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Cardiology in the Young Jul 2023Tricuspid atresia with common arterial trunk is a very rare association in complex CHD. This association has even more infrequently been documented concomitantly with...
Tricuspid atresia with common arterial trunk is a very rare association in complex CHD. This association has even more infrequently been documented concomitantly with interrupted aortic arch. We present the diagnosis and initial surgical management of an infant with a fetal diagnosis of tricuspid atresia and common arterial trunk, with additional postnatal finding of interrupted aortic arch with interruption between the left common carotid and left subclavian artery. Due to the infant's small size, she was initially palliated with bilateral pulmonary artery bands and a ductal stent. This was followed by septation of the common arterial trunk and interrupted aortic arch repair and 4 mm right subclavian artery to main pulmonary artery shunt placement at two months of age. She was discharged home on day of life 81.
Topics: Infant; Female; Humans; Tricuspid Atresia; Truncus Arteriosus, Persistent; Pulmonary Artery; Aorta, Thoracic
PubMed: 36472122
DOI: 10.1017/S1047951122003602 -
Arteriosclerosis, Thrombosis, and... Jul 2023Circular RNAs (circRNAs) have been implicated in pulmonary hypertension progression through largely unknown mechanisms. Pulmonary artery endothelial cell (PAEC)...
BACKGROUND
Circular RNAs (circRNAs) have been implicated in pulmonary hypertension progression through largely unknown mechanisms. Pulmonary artery endothelial cell (PAEC) dysfunction is a hallmark in the pathogenesis of pulmonary hypertension. However, the specific role of circular RNAs in PAEC injury caused by hypoxia remains unclear.
METHODS
In this study, using the Western blotting, RNA pull down, Dual-luciferase reporter assay, immunohistochemistry, and immunofluorescence, we identified a novel circular RNA derived from alternative splicing of the keratin 4 gene (circKrt4).
RESULTS
CircKrt4 was upregulated in lung tissues and plasma and specifically in PAECs under hypoxic conditions. In the nucleus, circKrt4 induces endothelial-to-mesenchymal transition by interacting with the Pura (transcriptional activator protein Pur-alpha) to promote N-cadherin gene activation. In the cytoplasm, increased circKrt4 leads to mitochondrial dysfunction by inhibiting cytoplasmic-mitochondrial shuttling of mitochondrial-bound Glpk (glycerol kinase). Intriguingly, circKrt4 was identified as a super enhancer-associated circular RNA that is transcriptionally activated by a transcription factor, CEBPA (CCAAT enhancer binding protein alpha). Furthermore, RBM25 (RNA-binding-motif protein 25) was found to regulate circKrt4 cyclization by increase the back-splicing of gene.
CONCLUSIONS
These findings demonstrate that a super enhancer-associated circular RNA-circKrt4 modulates PAEC injury to promote pulmonary hypertension by targeting Pura and Glpk.
Topics: Mice; Animals; Pulmonary Artery; RNA, Circular; Hypertension, Pulmonary; Cell Proliferation; Hypoxia; RNA; Endothelial Cells
PubMed: 37139839
DOI: 10.1161/ATVBAHA.122.318842 -
Journal of the American College of... Aug 2023Neonates with symptomatic tetralogy of Fallot (sTOF) with hypoplastic pulmonary arteries (hPA) are considered high risk. Data are needed to inform the impact of hPA on...
BACKGROUND
Neonates with symptomatic tetralogy of Fallot (sTOF) with hypoplastic pulmonary arteries (hPA) are considered high risk. Data are needed to inform the impact of hPA on outcomes, and the ideal management strategy.
OBJECTIVES
The objectives of this study were to quantify the impact of hPA on outcomes in neonates with sTOF and measure the impact of strategy on pulmonary artery (PA) growth in this population.
METHODS
Neonates with sTOF from 2005 to 2017 were reviewed from the Congenital Cardiac Research Collaborative. Criteria for hPA included a unilateral PA z score <-2.0 and contralateral PA z score <0. Primary outcome was mortality. Secondary outcomes included reintervention and PA growth.
RESULTS
We included 542 neonates with sTOF, including 188 (35%) with hPA and 354 (65%) with normal PA, with median follow-up of 4.1 years. Median right and left hPA z scores were -2.19 (25th-75th percentile: -2.55 to -1.94) and -2.23 (25th-75th percentile: -2.64 to -1.91), respectively. Staged repair (vs primary TOF repair) was less common in the hPA cohort (36 vs 44%; P = 0.07). Survival was similar between groups (unadjusted P = 0.16; adjusted P = 0.25). Reintervention was more common in the hPA group (HR: 1.28; 95% CI: 1.01-1.63; P = 0.044); there was no difference after definitive repair (HR: 1.21; 95% CI: 0.93-1.58; P = 0.16). PA growth at 1 year was greater in the hPA cohort, particularly for the right PA (P < 0.001).
