Pulmonary Circulation Research Articles

Tricuspid regurgitation: a contemporary review.

Tricuspid regurgitation (TR), an underrecognized disease, overlooked by clinicians for many years due to its assumed benign nature. Recent epidemiological studies suggest significant TR may be seen in up to 6% of elderly patients. An increase in prevalence is expected due to the higher incidence of various clinical predictors of TR progression. Increasing severity of TR is associated with worse outcomes with a novel morphologic classification providing a more refined prediction of outcomes. Advances in cardiac imaging, particularly echocardiography, are integral to the diagnosis of disease severity which not only includes quantitation of TR, but also an assessment of the right atrium, right ventricle and pulmonary arterial circulation. Once identified and quantified, TR management requires a multi-disciplinary heart team management including structural imagers, heart failure specialists, electrophysiologist, cardiac surgeons and interventionalists. Data to support medical therapies are lacking although guidelines support the management of congestive signs and symptoms, as well as comorbidities such as left heart failure and rhythm management. The risks of surgical interventions are slowly improving, however, transcatheter therapies are now available to treat patients with high surgical risk. This manuscript will provide a state-of-art review of this fast-moving field, including current scientific evidences, but also upcoming perspectives with multiple ongoing clinical studies.

Patent ductus arteriosus stenting via femoral approach with wire twist technique: a case report

IntroductionPatent ductus arteriosus (PDA) stenting has emerged as a viable alternative to surgical interventions for ductus arteriosus-dependent pulmonary circulation. Several approaches and techniques have been reported but have had limited success.We present three cases of PDA stenting involving several types of PDA morphologies using the femoral vessel approach and introduce a highly successful technique.Case presentationCase 1: A 3-day-old female with pulmonary atresia and an intact ventricular septum had two stents implanted via the femoral artery (FA) in a PDA originating from the descending aorta. A 0.014-inch coronary guidewire was secured in the peripheral pulmonary artery (PA) to aid stent tracking, achieving postoperative oxygen saturation (SpO2) of 88%.Case 2: An 11-day-old male with pulmonary atresia and ventricular septal defect (PA/VSD) had a stent implanted in a PDA arising from the inferior aspect of the aortic arch via the femoral vein (FV). Postoperative SpO2 reached 92%.Case 3: A 2-month-old female with PA/VSD received two stents via the FA in a PDA originating from the innominate artery, achieving a postoperative SpO2 of 88%.ConclusionsThe wire twist technique is useful for implanting PDA stents through the transfemoral approach.

Idiopathic pulmonary hypertension in an adult with patent foramen ovale

The article is devoted to the clinical case of combined idiopathic pulmonary hypertension with an open foramen ovale of the atrial septum in a young man of 21 years old with progressive decrease in lung ventilation function. The relationship of pulmonary arterial hypertension with an open foramen ovale of the atrial septum is nearly not described in the literature, as it is rarely found in clinical practice. According to the classification, pulmonary hypertension is divided into idiopathic (primary), secondary and pulmonary hypertension caused by other causes. In the pathogenesis of any PAH, an important role belongs to a complex of vascular changes. Verification of vascular changes is carried out histologically. Variants of idiopathic pulmonary hypertension are plexiform and thrombotic arteriopathy, veno-occlusive disease, capillary hemangiomatosis. An open foramen ovale as a structural anomaly of the adult heart (a vestige of embryonic blood circulation) causes a variety of hemodynamic disorders that can affect the pathogenesis of pulmonary hypertension. Because of this, preclinical observation of a combination of plexiform and thrombotic arteriopathy with a patent foramen ovale of the interatrial septum in a young man of 21 years old and an attempt to determine the role of an open oval window in the progression of pulmonary hypertension and its effect on treatment is of interest. The diagnosis of idiopathic pulmonary hypertension was made based on the clinical picture, laboratory parameters, echocardiography and histological examination of pulmonary vessels. The article discusses the importance of a patent foramen ovale in the pathogenesis of idiopathic pulmonary hypertension.

Colchicine as a therapeutic option for the treatment of pulmonary arterial hypertension (PAH) in a rat model

