Search Results (96)

Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare, progressive form of pre-capillary pulmonary hypertension characterized by persistent, organized thromboemboli in the pulmonary vasculature, leading to vascular remodeling, elevated pulmonary artery pressures, right heart failure, and significant morbidity and mortality if untreated. Despite advances, CTEPH remains underdiagnosed due to nonspecific symptoms and overlapping features with other forms of pulmonary hypertension. Basic Methodology: This review synthesizes data from large international registries, epidemiologic studies, translational research, and multicenter clinical trials. Key methodologies include analysis of registry data to assess incidence and risk factors, histopathological examination of lung specimens, and molecular studies investigating endothelial dysfunction and inflammatory pathways. Diagnostic modalities and treatment outcomes are evaluated through observational studies and randomized controlled trials. Recent Advances and Affected Population: Research has elucidated that CTEPH arises from incomplete resolution of pulmonary emboli, with subsequent fibrotic transformation mediated by dysregulated TGF-β/TGFBI signaling, endothelial dysfunction, and chronic inflammation. Affected populations are typically older adults, often with prior venous thromboembolism, splenectomy, or prothrombotic conditions, though up to 25% have no history of acute PE. The disease burden is substantial, with delayed diagnosis contributing to worse outcomes and higher societal costs. Microvascular arteriopathy and PAH-like lesions in non-occluded vessels further complicate the clinical picture. Conclusions: CTEPH is now recognized as a treatable disease, with multimodal therapies—surgical endarterectomy, balloon pulmonary angioplasty, and targeted pharmacotherapy—significantly improving survival and quality of life. Ongoing research into molecular mechanisms and biomarker-driven diagnostics promises earlier identification and more personalized management. Multidisciplinary care and continued translational investigation are essential to further reduce mortality and optimize outcomes for this complex patient population. Full article

Systemic sclerosis (SSc) is a heterogeneous disease characterized by vascular alterations, immune dysregulation, and fibrosis. Solid evidence supports the hypothesis that endothelial dysfunction is the key player in SSc vascular injury and a critical factor concurring to the initiation of SSc pathogenesis. This narrative review reports on persistent endothelial dysfunction, resulting from oxidative stress, autoimmunity, and impaired vascular repair, in the course of SSc, and how it can trigger and sustain fibrotic remodeling of various organs. In this paper, we also analyze the impact on SSc of impaired angiogenesis and vasculogenesis, diminished endothelial progenitor cell function, and endothelial-to-mesenchymal transition, which can collectively disrupt vascular homeostasis and promote myofibroblast activation. These pathologic events underlie the hallmark clinical manifestations, i.e., Raynaud’s phenomenon, digital ulcers, pulmonary arterial hypertension, and scleroderma renal crisis. The review highlights how recognizing SSc as a paradigm of systemic endothelial dysfunction may reframe our understanding of its physiopathology, modify current therapeutic strategies, and unveil new therapeutic targets. Full article

Background: The progressive course of coronavirus disease 2019 (COVID-19) is more frequently observed in individuals with obesity, diabetes, pulmonary and cardiovascular disease, or arterial hypertension. Many patients with these conditions are prescribed statins to treat hypercholesterolaemia. However, statins exhibit additional pleiotropic effects. The present study aims to investigate the effects of all eight currently existing statins on the expression of genes whose products have been reported to be directly associated with complicated COVID-19 disease. Methods: We extended the interpretation of the whole-genome DNA microarray analyses of pancreatic cancer cells MiaPaCa-2 and whole-transcriptome analyses of adipose tissue-derived mesenchymal stem cells AD-MSC that we had performed in the past. From the number of genes with altered expression induced by statins, we focused on those reported to be involved in a complicated course of COVID-19, including APOE and ACE2, genes encoding proteins involved in innate antiviral immunity and respiratory failure genes. Results: Although we did not observe statin-induced changes in the expression of APOE, ACE2 and any of the six genes clustered in the locus associated with respiratory failure in patients with COVID-19, some statins induced changes in the expression of genes encoding their interaction partners. Among genes associated with the immune system, all statins, which are effective in vitro affected the expression of genes encoding IL-6 and IL-8 and interaction partners of NF-kB, which may influence the duration of viral persistence. Conclusions: Statins act on multiple pathways simultaneously, some of which support COVID-19 development, while others suppress it. Full article

