Radiomics features were selected by using intra- and inter-class correlation coefficient, redundancy analysis, and Least Absolute Shrinkage and Selection Operator algorithm to construct the radiomics signature. The area under the receiver operating characteristic curve (AUC), calibration curve, and decision curve analysis (DCA) were used to evaluate the discrimination, calibration, and clinical practicability of the radiomics signature. Two hundred-times stratified five-fold cross-validation was applied to assess the reliability and robustness of the radiomics signature. Results: A total of 93 patients with CTEPH were included in this study, including 23 patients with POAF and 70 patients without POAF. Five of the 1,218 radiomics features were finally selected to construct the radiomics signature. The radiomics signature showed good discrimination with an AUC of 0.804 (95%CI: 0.664-0.943) in the training/validation cohort and 0.728 (95% CI: 0.503-0.953) in the testing cohorts. The average AUC of 200 times stratified five-fold cross-validation was 0.804 (95%CI: 0.801-0.806) and 0.807 (95%CI: 0.798-0.816) in the training and validation cohorts, respectively. The calibration curve showed good agreement between the predicted and actual observations. Based on the DCA, the radiomics signature was found to be clinically significant and useful. Conclusion: The radiomics signature achieved good discrimination, calibration, and clinical practicability. As a potential imaging biomarker, the radiomics signature of epicardial adipose tissue (EAT) may provide a reference for the risk assessment and individualized treatment of CTEPH patients at high risk of developing POAF after PEA.

Identification of a Novel Gene Correlated With Vascular Smooth Muscle Cells Proliferation and Migration in Chronic Thromboembolic Pulmonary Hypertension.

Objective: Chronic thromboembolic pulmonary hypertension (CTEPH) is characterized by thrombofibrotic obstruction of the proximal pulmonary arteries, which result in vascular remodeling of the distal pulmonary artery. While the cellular and molecular mechanisms underlying CTEPH pathogenesis remain incompletely understood, recent evidence implicates vascular remodeling. Here, we identify the molecular mechanisms that contribute to vascular remodeling in CTEPH. Methods: Microarray data (GSE130391) for patients with CTEPH and healthy controls were downloaded from the Gene Expression Omnibus (GEO) and screened for differentially expressed genes (DEGs). DEGs were functionally annotated using Gene Ontology (GO) functional analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. A protein-protein interaction (PPI) network was constructed to identify hub genes. Finally, pulmonary artery samples were harvested from patients with CTEPH (n = 10) and from controls (n = 10) and primary vascular smooth muscle cells (VSMCs) were cultured. Effects of the proto-oncogene FOS on VSMC proliferation and migration were assessed using expression and knockdown studies. Results: We detected a total of 292 DEGs, including 151 upregulated and 141 downregulated genes. GO analysis revealed enrichment of DEGs in biological processes of signal transduction, response to lipopolysaccharide, signal transduction, and myeloid dendritic cell differentiation. Molecular function analysis revealed enrichment in tumor necrosis factor (TNF)-activated receptor activity, transcriptional activator activity, and protein homodimerization activity. The expression of TNF-α and its receptor (sTNFR1 and sTNFR2) were significantly higher in CTEPH group, compared with control group. KEGG pathway analysis revealed enrichment in salmonella infection, pathways in cancer, osteoclast differentiation, and cytokine-cytokine receptor interaction. Hub genes in the PPI included FOS, suggesting an important role for this gene in vascular remodeling in CTEPH. Primary VSMCs derived from patients with CTEPH showed increased FOS expression and high proliferation and migration, which was attenuated by FOS inhibition. In control VSMCs, TNF-α treatment increased proliferation and migration, which FOS inhibition likewise attenuated. Conclusion: TNF-α drives CTEPH pathogenesis by promoting VSMC proliferation and migration via increased FOS expression. These results advance our understanding of the molecular mechanisms of vascular remodeling in CTEPH, and may inform the development of new therapeutic targets.