Abstract Introduction Pulmonary arterial hypertension (PAH) is a cardiovascular disease that is characterized by severe structural and functional damages, resulting from the obstructive remodeling of the pulmonary vasculature and consequent right ventricular pressure overload. The current therapy mainly focuses on the pulmonary vascular system, with uncertain efficacy. Therefore, it is crucial to explore new therapeutic approaches. The mechanism of colchicine is complex and not-fully understood, but it has been proven to exert cardiopulmonary protective effects. Methods PAH induction was carried out in 8-week-old male WKY rats with a single subcutaneous injection of 60 mg/kg monocrotaline. Monocrotaline, a pyrrolizidine alkaloid, is metabolized in liver and induces inflammatory processes, which can cause PAH in rats. Starting from day 14 after MCT injection, the animals received three times a week intraperitoneal colchicine treatment at a dose of 0.5 mg/kg for two weeks. Echocardiographic examinations were performed during the study. At the end of the study, besides histological examination of the right ventricles and lungs [arterial wall thickness (WT%) and area (WA%)], the expression and phosphorylation levels of the proteins involved in cardiac remodeling were evaluated using Western blot. We assessed the pyruvate dehydrogenase (PDH) enzyme activity in the heart, which plays an important role in energy metabolism. We also examined the production of cytokines and chemokines in the right ventricle. Results The VW/BW ratio in the colchicine-treated group was significantly reduced compared to the MCT group (p<0.01). Echocardiographic parameters, EF% and E/e' ratio – characterizing the left ventricular function – did not differ considerably between the groups during the treatment. The TAPSE and PAT values characterizing right ventricular function improved in the MCT+C group (p<0.05). Collagen deposition and TGFβ level were significantly reduced by colchicine (p<0.05) in PAH animals. In the MCT+C group, the vascular remodeling (WT% and WA%) significantly decreased compared to the MCT group (p<0.01). The expression of α-SMA in vessel walls was most pronounced in the MCT group (p<0.01), which was significantly reduced by colchicine treatment. The phosphorylation of prosurvival signaling factors (ERK1/2, Akt1, GSK3β) was significantly increased in the MCT+C group (p<0.01) compared to the MCT group. In the right ventricle, PDH enzyme activity increased in the MCT+C group compared to the MCT group (p<0.01). According to cytokine array, cytokines involved in mediating fibrosis and inflammatory processes (TIMP-1, VEGF, L-selectin, CXCL7) showed increased secretion in the MCT group, which was moderately attenuated by colchicine treatment. Conclusion Colchicine treatment reduced the extent of fibrosis and inflammation, improved the structure of the pulmonary vasculature, and enhanced right ventricular function and energy supply.

Determinants of right ventricular - pulmonary arterial uncoupling in hypertrophic cardiomyopathy

Abstract Background Right ventricular (RV) – pulmonary arterial (PA) coupling, assessed by echocardiography, is a non-invasive surrogate on how the RV is adapted to an increased afterload in the pulmonary circulation. In cases of exhaustion of compensatory RV remodeling, the ratio decreases and there is RV-PA uncoupling. Our objective was to identify what are the determinants of this parameter in patients with hypertrophic cardiomyopathy (HCM). Methods This prospective cohort study enrolled patients with HCM without obstructive epicardial coronary artery disease, that underwent a comprehensive evaluation. Echocardiography was used to assess RV-PA coupling as the ratio of tricuspid annular plane systolic excursion (TAPSE) to pulmonary artery systolic pressure (PASP). In addition, coronary flow reserve in the left anterior descending artery (CFR_LAD) was also evaluated: diastolic coronary flow velocity was measured in basal conditions and in hyperemia and CFR was calculated as the ratio of hyperemic and basal peak diastolic flow velocities. This was used as a surrogate marker of coronary microvascular dysfunction. Cardiac magnetic resonance (CMR) was also performed to evaluate RV function (volumes and ejection fraction), and the extent of late gadolinium enhancement (LGE) in the left ventricle (LV). Results We enrolled 62 patients, with a mean age of 55 (15) years, 64% males. In 64% it was an asymmetrical septal hypertrophy phenotype, in 31% an apical hypertrophy, and in 27%, it was an obstructive HCM. Mean TAPSE/PASP was 0.556 (0.23) and median was 0.50. All patients had a normal LV ejection fraction. Univariable linear regression analysis showed that age, maximal wall thickness, E/E’, indexed left atrial volume (LAVi), CFR-LAD, %LGE and % hypoperfusion (by CMR) were correlated with RV-PA uncoupling. The HCM phenotype or the presence of obstruction were not associated with uncoupling. Multivariable stepwise linear regression analysis showed that the independent predictors of RV-PA uncoupling were age (b-estimate: - 0.180, p=0.009), LAVi (b-estimate: -0.645, p=<0.001), CFR-LAD (b-estimate: 0.183, p=0.011) and %LGE (b-estimate: -0.270, p=<0.001). Conclusion In patients with HCM, the presence of coronary microcirculation abnormalities and the extent of LGE in the LV are independent predictors of RV-PA uncoupling.

Prognostic value of left atrial strain in patients with moderate to severe mitral stenosis