Objective: The aim of this study was to describe the presenting characteristics and outcomes of neonates with respiratory failure referred for extracorporeal membrane oxygenation (ECMO) support, compare those who received ECMO support (ECMO group) to those who did not (non-ECMO group), and evaluate the predictive variables requiring ECMO support. Methods: All neonates (<15 days) with respiratory failure (without congenital diaphragmatic hernia or congenital heart disease) referred to our regional ECMO center from 2014 to 2023 were included in this retrospective study. Patient demographics, birth history, and clinical and outcome variables were analyzed. Oxygenation indices and vasoactive–inotropic scores obtained at PICU arrival and four hours after arrival were compared between the two groups using ROC analysis, with ECMO initiation as an outcome variable. Youden’s index was used for optimal threshold values. Chi-square, Mann–Whitney U, and binary logistic regression were used for comparative analyses. Results: Out of the 147 neonates, 96 (65%) required ECMO support. The two groups significantly differed in the prevalence of pulmonary hypertension (pHTN; systemic or suprasystemic pulmonary pressures), lactate level, and oxygenation indices. Mortality was not different between the two groups. Presence of oxygen saturation index (OSI) ≥ 10 had a sensitivity 96.8% in predicting the need for ECMO support. On regression analysis, OSI and pHTN were independent predictors of ECMO support. Conclusions: Oxygenation indices and echo findings predict the need for ECMO support in neonatal hypoxemic respiratory failure. These findings help non-ECMO centers make appropriate and timely transfers of neonates with respiratory failure to ECMO centers. Full article

Background/Objectives: To identify the risk factors and clinical outcomes of persistent pulmonary hypertension of the newborn (PPHN) in very low birth weight (VLBW) infants in a resource-limited setting. Methods: We conducted a 1:4 matched case–control study in a Thai neonatal unit between 2014 and 2023. Neonates born at a gestational age (GA) < 32 weeks and with a birth weight (BW) < 1500 g were included. Neonates who died in the delivery room or had major congenital anomalies were excluded. Matching was based on GA, BW, year of birth, and endotracheal intubation at birth. Conditional logistic regression analysis was performed. Results: Over the 10-year study period, the incidence of PPHN among VLBW neonates was 4.6% (31/667). After matching, there were 31 cases and 124 controls. In univariable analysis, PPHN was significantly associated with lower 1 min and 5 min Apgar scores; however, no significant association remained in multivariable analysis. PPHN was significantly associated with composite adverse outcomes—including mortality and major morbidities (adjusted odds ratio [aOR] = 7.51, 95% confidence interval [CI]: 2.41–23.40), mortality alone (aOR = 2.88, 95% CI: 1.06–7.63), major morbidities (aOR = 2.99; 95% CI: 1.29–6.95), and severe neurological injury (aOR = 4.44, 95% CI: 1.56–12.59). Daily hospital costs were also higher in PPHN cases, with an average increase of 97.1 USD. Conclusions: In VLBW infants, PPHN was associated with a lower Apgar score and surfactant administration. PPHN was significantly linked to adverse outcomes, particularly mortality, major morbidities, and severe neurological injury. Full article