CONCLUSIONS
Despite perception, the presence of hPA in neonates with sTOF conferred no increase in overall hazard of mortality or reintervention after definitive repair. PA growth was superior in the hPA cohort. These findings suggest that the presence of hPA does not adversely impact outcomes in sTOF.
Topics: Infant, Newborn; Humans; Infant; Tetralogy of Fallot; Pulmonary Artery; Treatment Outcome; Retrospective Studies
PubMed: 37558375
DOI: 10.1016/j.jacc.2023.05.051 -
Pediatric Cardiology Oct 2023This study aimed to identify the influence of the non-confluent pulmonary artery originating from the bilateral arterial ducts (AD) on the outcomes of the Fontan...
This study aimed to identify the influence of the non-confluent pulmonary artery originating from the bilateral arterial ducts (AD) on the outcomes of the Fontan circulation. We retrospectively reviewed the records of nine patients with bilateral AD and a non-confluent pulmonary artery in a single ventricle at our institution between 1993 and 2023. Three patients showed maintained AD or underwent a systemic-pulmonary shunt for stenotic AD, followed by the Glenn procedure. Four patients underwent systemic-pulmonary shunt with angioplasty as the first palliation, followed by the Glenn procedure. Two patients underwent systemic-pulmonary shunt or AD stenting as the first palliation and systemic-pulmonary shunt with angioplasty as the second palliation. There were no cases of interstage mortality. Pulmonary arteries grew and achieved a good balance (pre-Fontan pulmonary artery index [PAI], 164 ± 27 mm/m; right/left PAI ratio, 1.06 ± 0.23). All patients underwent the Fontan procedure (median, 3.5 years; range, 2.3-6.4 years) and were followed up for 7.8 years (range, 0.1-16.4 years) after the procedure. One patient required hospitalization for heart failure at 1.8 years, and three patients required catheter intervention for pulmonary stenosis within 2 months after the Fontan procedure. Non-confluent pulmonary arteries originating from the bilateral AD do not preclude Fontan completion and good Fontan outcomes by restoring balance to pulmonary blood flow. Due to the limited sample size in this study, additional research is imperative to delve deeper into our findings and enhance understanding of the most effective surgical approach for this disease.
Topics: Child; Child, Preschool; Humans; Ductus Arteriosus, Patent; Fontan Procedure; Pulmonary Artery; Retrospective Studies; Treatment Outcome
PubMed: 37453931
DOI: 10.1007/s00246-023-03230-w -
Medicine Feb 2024Pulmonary artery sarcoma (PAS) is a rare malignant tumor primarily originating from the pulmonary artery's intima or subintima. Approximately one-third of cases are...
RATIONALE
Pulmonary artery sarcoma (PAS) is a rare malignant tumor primarily originating from the pulmonary artery's intima or subintima. Approximately one-third of cases are classified as undifferentiated type. Its clinical manifestations lack specificity, dyspnea is the main symptom but can also present with chest pain, cough, hemoptysis, and other discomforts, making it prone to misdiagnosis as pulmonary embolism (PE).
PATIENT CONCERNS
A 50-year-old woman was admitted to the hospital with "dyspnea for more than 3 months, aggravated for 2 days," and computed tomography pulmonary angiography suggesting "bilateral multiple pulmonary embolisms."
DIAGNOSES
The patient was initially misdiagnosed as PE, and was later definitively diagnosed as undifferentiated pleomorphic sarcoma of the pulmonary artery by pathologic biopsy.
INTERVENTIONS AND OUTCOMES
The patient was initially treated with anticoagulant therapy, but her dyspnea was not relieved. After that, she underwent positron emission computed tomography (PET-CT) and other investigations, which suggested the possibility of PAS, and then she underwent pulmonary endarterectomy to remove the lesion, which relieved her symptoms and was advised to seek further medical attention from the Department of Oncology and Department of Radiotherapy.
LESSONS
PAS can be easily misdiagnosed as PE. If a diagnosis of PE is made, but anticoagulation or even thrombolytic therapy proves ineffective, and there is no presence of PE causative factors such as deep vein thrombosis in the lower extremities, or D-dimer levels are not high, one should be cautious and consider the possibility of PAS.