Abstract Background Mitral stenosis causes an inflow restriction during diastole and is characterized by an increase in left atrial (LA) pressure with reduced cardiac output. Pressure overload of the LA can lead to atrial fibrosis and remodeling, resulting in a loss of LA reservoir and compliance capacity that can lead to backward load on the pulmonary circulation. To date, there are limited studies evaluating the impact of LA strain on prognosis of mitral stenosis patients. Purpose The aim of this study was to assess the prognostic value of LA strain in patients with moderate to severe mitral stenosis using two-dimensional (2D) strain imaging. Methods This was a single-center retrospective study, 237 patients with moderate or severe mitral stenosis were enrolled from January 2010 to December 2022. Baseline clinical and echocardiographic parameters were collected, LA strain measurements with reference time point at end diastole for reservoir strain (LASr), conduit strain (LAScd) and contraction strain (LASct) were analyzed using TOMTEC software. The endpoint was a composite outcome of all-cause mortality, heart failure hospitalization and valve intervention (percutaneous transvenous mitral commissurotomy and surgical intervention). All the LA parameters were analyzed separately to avoid collinearity. Results A total of 237 patients were included in the study. The patients had a mean age was 66.56 ± 13.61 years-old and were predominantly female (67.9%) with median follow up duration is 4.54 years (IQR 1.44 – 6.44). Mean left ventricular ejection fraction (LVEF) was 56.86 ± 10.51%, mean left atrium volume index (LAVI) was 73.94 ± 55.46 ml/m2, mean for LASr, LAScd and LASct were 11.81 ± 8.89%, -6.19 ± 4.50%, and -5.58 ± 6.05% respectively. LASr with a cut-off < 15.8% was independently associated with the composite outcome of all-cause mortality, heart failure hospitalization and valve intervention on multivariable Cox regression analysis (HR 2.51, 95% CI 1.54 - 4.10, p < 0.001). LAScd, LASct and LA volume index did not demonstrate any significant association with the endpoint. Conclusion LASr was independently associated with all-cause mortality, heart failure hospitalization and valve intervention in patients with moderate to severe mitral stenosis.

Echocardiographic assessment of the right heart pulmonary circulation unit in mitral regurgitation due to mitral valve prolapse

Abstract Background Right ventricular evaluation is essential in the context of chronic mitral regurgitation (MR). Chronic MR is associated with a progressive cardiac remodeling with enlargement and dysfunction of all cardiac chambers, and the development of functional tricuspid regurgitation (TR). Besides, right ventricle (RV) dysfunction and functional TR have been shown to influence patient prognosis. Purpose The aim of this study was to evaluate simple and combined echocardiographic parameters analysing the right heart – pulmonary circulation unit, according to the severity of MR. Methods In this monocentric retrospective study, echocardiographic studies of patients followed for a mitral valve prolapse (with or without MR) were reviewed. Usual parameters analysing RV morphology, load and function were obtained. Combined parameters of RV – pulmonary artery (RV-PA) coupling were calculated: TAPSE/PASP and RVFWS/PASP. Comparison between MR grades were performed with ANOVA or Kruskal Wallis tests as appropriate. Two-by-two post-hoc comparisons of continuous variables across the 5 groups were made using the Bonferroni correction. Results 158 patients with mitral valve prolapse (MVP) were included: 37 without MR, 28 with mild MR, 23 with mild-to-moderate MR, 21 with moderate-to-severe MR and 49 with severe MR. Clinical and echocardiographic results are presented in Table 1. Patients with a higher-grade MR tended to be older and were more likely to be men. They were also significantly more symptomatic. Most echocardiographic parameters were significantly different between grades of MR. RV remodeling, studied with morphologic parameters, started with the first grade of MR and had a linear progression between levels of MR severity (Figure 1A). Load parameters were stable until grade 2 and then showed progressive increase of RV afterload. RV free wall strain slightly increased with MR grade 1, and then decreased with each grade of MR (Figure 1B). RV fractional area change, Tissue Doppler MPI and RV free wall strain rate tended to stagnate between grade 0 and 2, and then they progressively decreased. Combined parameters of RV-PA coupling including load and function, increased with the first grade of MR, and then gradually decreased (Figure 1C). Conclusion In this study, multiparametric assessment of the cardiopulmonary unit in patients with MVP showed that RV morphologic remodeling starts with the first grades of MR, before any significant increase of pulmonary pressure. This remodeling seemed to initially enhance RV function (evaluated with parameters of RV – pulmonary artery coupling) in the first grade of MR and was then followed by a progressive decrease of RV function with the increasing severity of MR.

Glutathione s-transferase pi is a marker of loop diuretic resistance in patients with congestive heart failure exacerbation

Abstract Background Loop diuretic resistance (LDR) in patients with heart failure (HF) exacerbation is associated with worse clinical outcomes, greater symptom burden and mortality. Diagnosis and treatment of LDR remains a significant clinical dilemma. Purpose To assess the ability of different urine biomarkers to predict LDR in patients with HF exacerbation. Methods Consecutive patients with congestive HF exacerbation were prospectively included in the study. HF was diagnosed according to ESC 2021 HF Guidelines definition. Congestion was defined as a presence of one or more of the following signs: edema, ascites, pleural effusion. LDR was defined as persistent congestion on the 4th day of hospital stay despite high i.v. loop diuretic dose. Urine biomarkers released from different parts of the nephron (Kidney Injury Molecule-1 - KIM-1, N-acetyl-β-D-glucosaminidase - NAG, uromodulin, glutathione S-transferase Pi - pi-GST, aquaporin-2), transthoracic echo, clinical and biochemical parameters were evaluated on the 1st and 4th day of hospital stay. Results are presented as mean ±standard deviation or median (interquartile range). Results 40 patients were included in the study with median age 84 (72,8; 86) years, median left ventricle ejection fraction (EF) 35.3 (26,5; 49) %, median NT-proBNP 8967.5 (3024; 15241) pg/ml. LDR was found in 14 (35%) patients. Univariate analysis identified the following risk factors for LDR: urine pi-GST concentration on admission and on the 4th day, right ventricle to pulmonary circulation coupling index (TAPSE/PASP ratio), presence of mitral regurgitation, serum creatine concentration, serum urea concentration, serum LDL concentration. Logistic regression analysis identified pi-GST concentration as a significant independent risk factor for LDR in this population: odds ratio (OR) 5.75 [95% confidence interval (CI) 1.271–25.990]. Conclusions Urine pi-GST on admission and after 4 days of treatment might be a marker for a development of LDR in patients with congestive HF exacerbation.