Background/Objectives: Persistent pulmonary hypertension of the newborn (PPHN) is characterized by increased pulmonary vascular resistance, resulting in severe hypoxemia. This study determined the factors associated with increased risk of mortality and survival rate in infants with PPHN. Methods: This retrospective study was conducted between 2010 and 2023. The risk factors for mortality were assessed by Cox’s proportional hazard models, and the Kaplan–Meier survival curve was used to analyze the survival rates. Results: This study included 233 neonates with PPHN. Gestational age (GA) less than 28 weeks (adjusted hazard ratio [AHR] = 5.46, 95% confidence interval [CI]: 2.25–13.24, p < 0.001), Small for gestational age (SGA) (AHR = 2.93, 95% confidence interval [CI]: 1.24–6.92, p = 0.026), acute kidney injury (AKI) (AHR = 2.48, 95% CI: 1.27–4.84, p = 0.01), pneumothorax (AHR = 3.03, 95% confidence interval [CI]: 1.48–6.21, p = 0.003), vasoactive-inotropic score (VIS) at 24 h of age (AHR = 1.0026, 95% confidence interval [CI]: 1.0004–1.005, p = 0.026), and score for neonatal acute physiology II (SNAP-II) ≥ 43 (AHR = 4.03, 95% CI: 1.66–9.77, p = 0.005) were associated with an increased risk of mortality. The overall survival rate was 82.4%; it rose from 63.8% to 87.1% after inhaled nitric oxide (iNO) and extracorporeal membrane oxygenation (ECMO) were introduced (p < 0.001). The cumulative survival rates at the end of the 30 days were 62.1% (95% CI: 49.0–78.7) in the Pre-iNO era and 87.5% (95% CI: 82.7–92.6) in the Post-iNO/ECMO era, respectively (p < 0.001). Conclusions: GA less than 28 weeks, SGA, AKI, pneumothorax, high VIS and SNAP-II scores were associated with mortality in infants with PPHN. The improvement in the survival rate was related to the provision of advanced care, including iNO and ECMO therapy. Full article

Background: The aim of this study was to describe our centre experience in the use of pulmonary vasodilator therapy in Fontan patients. Methods: We retrospectively enrolled patients that underwent Fontan operation between 2000 and 2024, reporting demographic and operative data and noting complications and the use of pulmonary vasodilators. Results: A total of 117 patients were followed for a median time of 150 months (90–207). In total, 36.7% were female, and the median age during the intervention was 50 months (37–64), and 53% had a single left ventricle physiology. In 20 of these 117 patients (17.1%), at least one pulmonary vasodilator drug was used during their life for the following reasons: 6 elevated pressures in the circuit, 3 low oxygen saturation, 2 plastic bronchitis, 2 pleural effusion, 1 chylothorax, 1 persistent pericardial effusion, 1 haemoptysis, 1 protein losing enteropathy, 1 poor exercise tolerance, 1 pulmonary arterial hypertension present since birth and 1 diastolic dysfunction. They had a significantly higher prevalence of single right ventricle physiology (65% vs. 37%, p = 0.03), pulmonary hypertension (60% vs. 0, p = 0.0001), plastic bronchitis (10% vs. 0, p = 0.03) and declivous oedema in the follow-up period (10% vs. 0, p = 0.03), with a higher assumption of warfarin (35% vs. 6.2%, p = 0.001). Conclusions: We found that in the absence of a standardise protocol, we usually use pulmonary vasodilator therapy in Fontan patients, as it is guided by clinical aspects and hemodynamic conditions, which lead us to start and stop this therapy. Full article