Topics: Humans; Female; Middle Aged; Pulmonary Artery; Positron Emission Tomography Computed Tomography; Hypertension, Pulmonary; Pulmonary Embolism; Lung Neoplasms; Soft Tissue Neoplasms; Dyspnea; Sarcoma
PubMed: 38394547
DOI: 10.1097/MD.0000000000037194 -
The Journal of Heart and Lung... Jul 2024In patients with end-stage chronic obstructive pulmonary disease (COPD), severe pulmonary hypertension (PH) is frequently associated with less severe airway obstruction...
BACKGROUND
In patients with end-stage chronic obstructive pulmonary disease (COPD), severe pulmonary hypertension (PH) is frequently associated with less severe airway obstruction as compared to mild or no PH. However, the histologic correlate of this finding is not clear. We aimed to quantify remodeling of pulmonary arteries, airways, and parenchyma in random samples of explanted end-stage COPD lungs.
METHODS
We quantified remodeling of small pulmonary arteries, small airways, and the degree of emphysema (mean interseptal distance [MID]) with dedicated software. As primary objective, we compared COPD patients with severe PH (SevPH-COPD) with age- and sex-matched MildPH-COPD. For comparison, we also investigated COPD lungs with no PH (NoPH-COPD), idiopathic PAH (IPAH), and healthy donors.
RESULTS
We included n = 17 SevPH-COPD (mPAP = 43 [39-45]mm Hg), n = 17 MildPH-COPD (mPAP = 28 [24-31]mm Hg), n = 5 NoPH-COPD (mPAP = 18 [16-19]mm Hg), n = 10 IPAH (mPAP = 72 [65-91]mm Hg), and n = 10 healthy donor lungs. SevPH-COPD versus MildPH-COPD was characterized by better preserved forced vital capacity (51% vs 40% predicted, p < 0.05), less emphysema (MID 169 µm vs 279 µm, p < 0.001), and less PAS-positive and CD45-positive mucosa cells (15% vs 22%, p = 0.063% and 5% vs 7%, p = 0.058) suggesting less airway inflammation. In COPD patients, intimal and medial thickening were strongly correlated with mPAP (r = 0.676, p < 0.001 and r = 0.595, p < 0.001). MID was negatively correlated with mPAP (r = -0.556, p < 0.001) and was highest in NoPH-COPD (mean 281 µm), suggesting that emphysema per se is not associated with PH.
CONCLUSIONS
End-stage COPD with severe PH is characterized by pronounced pulmonary vascular remodeling, less inflammation of small airways, and less emphysema as compared to COPD with mild PH or no PH, suggesting that COPD with severe PH may represent a unique phenotype of COPD.
Topics: Humans; Pulmonary Disease, Chronic Obstructive; Male; Female; Hypertension, Pulmonary; Middle Aged; Vascular Remodeling; Severity of Illness Index; Aged; Pulmonary Artery; Airway Remodeling; Lung; Retrospective Studies
PubMed: 38382583
DOI: 10.1016/j.healun.2024.02.1044 -
Journal of Magnetic Resonance Imaging :... Jul 2024
Editorial for "Assessment of Pulmonary Arteries Hemodynamics and Its Relationship With Cardiac Remodeling and Myocardial Fibrosis in Athletes With Four-Dimensional Flow MRI".
Topics: Humans; Pulmonary Artery; Ventricular Remodeling; Fibrosis; Athletes; Hemodynamics; Myocardium; Magnetic Resonance Imaging
PubMed: 37830255
DOI: 10.1002/jmri.29066 -
Current Problems in Cardiology Aug 2023Right ventricular-pulmonary arterial (RV-PA) coupling is an important determinant in the development of right ventricular dilatation. RV-PA coupling is defined as the... (Review)
Review
Right ventricular-pulmonary arterial (RV-PA) coupling is an important determinant in the development of right ventricular dilatation. RV-PA coupling is defined as the ratio of pulmonary arterial elastance (an index of arterial load) and right ventricular end-systolic elastance (an index of contractility). A retrospective study of postoperative 135 TOF patients who underwent for pulmonary valve replacement was conducted. RV-PA coupling was calculated noninvasively using Ea/Emax (cardiac magnetic resonance) = ventricular end-systolic volume/ventricular systolic volume, equation and patients were divided into coupling and uncoupling group and compared the results on the basis of echocardiography and cardiopulmonary exercise test. Lower tricuspid annular plane systolic excursion, percentage predictive peak VO, VE/VCO at anaerobic threshold, (AT), VE/VCO at peak, Minute ventilation, (VE) Volume of Carbondioxide output, (VCO) slope, volume of oxygen output (VO) work rate (WR) slope, and WR at VO peak were identified as risk factors for uncoupling of RV-PA. In RV-PA coupling combination of echocardiography and cardiopulmonary exercise test revealed the most important modality to identify risk factor and may be useful for therapeutic decision making by identifying patients of especially high risk for inadequate therapy.