The effect of exercise on RV-PC coupling in asymptomatic patients with significant primary mitral regurgitation

Abstract Background Right ventricular–pulmonary circulation (RV-PC coupling) serves as an index to evaluate RV function in relation to underlying RV afterload. Although impaired RV-PC coupling has been proposed as a predictor of adverse outcomes in heart failure (HF) patients with secondary mitral regurgitation (MR), there is limited data available for patients with primary MR. Purpose The objective of this study was to assess and compare alterations in RV-PC coupling during exercise with bicycle stress echocardiography in individuals with asymptomatic moderate to severe primary MR (MR group) and normal subjects (Control group). Μethods All patients and controls underwent stress echocardiography with a supine bicycle. RV systolic function was evaluated with TAPSE and S’. The non-invasively measured RV-PC coupling was evaluated by indexing TAPSE and S’ to right ventricular systolic pressure (RVSP) during baseline echocardiogram and peak workload stages of bicycle SE. Results Among the 48 patients in the MR group (mean age 53.5±15.16 years, 58.3% female), 39 patients had moderate MR(81.3%), 5 patients had moderate-to-severe MR(10.4%), and 4 patients had severe MR(8.3%). The duration of stress echocardiogram was significantly shorter in the MR group compared to control group (8.11±2.39 min vs 10.5±1.05 min, respectively; p<.001). Left Ventricular Ejection Fraction (LVEF) was within normal limits in both groups {70.7±11.9 % vs 72.6±12.1 %(p=NS} and the dimensions of left ventricular cavity (end-diastolic and end-systolic diameters) were significantly larger in the MR group compared to control group (49.25±5.21 mm vs 45.6±4.08mm (p .016) and 31.81±4.27mm vs 29.07±4.21mm (p .033) respectively}. TAPSE and RVSP increased from baseline to peak dose [23.48 ±3.05mm vs 29.94±3.48mm (p < .001), 8.54±4.56mmHg vs 43.79±5.27mmHg (p < .001), respectively]. There were no significant differences in TAPSE/RVSP and S’/RVSP between the two groups at rest. However, a significantly steady decrease was observed from baseline to peak dose (0.84±0.16 mm/mmHg vs 0.72±0.19mm/mmHg (p <.001) and 0.52±0.11 cm/sec/mmHg vs 0.50±0.15 cm/sec/mmHg (p .004), respectively). Conversely, these parameters did not exhibit a significant decrease in the control group. Finally, there was no significant correlation observed between the changes in the index TAPSE/RVSP , ratio E/E’ and systolic blood pressure. Conclusions RV-PC coupling decreases during exercise in asymptomatic patients with moderate to severe MR, independently of left ventricular dynamic changes. In contrast , there is no significant change in RV-PC coupling observed in the control group. Therefore, future studies should aim to evaluate the incremental role of this novel index not only in the assessment and evaluation of patients with MR but also as a potential prognostic marker.TAPSE/RVSP GraphTable of echocardiographic measurements

Exercise Doppler echocardiography to detect early changes in the right ventricular-pulmonary circulation unit after pulmonary embolism