Background: Human Immunodeficiency Virus (HIV) infections remain a source of cardiopulmonary complications among people receiving antiretroviral therapy. Still to this day, pulmonary hypertension (PH) severely affects the prognosis in this patient population. The persistent expression of HIV proteins, even during viral suppression, has been implicated in vascular dysfunction; however, little is known about the specific effects of these proteins on the pulmonary vasculature. This study investigates the impact of Nef variants derived from HIV-positive pulmonary hypertensive and normotensive donors on pulmonary vascular cells in vitro. Methods: We utilized well-characterized Nef molecular constructs to examine their effects on cell adhesion molecule gene expression (ICAM1, VCAM1, and SELE), pro-apoptotic gene expression (BAX, BAK), and vasoconstrictive endothelin-1 (EDN1) gene expression in endothelial nitric oxide synthase (eNOS) nitric oxide and the production and secretion of pro-inflammatory cytokines over 24, 48, and 72 h post-transfections with Nef variants. Results: HIV Nef variants SF2, NA7, and PH-associated Fr17 and 3236 induced a significant increase in adhesion molecule gene expression of ICAM1, VCAM1, and SELE. Pulmonary normotensive Nef 1138 decreased ICAM1 gene expression, but had increased VCAM1. PH Nef ItVR showed a consistent decrease in ICAM1 and no changes in SELE and VCAM1 expression. Further gene expression analyses of pro-apoptotic genes BAX and BAK demonstrated that Nef NA7, SF2, normotensive Nef 1138, and PH Nef Fr8, Fr9, Fr17, and 3236 variants significantly increased gene expression for apoptosis. Normotensive Nef 1138, as well as PH Nef Fr9 and ItVR, all displayed a statistically significant decrease in BAX expression. The expression of EDN1 had a statistically significant increase in samples treated with Nef NA7, SF2, normotensive Nef 2044 and PH Nef 3236, Fr17, and Fr8. Notably, PH-associated Nef variants sustained pro-inflammatory cytokine production, including IL-2, IL-4, and TNFα, while anti-inflammatory cytokine levels remained insufficient. Furthermore, eNOS was transiently upregulated by all Nef variants except for normotensive Nef 2044. Conclusions: The distinct effects of Nef variants on pulmonary vascular cell biology highlight the complex interplay between Nef, host factors, and vascular pathogenesis according to the variants. Full article

Background: Following acute pulmonary embolism (PE), disease outcomes vary among patients. Complete recovery occurs in some cases, while others may experience persistent long-term symptoms, disease recurrence, or progression to chronic thromboembolic pulmonary hypertension (CTEPH). The exact reasons behind incomplete recovery and different outcomes are still not well established. This review aims to present the existing data regarding the clinical significance of residual thrombi after acute PE, particularly in the context of disease recurrence, the development of CTEPH, or persistent symptoms and functional limitations. Methods: Original articles, systematic reviews, and meta-analyses relevant to the topic are reviewed. Results: Incomplete thrombus resolution after acute PE is quite common, with studies showing that it affects one-fourth to one-third of PE patients, despite receiving optimal anticoagulant treatment. It has been shown that residual thrombi after acute PE play a role in the risk of PE recurrence. However, there is still no standardized method to differentiate disease recurrence from residual thrombi in pulmonary imaging studies, particularly in cases where no follow-up scans and different imaging techniques are used for thrombi detection. Residual vascular obstruction is necessary for the development of CTEPH. Evidence suggests that the extent of residual thrombi contributes to a higher risk of CTEPH. Still, there is a need to standardize both the timing of residual thrombi assessment and the evaluation of their distribution, in relation to the development of CTEPH. The significance of residual thrombi for persistent symptoms and functional limitation remains debatable. Research indicates that nearly half of patients experience long-term symptoms after acute PE. Still, it is believed that these symptoms are not necessarily caused only by residual thrombi, but rather by the worsening of other comorbid conditions. Conclusions: Studies show that residual thrombi after acute PE are significant for PE outcomes. It may be beneficial to consider evaluating residual pulmonary vascular obstruction when treating patients after acute PE to optimize the duration of anticoagulant therapy and improve patient outcomes. Full article