Topics: Humans; Heart Ventricles; Pulmonary Artery; Exercise Test; Retrospective Studies; Hypertension, Pulmonary; Echocardiography; Stroke Volume; Ventricular Dysfunction, Right
PubMed: 35460685
DOI: 10.1016/j.cpcardiol.2022.101214 -
Biomedicine & Pharmacotherapy =... May 2024Pulmonary hypertension (PH) is characterised by an increase in pulmonary arterial pressure, ultimately leading to right ventricular failure and death. We have previously...
AIMS
Pulmonary hypertension (PH) is characterised by an increase in pulmonary arterial pressure, ultimately leading to right ventricular failure and death. We have previously shown that nerve growth factor (NGF) plays a critical role in PH. Our objectives here were to determine whether NGF controls Connexin-43 (Cx43) expression and function in the pulmonary arterial smooth muscle, and whether this mechanism contributes to NGF-induced pulmonary artery hyperreactivity.
METHODS AND RESULTS
NGF activates its TrkA receptor to increase Cx43 expression, phosphorylation, and localization at the plasma membrane in human pulmonary arterial smooth muscle cells, thus leading to enhanced activity of Cx43-dependent GAP junctions as shown by Lucifer Yellow dye assay transfer and fluorescence recovery after photobleaching -FRAP- experiments. Using both in vitro pharmacological and in vivo SiRNA approaches, we demonstrate that NGF-dependent increase in Cx43 expression and activity in the rat pulmonary circulation causes pulmonary artery hyperreactivity. We also show that, in a rat model of PH induced by chronic hypoxia, in vivo blockade of NGF or of its TrkA receptor significantly reduces Cx43 increased pulmonary arterial expression induced by chronic hypoxia and displays preventive effects on pulmonary arterial pressure increase and right heart hypertrophy.
CONCLUSIONS
Modulation of Cx43 by NGF in pulmonary arterial smooth muscle cells contributes to NGF-induced alterations of pulmonary artery reactivity. Since NGF and its TrkA receptor play a role in vivo in Cx43 increased expression in PH induced by chronic hypoxia, these NGF/Cx43-dependent mechanisms may therefore play a significant role in human PH pathophysiology.
Topics: Animals; Humans; Male; Rats; Cells, Cultured; Connexin 43; Gap Junctions; Hypertension, Pulmonary; Muscle, Smooth, Vascular; Myocytes, Smooth Muscle; Nerve Growth Factor; Phosphorylation; Pulmonary Artery; Rats, Sprague-Dawley; Rats, Wistar; Receptor, trkA
PubMed: 38599061
DOI: 10.1016/j.biopha.2024.116552 -
World Journal For Pediatric &... Nov 2023The anatomy of major aortopulmonary collateral arteries (MAPCAs) can be highly variable with regard to number, anatomic origin, course, and relationship to the native... (Review)
Review
The anatomy of major aortopulmonary collateral arteries (MAPCAs) can be highly variable with regard to number, anatomic origin, course, and relationship to the native pulmonary arteries. Some MAPCAs travel behind the esophagus (retroesophageal) and bronchus before entering the lung parenchyma. The purpose of this paper was to review the anatomy, physiology, and surgical characteristics of retroesophageal MAPCAs. This manuscript summarizes the data from a series of three papers that have focused on the subject of retroesophageal MAPCAs from our institution over the past ten years. Two-thirds of patients evaluated had a retroesophageal MAPCA identified at surgery. Retroesophageal major aortopulmonary collateral arteries (REMs) were more common with a left arch (77%) compared with a right arch (53%). Of all REMs evaluated, 83% were single supply, 13% were dual supply with an inadequate connection, and 4% were dual supply with an adequate connection. Based on these findings, 96% of retroesophageal MAPCAs were unifocalized. Follow-up catheterization was performed at a median of 17 months after surgery; 75% of unifocalized MAPCAs were widely patent, 20% were patent but stenotic, and 5% were occluded. The data demonstrate that retroesophageal MAPCAs are relatively common and almost always require unifocalization. At mid-term follow-up, 95% of unifocalized MAPCAs were found to be patent.
Topics: Humans; Infant; Pulmonary Atresia; Heart Defects, Congenital; Pulmonary Artery; Aorta, Thoracic; Collateral Circulation; Retrospective Studies
PubMed: 37499043
DOI: 10.1177/21501351231183970