Abstract Introduction After pulmonary embolism (PE), patients frequently complain about reduced exercise capacity and dyspnea on exertion, even without pulmonary hypertension (PH). The underlying condition is often chronic thromboembolic disease, which is caused by residual pulmonary obstruction with preserved resting pulmonary haemodynamics. The symptoms are the consequences of the increased dead space ventilation, exercise-induced PH and right ventricular (RV) dysfunction. We aimed to assess the pathologic differences in the echocardiographic parameters of the RV- pulmonary circulation unit among patients with previous PE and the healthy control group. Furthermore, an objective was to compare the hemodynamic response to stress after different treatment strategies (thrombolysis vs. heparin administration). Methods 21 patients after PE (mean age 58,5±12,1 years; 53% men) have been included in the study. All of them were effectively anticoagulated for at least three months, and none had any signs of PH on echocardiography at rest. The control group included 20 healthy volunteers (mean age 56,9±11,5 years; 55% men). Each patient underwent resting and exercise stress echocardiography on a semi-recumbent bicycle ergometer according to a standardised protocol until the maximally tolerated workload. Echocardiography was performed at rest, at 50 Watt workload and during peak stress. The measurements focused on the RV's systolic function (TAPSE), the estimated pulmonary artery systolic pressure (PASP), and the Doppler measurements in the RV and left ventricular outflow tracts. Pulmonary vascular resistance (PVR) and RV-pulmonary artery coupling (RV-PA) were calculated from the echocardiographic parameters. Results The post-PE group had significantly higher PASP (39,2 ±16,6 vs. 27,7±12,5 mmHg; p<0,05) and PVR (1,5±0,4 vs. 1,1±0,3 Wood Units; p<0,05) at peak stress, than the controls. 55% of post-PE patients remained symptomatic, but there were no significant differences between the symptomatic and asymptomatic groups regarding TAPSE, PASP, RV-PA coupling and PVR. 30% of post-PE patients had thrombolysis. In the patients where thrombolysis was performed, the coupling at peak stress was significantly higher than in heparin-treated patients (1,4±0,1 vs 0,9±0,4 mm/mmHg, p<0,05). Conclusion Post-PE patients without resting PH have higher PVR and PASP than the healthy control group, even after at least 3 months of adequate therapy. Post-PE patients treated with thrombolysis may have more preserved RV-PA coupling than the heparin-treated patients.

Catheter-directed treatment in acute pulmonary embolism

Abstract Background Pulmonary embolism (PE) is a potentially life-threatening emergency. PE occurs when venous thrombi embolize to the pulmonary circulation, resulting in vascular occlusion, impairing gas exchange and circulation. Initial risk stratification of acute PE is based on clinical symptoms, cardiac adaptations, comorbidities, and, in particular signs of haemodynamic instability. The primary aim of the treatment is to restore blood flow to the affected areas of the lungs, resolving/removing embolus burden and preventing further clot formation. In patients with severe PE, comprising decompensation or intended hemodynamic compromise, immediate reperfusion is recommended. Catheter-directed therapies (CDT) are an innovative treatment option for patients with severe PE to resolve embolus and restore pulmonic perfusion. These procedures are less invasive and are supposed to have a lower risk of bleeding complications compared to systemic thrombolysis or surgical embolectomy. Recent studies have shown that CDT are safe and effective treatment options for PE. Purpose Nevertheless, CDT have to demonstrate their non-inferiority and benefits regarding patients’ outcomes in real-world settings. Methods The German nationwide inpatient sample was used to identify and include all hospitalizations of patients with PE 2005-2020 in Germany. PE patients were stratified for use of CDT. Temporal trends of the usage and the impact of CDT on case-fatality and other outcomes were investigated (source: RDC of the Federal Statistical Office and the Statistical Offices of the federal states, DRG Statistics 2005-2020, own calculations). Results Overall, 1,373,084 hospitalisations of patients with PE (55.9% aged ≥70 years; 53.0% females) were included in this study 2005-2020. Among these, 427,238 (31.1%) were categorized as severe PE and 3330 (0.2%) were treated with CDT with an annual increase from 0.17% (2005) to 0.51% (2020). PE patients of younger age, male sex, with previous surgery, and with severe PE were more often treated with CDT. In patients with severe PE, CDT was attributed to lower MACCE (28.2% vs. 34.2%, P<0.001) and in-hospital case-fatality rate (24.9% vs. 31.0%, P<0.001), but higher prevalence of major bleeding (29.5% vs. 17.5%, P<0.001). CDT was associated with reduced MACCE (OR 0.91 [95%CI 0.83-0.99], P=0.031), a trend towards lower case-fatality (OR 0.92 [95%CI 0.84-1.01], P=0.068), but increased major bleeding (OR 2.12 [95%CI 1.92-2.33], P<0.001) in severe PE. The benefit of CDT regarding case-fatality was age-dependent, with the largest benefit in the 8th and 9th decade of life. Conclusions Although the annual rate of CDT increased from 2005 to 2020 in Germany, only 0.2% of the PE patients were treated with CDT. Selection criteria for CDT treatment were younger age, male sex, previous surgery, and severe PE. CDT treatment was associated with reduced MACCE and case-fatality rate in PE patients with severe PE.

Autonomic control of the pulmonary circulation: Implications for pulmonary hypertension.

The autonomic regulation of the pulmonary vasculature has been under-appreciated despite the presence of sympathetic and parasympathetic neural innervation and adrenergic and cholinergic receptors on pulmonary vessels. Recent clinical trials targeting this innervation have demonstrated promising effects in pulmonary hypertension, and in this context of reignited interest, we review autonomic pulmonary vascular regulation, its integration with other pulmonary vascular regulatory mechanisms, systemic homeostatic reflexes and their clinical relevance in pulmonary hypertension. The sympathetic and parasympathetic nervous systems can affect pulmonary vascular tone and pulmonary vascular stiffness. Local afferents in the pulmonary vasculature are activated by elevations in pressure and distension and lead to distinct pulmonary baroreflex responses, including pulmonary vasoconstriction, increased sympathetic outflow, systemic vasoconstriction and increased respiratory drive. Autonomic pulmonary vascular control interacts with, and potentially makes a functional contribution to, systemic homeostatic reflexes, such as the arterial baroreflex. New experimental therapeutic applications, including pulmonary artery denervation, pharmacological cholinergic potentiation, vagal nerve stimulation and carotid baroreflex stimulation, have shown some promise in the treatment of pulmonary hypertension.