Background/Objectives: Growth failure is a common complication in children with congenital heart disease (CHD), yet its underlying mechanisms and consequences remain incompletely understood. This review aims to provide a comprehensive overview of growth failure in children with CHD and outline a framework of factors contributing to this condition. Methods: To lay the foundation for this narrative review, several databases were searched using broad search terms related to CHD and growth failure. Results: Growth failure is most pronounced during the first year of life, but often improves after achieving hemodynamic stability through surgical or medical interventions. However, children with complex conditions, such as single-ventricle physiology or multiple heart defects, may experience persistent growth impairment due to chronic disease effects. Specific features of CHD—cyanosis, pulmonary hypertension, and low cardiac output—can further hinder growth by disrupting endocrine function and impairing musculoskeletal development. Long-term use of medications and exposure to repeated diagnostic procedures also contribute to growth failure. Beyond physical effects, growth failure profoundly influences neurodevelopment, psychosocial well-being, and survival outcomes. Based on our review, we have developed a knowledge map to better understand the complexities of growth failure in children with CHD. Conclusions: A thorough understanding of the multifaceted contributors to growth failure in CHD is essential for identifying high-risk children and devising strategies to support optimal growth. Integrating this knowledge into clinical practice can improve long-term outcomes for children with CHD. Full article

Background/Objectives: Hypoxic–ischemic encephalopathy (HIE), affecting 1.3–1.7/1000 live births, is treated with conventional therapeutic hypothermia (TH) but carries significant mortality and neurological impairment. Here, we compared intravascular cooling with extracorporeal membrane oxygenation (ECMO) and conventional TH in neonates with moderate to severe HIE. Methods: We retrospectively analyzed single-center neonates born in 2000–2022. Neonates with a 10 min Apgar score ≤ 3 or umbilical artery pH ≤ 6.7, along with persistent pulmonary hypertension of the newborn and an oxygenation index of ≥25 to <40, were divided into ECMO (n = 17) and conventional TH (n = 18) groups and administered the Kyoto Scale of Psychological Development at 18 months. Results: Neonatal and maternal characteristics were similar between the groups. A significantly higher proportion of the ECMO group (70.6% vs. 33.3%) achieved a developmental quotient ≥ 70. Conclusions: Intravascular cooling with ECMO may improve the neurodevelopmental outcomes of neonates with HIE, severe acidosis, and low Apgar scores. Full article

Pulmonary hypertension (PH) is a progressive disorder characterized by obstructive changes in the pulmonary vasculature, leading to increased pulmonary vascular resistance (PVR), right ventricular (RV) strain, and eventual RV failure (RVF). Despite advancements in medical therapy, PH remains associated with significant morbidity and mortality, particularly in children. RVF is a clinical syndrome resulting from complex structural and functional remodeling of the right heart, leading to inadequate pulmonary circulation, reduced cardiac output, and elevated venous pressure. Management paradigms for pediatric PH diverge significantly from those in adults, particularly due to the predominance of congenital heart disease (CHD) and the dynamic nature of pediatric cardiovascular and pulmonary development. CHD remains a principal driver of PH in children, and its associated pathophysiology demands a nuanced approach. In patients with unrepaired left-to-right shunts, elevated pulmonary blood flow can lead to progressive pulmonary vascular remodeling and increased PVR. The postoperative persistence or progression of PH may occur if irreversible vascular changes have already developed. Current PH treatments primarily focus on reducing PVR, yet distinguishing between therapeutic approaches that target the pulmonary vasculature and those aimed at improving RV function remain challenging. In pediatric patients with progressive PH despite optimal therapy, additional targeted interventions may be necessary to mitigate RV dysfunction and disease progression. This review provides a comprehensive analysis of the mechanisms underlying RVF in PH, incorporating insights from clinical studies in adults and experimental models, while highlighting the unique considerations in children. Furthermore, it explores current pharmacological and interventional treatment strategies, emphasizing the need for novel therapeutic approaches aimed at directly reversing RV remodeling. Given the complexities of RV adaptation in pediatric PH, further research into disease-modifying treatments and innovative interventions is crucial to improving long-term outcomes in affected children. Full article