Advances in Physiological Research: Consideration on Arterial Hypercapnia in Acute Cardiogenic Pulmonary Edema (ACPE)

The causes of hypercapnia in Acute Cardiogenic Pulmonary Edema are still unknown. Our hypothesis recognizes an alteration of the ventilation-perfusion ratio in the apical areas of the lung as the major cause. The redistribution of blood to the apical lung zone in hypertensive pulmonary circulation determines an excess of perfusion compared to ventilation and consequently hypercapnia. Our suggestion might be in favor of Bilevel-PAP over Continuous Positive Airway Pressure (CPAP) as the first line of therapy.

Appraisal of partial anomalous pulmonary venous drainage through a lumped-parameter mathematical model: a new pathophysiological proof of concept.

Haemodynamic determinants of the ratio between pulmonary and systemic flow (Qp/Qs) in partial anomalous pulmonary venous return (PAPVR) are still not fully understood. Indeed, among patients with the same number of lung segments draining anomalously, a great variability is observed in terms of right ventricular overload. The aim of this study was to test the hypothesis that the anatomic site of drainage, affecting the total circuit impedance, independently influences the magnitude of shunt estimated by Qp/Qs. A zero-dimensional (0D) lumped parameter mathematical model was developed and validated on a sample of patients. We developed a 0D lumped parameter model, using time varying elastances for heart chambers, RLC Windkessel circuits for the systemic and pulmonary circulations. Patients, were categorized into vena cava (VC) type (including left drainage to anomimous vein) and right atrium type (RA). The mathematical model is a system of ordinary differential equations that are numerically solved by means of the ode15s solver in the Matlab environment. The model showed an increase of Qp/Qs with the increase of the number of anomalous veins. With the same number of anomalous veins, Qp/Qs was lower in patients with anomalous drainage to the vena cava (VC) as compared with right atrium (RA) The validation sample consisted of 49 patients (27, 55% females). As predicted by the model, patients with PAPVR with VC type displayed a lower invasive and CMR Qp/Qs as compared with drainage to RA: 1.4 (1.2-1.7) and 1.45 (1.25-1.6) versus 2 (1.75-2.1) and 1.9 (1.6-2) p < 0.05. After stratifying for number of lung territories a lower Qp/Qs was measured in patients with VC PAPVR as compared with RA. In patients with PAPVR, the site of anomalous drainage modulates the Qp/Qs. According to the model, this effect is mediated by the post-capillary impedance of the circuit and significantly decreases with the increase of pulmonary vascular resistances.

Incidence and risk factors of postoperative delirium in lumbar spinal fusion patients: A National Database analysis

Postoperative delirium (POD) is a frequent complication observed in patients following spinal surgeries. The incidence of POD is particularly concerning for major procedures like lumbar spinal fusion, leading to a range of detrimental outcomes. However, existing research on the prevalence and risk factors associated with POD after lumbar spinal fusion is limited, especially when relying on data from large-scale national databases. This study employed a comprehensive analysis of the National Inpatient Sample (NIS) database, encompassing data from 2010 to 2019. The study population included patients who underwent primary lumbar spinal fusion surgery. We compared patients who did not experience POD with those who developed POD postoperatively, analyzing demographic characteristics, pre-existing comorbidities, and perioperative complications. Analysis of the NIS database identified a total of 493,481 patients who underwent lumbar spinal fusion. The overall incidence of POD following the procedure was 1.07%. Patients who experienced delirium postoperatively exhibited significantly longer hospital stays, incurred higher healthcare costs, and faced a heightened risk of in-hospital mortality (p < 0.001). Additionally, POD following lumbar spinal fusion was associated with various medical complications, including acute renal failure, myocardial infarction, pneumonia, pulmonary embolism, stroke, and urinary tract infections. Several independent predictors were identified as being significantly associated with postoperative delirium, including advanced age (≥65 years old), pre-existing neurological disorders, a history of alcohol or drug abuse, depression, psychotic disorders, fluid and electrolyte imbalances, diabetes, weight loss, deficiency anemia, coagulopathy, congestive heart failure, pulmonary circulation disorders, peripheral vascular disease, chronic renal insufficiency, and receiving treatment at a teaching hospital. Notably, neurological disorders demonstrated the strongest correlation with the development of postoperative delirium. Overall, our analysis revealed a relatively low prevalence of POD following lumbar spinal fusion surgery. Nevertheless, it is critical to investigate and understand the independent predictors of POD to effectively prevent and mitigate its negative impact on patient outcomes.

Benzo (A) pyrene exposure alters alveolar epithelial and macrophage cells diversity and induces antioxidant responses in lungs

This study was designed to investigate the toxic effects of benzo (a) pyrene (BaP) in the lungs. Mice were repeatedly treated orally with BaP (50 mg/kg body weight, twice a week for four weeks) to induce a tumour. After 4 months of BaP administration, tumours were visible beneath the skin. The histopathological section of the lungs shows congestion of pulmonary blood vessels, alveolar hyperplasia, and concurrent epithelial hyperplasia with infiltrates of inflammatory cells also seen. Thereafter, a single-cell suspension of lung tissues was stained with fluorescently conjugated antibodies for the demarcation of alveolar epithelial (anti-mouse CD74 and podoplanin) and macrophage (F4/80 and CD11b) cells and measured by flow cytometry. The expression of antioxidant genes was assessed by qRT–PCR. The number of alveolar epithelial cells 1 (AEC1) increased, but the number of alveolar epithelial cells 2 (AEC2) and transitional alveolar epithelial cells (TAEC) was significantly decreased in tumour-bearing mice. The proportion of CD11b+ alveolar macrophages (AM) and interstitial macrophages (IM) was increased, but the proportion of F4/80+ AM cells was reduced. The BaP administration significantly increased the ROS production in alveolar cells. The relative expression levels of antioxidant genes (SOD1, catalase, GPX1, and HIF-1α) were increased, but NRF2 expression was decreased in BaP-treated alveolar cells. The expression of anti-inflammatory (NF-κB) was also significantly increased. In conclusion, BaP exposure induced an inflammatory response, altered alveolar epithelial cell and macrophage diversity, and increased antioxidant responses in the lungs.

Evaluating fetal pulmonary vascular development in congenital heart disease: a comparative study using the McGoon index and multiple parameters of fetal echocardiography.

The purpose of this study was to evaluate the value of MGI and multi-parameter in the assessment of different pulmonary circulation blood volumes in congenital heart disease. This study included 350 fetuses categorized into two groups: Normal group consisted of 258 fetuses with no discernible abnormalities through echocardiography as control Group A; Abnormal group with abnormal echocardiogram, including Group B of 71 fetuses with decreased pulmonary blood flow or pulmonary atresia and Group C of 21 fetuses with reduced or detached aortic blood flow. The MGI and Z-scores were measured and compared among these groups. Significant variations were noted in the aortic outflow Z-scores (AO-Zs) (p<0.01), pulmonary artery (PA) (p<0.01), PA Z-scores (PA-Zs) (p<0.01), PA/AO (p<0.01), right PA (p<0.01), and MGI (p<0.01) among the three groups (all p<0.05). Among fetuses with decreased pulmonary blood flow or pulmonary atresia, PA, PA-Zs, and MGI in fetuses with reverse DA flow perfusion were lower than those in the DA forward perfusion group. Fetal echocardiography, incorporating the MGI and multi-parameter, not only allows for the evaluation of pulmonary blood flow and pulmonary vascular development of the fetus but also enables the observation of changes in pulmonary blood flow and MGI development across different gestational weeks.

Do Hemodynamic Definitions of Chronic Thromboembolic Pulmonary Hypertension Distinguish Between Distinct Phenotypes of Chronic Thromboembolic Pulmonary Disease?

Chronic thromboembolic pulmonary disease (CTEPD) is defined by chronic organized thrombi in the pulmonary circulation without or with pulmonary hypertension (CTEPH). The current definition of CTEPH has adopted lower mean pulmonary artery pressure (mPAP) and pulmonary vascular resistance (PVR) thresholds. Our aim was to identify its impact on the characterization of patients with CTEPD. All consecutive CTEPD patients referred for cardiopulmonary exercise testing (CPET) in a PH center were divided into four groups based on pulmonary haemodynamics. Group A: mPAP≤20 mmHg, Group B: mPAP>20 mmHg with PVR>2 and ≤3 WU, Group C: mPAP>20 mmHg with PVR>3 WU, Group D: mPAP>20 mmHg with PVR<2 WU (''unclassified''). We compared CPET, CT pulmonary angiography, and MRI data across the groups. There was mild aerobic capacity impairment, mild/moderate ventilatory inefficiency, and no significant cardiac limitation on CPET in all groups. However, patients in Groups A and D had better ventilatory efficiency and less oxygen desaturation on exercise due to lower dead-space ventilation. There was no difference in chronic pulmonary emboli burden and distribution, or resting RV function between the groups. Seventeen patients were reclassified as having ''CTEPH'' based on the current definition. No functional deterioration was noted within a median period of 13 months on repeat CPET. CTEPD patients with similar clot burden and RV function without or with mild/moderate PH displayed a similar pattern of cardiopulmonary limitation, except for ventilatory efficiency. The current definition for CTEPH may lead to reclassification of CTEPH in a considerable number of patients.

Diagnosis, Management and Outcome of Truncus Arteriosus Communis Diagnosed during Fetal Life-Cohort Study and Systematic Literature Review.