Background: Heart failure (HF) is a progressive condition associated with reduced life expectancy and quality of life. Atrial fibrillation (AF), the most common arrhythmia in HF patients, significantly worsens symptoms and outcomes. The coexistence of HF and AF is linked to higher morbidity and mortality rates, with a bidirectional relationship exacerbating both conditions. The recent evidence has suggested that combining pulmonary vein isolation (PVI) with renal denervation (RDN) may offer a promising strategy for reducing AF burden and enhancing patient outcomes. Methods: This prospective interventional clinical trial aimed to assess the safety and effectiveness of a combined RDN and PVI approach compared to PVI alone. Eighteen patients, aged 18 to 80 years, with paroxysmal or persistent AF and HF (left ventricular ejection fraction [LVEF] < 50%) were enrolled. RDN was performed under general anesthesia using the four-electrode Symplicity Spyral catheter and Symplicity G3 radiofrequency generator (Medtronic). Patients were randomized to the RDN+PVI group (n = 7) or the PVI-only group (n = 11). The groups were similar in age (59 ± 8.4 years vs. 62.5 ± 11.08 years, p = NS) and baseline characteristics, including hypertension, obesity, and impaired left ventricular function (LVEF 35.86% vs. 38.54%, RDN+PVI vs. PVI only; p = NS). Results: Over a mean follow-up of 24 months, one patient died, ten were hospitalized, six underwent repeat PVI, and eight achieved AF freedom. Patients in the RDN+PVI group were significantly more likely to remain AF-free (n = 6 vs. 2; p = 0.0063). The need for repeat ablation was higher in the PVI-only group (54.5% vs. 0%), though this did not reach statistical significance. Hospitalization rates and changes in ejection fraction were similar between groups. Importantly, no procedural complications were observed. Conclusions: Combining RDN with PVI is a safe hybrid approach for AF management in HF patients, showing promising efficacy in reducing AF recurrence. Larger randomized studies are needed to confirm these findings and further explore this novel therapeutic strategy. Full article

Respiratory diseases are major health concerns worldwide. Chronic respiratory diseases (CRDs) are the third leading cause of death worldwide and some of the most common are chronic obstructive pulmonary disease (COPD), asthma, occupational lung diseases, and pulmonary hypertension. Despite having different etiology and characteristics, these diseases share several features, such as a persistent inflammatory state, chronic oxidative stress, impaired mucociliary clearance, and increased alveolar surface tension. CRDs are not curable; however, various forms of treatment, that help restore airway patency and reduce shortness of breath, can improve daily life for people living with these conditions. In this regard myo-inositol may represent a valid therapeutic adjuvant approach due to its properties. Being a redox balancer, an inflammation modulator, and, most importantly, a component of pulmonary surfactant, it may improve lung function and counteract symptoms associated with respiratory diseases, as recently evidenced in patients with COPD, COVID-19, asthma, and bronchiectasis. The aim of this review is to evaluate the potential therapeutic role of myo-inositol supplementation in the management of patients with respiratory diseases. Full article

Background/ Objectives: Long COVID or post-acute sequelae of SARS-CoV-2 infection (PASC) are symptoms that manifest despite passing the acute infection phase. These manifestations encompass a wide range of symptoms, the most common being fatigue, shortness of breath, and cognitive dysfunction. Genetic predisposition is clearly involved in the susceptibility of individuals to developing these persistent symptoms and the variation in the severity and forms. This review summarizes the role of genetic factors and gene polymorphisms in the development of major pulmonary vascular disorders associated with long COVID. Methods: A comprehensive review of current literature was conducted to examine the genetic contributions to pulmonary complications following SARS-CoV-2 infection. Studies investigating genetic polymorphisms linked to pulmonary hypertension, pulmonary thromboembolism, and pulmonary vascular endothelialitis were reviewed and summarized. Results: Findings show that specific genetic variants contribute to increased susceptibility to pulmonary vascular complications in long COVID patients. Variants associated with endothelial dysfunction, coagulation pathways, and inflammatory responses have been implicated in the development of pulmonary hypertension and thromboembolic events. Genetic predispositions influencing vascular integrity and immune responses appear to influence disease severity and progression. Conclusions: Understanding these mechanisms and genetic predispositions could pave the way for targeted therapeutic interventions to alleviate the burden on patients experiencing long COVID. Full article