Background/Objectives: Truncus arteriosus communis (TAC) is a rare congenital heart defect characterized by a single arterial trunk that supplies systemic, pulmonary, and coronary circulations. This defect, constituting approximately 1-4% of congenital heart diseases, poses significant challenges in prenatal diagnosis, management, and postnatal outcomes. Methods: A retrospective analysis was conducted at the local tertiary referral center on cases of TAC diagnosed prenatally between 2019 and 2024. Additionally, a systematic literature review was performed to evaluate the accuracy of prenatal diagnostics and the presence of associated anomalies in fetuses with TAC and compare already published data with the local results. The review included studies that especially described the use of fetal echocardiography, the course and outcome of affected pregnancies, and subsequent management strategies. Results: The analysis of local prenatal diagnoses revealed 14 cases. Of the 11 neonates who survived to birth, the TAC diagnosis was confirmed in 7 instances. With all seven neonates undergoing surgery, the intention-to-treat survival rate was 86%, and the overall survival rate was 55%. By reviewing published case series, a total of 823 TAC cases were included in the analysis, of which 576 were diagnosed prenatally and 247 postnatally. The presence of associated cardiac and extracardiac manifestations as well as genetic anomalies was common, with a 22q11 microdeletion identified in 27% of tested cases. Conclusions: Advances in prenatal imaging and early diagnosis have enhanced the management of TAC, allowing for the detailed planning of delivery and immediate postnatal care in specialized centers. The frequent association with genetic syndromes underscores the importance of genetic counseling in managing TAC. An early surgical intervention remains crucial for improving long-term outcomes, although the condition is still associated with significant risks. Long-term follow-up studies are essential to monitor potential complications and guide future management strategies. Overall, a coordinated multidisciplinary approach from prenatal diagnosis to postnatal care is essential for improving outcomes for individuals with TAC.

Nintedanib preserves lung growth and prevents pulmonary hypertension in a hyperoxia-induced lung injury model.

Bronchopulmonary dysplasia (BPD), the chronic lung disease associated with prematurity, is characterized by poor alveolar and vascular growth, interstitial fibrosis, and pulmonary hypertension (PH). Although multifactorial in origin, the pathophysiology of BPD is partly attributed to hyperoxia-induced postnatal injury, resulting in lung fibrosis. Recent work has shown that anti-fibrotic agents, including Nintedanib (NTD), can preserve lung function in adults with idiopathic pulmonary fibrosis. However, NTD is a non-specific tyrosine kinase receptor inhibitor that can potentially have adverse effects on the developing lung, and whether NTD treatment can prevent or worsen risk for BPD and PH is unknown. We hypothesize that NTD treatment will preserve lung growth and function and prevent PH in an experimental model of hyperoxia-induced BPD in rats. Newborn rats were exposed to either hyperoxia (90%) or room air (RA) conditions and received daily treatment of NTD or saline (control) by intraperitoneal (IP) injections (1 mg/kg) for 14 days, beginning on postnatal day 1. At day 14, lung mechanics were measured prior to harvesting lung and cardiac tissue. Lung mechanics, including total respiratory resistance and compliance, were measured using a flexiVent system. Lung tissue was evaluated for radial alveolar counts (RAC), mean linear intercept (MLI), pulmonary vessel density (PVD), and pulmonary vessel wall thickness (PVWT). Right ventricular hypertrophy (RVH) was quantified with cardiac weights using Fulton's index (ratio of right ventricle to the left ventricle plus septum). When compared with RA controls, hyperoxia exposure reduced RAC by 64% (p < 0.01) and PVD by 65% (p < 0.01) and increased MLI by 108% (p < 0.01) and RVH by 118% (p < 0.01). Hyperoxia increased total respiratory resistance by 94% and reduced lung compliance by 75% (p < 0.01 for each). NTD administration restored RAC, MLI, RVH, PVWT and total respiratory resistance to control values and improved PVD and total lung compliance in the hyperoxia-exposed rats. NTD treatment of control animals did not have adverse effects on lung structure or function at 1 mg/kg. When administered at higher doses of 50 mg/kg, NTD significantly reduced alveolar growth in RA controls, suggesting dose-related effects on normal lung structure. We found that NTD treatment preserved lung alveolar and vascular growth, improved lung function, and reduced RVH in experimental BPD in infant rats without apparent adverse effects in control animals. We speculate that although potentially harmful at high doses, NTD may provide a novel therapeutic strategy for prevention of BPD and PH. Anti-fibrotic therapies may be a novel therapeutic strategy for the treatment or prevention of BPD. High-dose anti-fibrotics may have adverse effects on developing lungs, while low-dose anti-fibrotics may treat or prevent BPD. There is very little preclinical and clinical data on the use of anti-fibrotics in the developing lung. Dose timing and duration of anti-fibrotic therapies may be critical for the treatment of neonatal lung disease. Currently, strategies for the prevention and treatment of BPD are lacking, especially in the context of lung fibrosis, so this research has major clinical applicability.